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We present the case of a 51-year-old patient with acute pericarditis as the dominant manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.,The patient was admitted to the emergency department during a coronavirus disease 2019 (COVID-19) outbreak with a suspected ST-elevation myocardial infarction.,A coronary angiogram was normal.,Real-time reverse transcriptase PCR for the detection of nucleic acid from SARS-CoV-2 in a nasopharyngeal swab was positive.,Laboratory tests revealed an increased white blood cell count, with neutrophilia and lymphocytopenia, elevated level of C-reactive protein, borderline elevated erythrocyte sedimentation rate, and slightly elevated interleukin 6.,Echocardiography showed a hyperechogenic pericardium posterolaterally with minimal localized pericardial effusion.,A chest computed tomography scan showed a small zone of ground-glass opacity in the right lower lobe (classified as CO-RADS 3).,In patients with chest pain, ST elevation on electrocardiogram, a normal coronary angiogram, and suspected COVID-19, we should think of pericarditis as an unusual presentation of SARS-CoV-2 infection.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients.,Diabetes mellitus (DM) is considered an independent risk factor for the development of CAD.,Metformin, an anti-diabetic drug, has been shown in pre-clinical and clinical studies, to lower the cardiovascular events in the DM patients.,Growing evidence suggests that metformin has a protective effect on coronary artery beyond its hypoglycemic effects.,Given its global availability, route of administration and cost, metformin provides an alternate/additional therapeutic option for primary and secondary prevention of CAD in DM and non-diabetics alike.,Future prospective cohort-based studies and randomized clinical trials are needed to identify ‘at-risk’ population who may potentially benefit from metformin.

Metformin is the most-prescribed oral medication to lower blood glucose worldwide.,Yet previous systematic reviews have raised doubts about its effectiveness in reducing risk of cardiovascular disease, the most costly complication of type 2 diabetes.,We aimed to systematically identify and pool randomised trials reporting cardiovascular outcomes in which the effect of metformin was ‘isolated’ through comparison to diet, lifestyle or placebo.,We performed an electronic literature search of MEDLINE, EMBASE and the Cochrane Library.,We also manually screened the reference lists of previous meta-analyses of trials of metformin identified through a MEDLINE search.,We included randomised controlled trials of adults with type 2 diabetes comparing any dose and preparation of oral metformin with no intervention, placebo or a lifestyle intervention and reporting mortality or a cardiovascular outcome.,We included ten articles reporting 13 trials (including a total of 2079 individuals with type 2 diabetes allocated to metformin and a similar number to comparison groups) of which only four compared metformin with placebo and collected data on cardiovascular outcomes.,Participants were mainly white, aged ≤65 years, overweight/obese and with poor glycaemic control.,Summary estimates were based on a small number of events: 416 myocardial infarctions/ischaemic heart disease events in seven studies and 111 strokes in four studies.,The UK Prospective Diabetes Study (UKPDS) contributed the majority of data to the summary estimates, with weights ranging from 52.3% for myocardial infarction to 70.5% for stroke.,All outcomes, with the exception of stroke, favoured metformin, with limited heterogeneity between studies, but none achieved statistical significance.,Effect sizes (Mantel-Haenszel RR) were: all-cause mortality 0.96 (95% CI 0.84, 1.09); cardiovascular death 0.97 (95% CI 0.80, 1.16); myocardial infarction 0.89 (95% CI 0.75, 1.06); stroke 1.04 (95% CI 0.73, 1.48); and peripheral vascular disease 0.81 (95% CI 0.50, 1.31).,There remains uncertainty about whether metformin reduces risk of cardiovascular disease among patients with type 2 diabetes, for whom it is the recommended first-line drug.,Although this is mainly due to absence of evidence, it is unlikely that a definitive placebo-controlled cardiovascular endpoint trial among people with diabetes will be forthcoming.,Alternative approaches to reduce the uncertainty include the use of electronic health records in long-term pragmatic evaluations, inclusion of metformin in factorial trials, publication of cardiovascular outcome data from adverse event reporting in trials of metformin and a cardiovascular endpoint trial of metformin among people without diabetes.,The online version of this article (doi:10.1007/s00125-017-4337-9) contains a slideset of the figures for download, which is available to authorised users.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Thrombotic complications associated with coronavirus disease 2019 (COVID-19) have been described; these have mainly included venous thromboembolic events.,Limited literature is available regarding arterial thrombosis.,Acute limb ischemia is associated with severe complications that can result in significant morbidity and mortality.,Herein, we report 3 cases of COVID-19 infection complicated by arterial thrombosis in the form of acute limb ischemia.,Our case series adds to the limited literature regarding arterial thrombosis.

Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate.,Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported.,The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone.,To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19.,We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center.,Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions.,We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms.,Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms.,All patients were treated with intravenous hydration and anticoagulation.,None suffered hemorrhagic complications, and all were discharged home.,We identified 12 other patients with CVST in the setting of COVID-19 via literature search.,There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%).,During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications.,The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.

While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse.,We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients.,In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19.,Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded.,Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA.,The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001).,In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively].,In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002).,PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.,Graphical Abstract

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development.,A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers.,The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored.,Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes.,Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts.,Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries.,Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status.,The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.

Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD).,However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified.,This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability.,Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM).,Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status.,Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07).,A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95% CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: −4.09, −2.55).,Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values.,In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

Emerging evidence shows that severe coronavirus disease 2019 (COVID‐19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism.,The incidence of venous thromboembolism among COVID‐19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions.,D‐dimer might help in early recognition of these high‐risk patients and also predict outcome.,Preliminary data show that in patients with severe COVID‐19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis‐induced coagulopathy criteria or with markedly elevated d‐dimer.,Recent recommendations suggest that all hospitalized COVID‐19 patients should receive thromboprophylaxis, or full therapeutic‐intensity anticoagulation if such an indication is present.

There is an increased attention to stroke following SARS-CoV-2.,The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients.,This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand).,The outcome was the risk of subsequent stroke.,Centres were included by non-probability sampling.,The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol.,Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test.,The risk of subsequent stroke was estimated through meta-analyses with random effect models.,Bivariate logistic regression was used to determine the parameters with predictive outcome value.,The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines.,We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020.,A total of 17,799 patients were included in meta-analyses.,Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis.,Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures.,The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke.,The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%).,The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients.,None.

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19).,We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units.,Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic).,The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model.,Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation.,We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis.,All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses.,Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%).,The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%).,Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively.,With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.,The online version of this article (10.1007/s11239-020-02235-z) contains supplementary material, which is available to authorized users.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries.,Nevertheless, there is no single useful marker existing for predicting CAL of KD.,Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL.,Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase.,PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications.,Finally, eight eligible studies were included.,The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78-0.89) and 0.71 (95% CI: 0.68-0.75), respectively.,The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531.,Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73-0.89) and 0.72 (95% CI: 0.68-0.76), respectively.,SROC was 0.8868 ± 0.0486.,This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD.,We register this study with PROSPERO (CRD42019130083).

Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication.,The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities.,Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children.,Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA.,Unfortunately, 10-20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment.,Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases.,Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA.,Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur.,These complications are most likely to arise in the largest, so-called giant CAA.,Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself.,Conclusion: Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA.,Since children with previous KD are entering adulthood, long-term follow-up is increasingly important.What is known:• Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication.,• Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood.What is new:• In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway.,• As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects.,Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats.,Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each.,Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days.,The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose.,The blood samples were taken 24 h after the last dose of ISO.,The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups.,All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP.,All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment.,CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI.,MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC.,CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination.,Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.

Total flavonoid extract from Dracocephalum moldavica L.,(TFDM) contains effective components of D. moldavica L. that have myocardial protective function.,However, the cardioprotection function of TFDM is undesirable due to its poor solubility.,In order to improve the solubility and efficacy of TFDM, we developed TFDM-loaded solid lipid nanoparticles (TFDM-SLNs) and optimized the formulation of TFDM-SLNs using central composite design and response surface methodology.,The physicochemical properties of TFDM-SLNs were characterized, and the pharmacodynamics was investigated using the myocardial ischemia-reperfusion injury model in rats.,The nanoparticles of optimal formulation for TFDM-SLNs were spherical in shape with the average particle size of 104.83 nm and had a uniform size distribution with the polydispersity index value of 0.201.,TFDM-SLNs also had a negative zeta potential of −28.7 mV to ensure the stability of the TFDM-SLNs emulsion system.,The results of pharmacodynamics demonstrated that both TFDM and TFDM-SLN groups afforded myocardial protection, and the protective effect of TFDM-SLNs was significantly superior to that of TFDM alone, based on the infarct area, histopathological examination, cardiac enzyme levels and inflammatory factors in serum.,Due to the optimal quality and the better myocardial protective effect, TFDM-SLNs are expected to become a safe and effective nanocarrier for the oral delivery of TFDM.

Atherosclerosis is the process underlying heart attack and stroke.,A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core.,Pro-phagocytic antibody-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells; however, these therapies can cause off-target clearance of healthy tissues, leading to toxicities such as anemia.,Here, we developed a macrophage-specific nanotherapy based on single-walled carbon nanotubes (SWNTs) loaded with a chemical inhibitor of the anti-phagocytic CD47-SIRPαsignaling axis.,We demonstrate that these SWNTs accumulate within the atherosclerotic plaque, reactivate lesional phagocytosis, and reduce plaque burden in atheroprone apoE−/− mice without compromising safety, thereby overcoming a key translational barrier for this class of drugs.,Single-cell RNA sequencing analysis reveals that pro-phagocytic SWNTs decrease the expression of inflammatory genes linked to cytokine and chemokine pathways in lesional macrophages, demonstrating the potential of Trojan horse nanoparticles to prevent atherosclerotic cardiovascular disease.

Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis.,The current treatment of atherosclerosis by pharmacotherapy has limited therapeutic efficacy.,Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs).,The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release.,Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation.,The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis.,Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.,Due to poor specificity, the current pharmacotherapy of atherosclerosis has limited therapeutic efficacy.,Here, the authors show that a macrophage-biomimetic nanomedicine effectively alleviates atherosclerosis via targeted pharmacotherapy and sequestration of proinflammatory cytokines and chemokines.

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection.,Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients.,In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications.,These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure.,Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19).,Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin.,These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes.,We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy.,Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity.,We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs.,Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients.

Several comorbidities have been associated with an increased risk of severity and mortality in coronavirus disease 2019 (COVID-19), including hypertension, diabetes, cerebrovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease.,In this systematic review and meta-analysis, we attempted to investigate the association between heart failure (HF) and poor outcome in patients with COVID-19.,We performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, “Heart failure” and “COVID-19”.,The outcome of interest was mortality and poor prognosis (defined by incidence of severe COVID-19 infection, admission to ICU, and use of ventilator) in patients with preexisting heart failure with coronavirus disease.,We identified 204 potential articles from our search, and 22 duplicates were removed.,After screening of the titles and abstracts of the remaining 182 articles we identified 92 potentially relevant articles.,We excluded 74 studies due to the following reasons: four studies were systematic reviews, two studies were meta-analyses, three articles were literature reviews, and 65 articles did not report on the outcome of interest.,Finally, we included the remaining 18 studies in our qualitative synthesis and meta-analysis.,There were 21,640 patients from 18 studies.,HF was associated with hospitalization in COVID19 HR was 2.37 [1.48, 3.79; p < 0.001], high heterogeneity [I2, 82%; p < 0.001].,HF was associated with a poor outcome demonstrated by an OR of 2.86 [2.07; 3.95; p < 0.001] high heterogeneity [I2, 80%; p < 0.001].,Patient with preexisting HF was associated with higher mortality OR of 3.46 [2.52, 4.75; p < 0.001] moderately high heterogeneity [I2, 77%; p < 0.001].,Patients with heart failure are at increased risk for hospitalization, poor outcome, and death from COVID-19.,A significant difference in mortality between patients with and without heart failure was observed, patients with heart failure having a higher mortality.

•Cerebrovascular disease was associated with mortality and severity of COVID-19 (borderline).,•Cardiovascular disease was associated with mortality and severity of COVID-19.,•Gender, age, hypertension, diabetes, and respiratory comorbidities did not influence the associations•The association between cerebrovascular disease and poor outcome in COVID-19 was not affected by cardiovascular diseases and vice versa .,Cerebrovascular disease was associated with mortality and severity of COVID-19 (borderline).,Cardiovascular disease was associated with mortality and severity of COVID-19.,Gender, age, hypertension, diabetes, and respiratory comorbidities did not influence the associations,The association between cerebrovascular disease and poor outcome in COVID-19 was not affected by cardiovascular diseases and vice versa .,We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia.,A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database.,The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19.,A total of 4448 patients were obtained from 16 studies.,Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%).,Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%).,Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%).,Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities.,Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa.,Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.

Editor’s Note.-Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics.,Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.,Articles in this section are published solely online and are linked to the original article.

There is increasing evidence supporting coronavirus disease 2019 (COVID-19)-related coagulopathy.,In the available literature, only 2 cases of superior mesenteric vein thrombosis have been described.,We present a peculiar case of high-grade small bowel obstruction in a patient with COVID-19 infection.,Exploratory laparotomy revealed a congenital adhesion band with associated focal bowel ischemia contributed by superior mesenteric vein thrombosis and positive lupus anticoagulant.,It is important to consider the rare differential of mesenteric vein thrombosis and its related sequelae of mesenteric ischemia in a patient with COVID-19 who presents with abdominal pain.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality.,The mechanisms underlying this prothrombotic state remain enigmatic.,Further data to guide anticoagulation strategies are urgently required.,We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients.,Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found.,Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications.,Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction.,The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy.,The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management.,In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue.,However, substantive differences exist between these guidelines which can be difficult for clinicians.,This review briefly summarizes the major societal guidelines and compares their similarities and differences.,A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.

The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death.,While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis.,Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death.,Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis.,At present, the pathophysiology underlying the hypercoagulable state is poorly understood.,However, a growing body of data suggests that the initial events occur in the lung.,A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy.,This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis.,Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies.,Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.,•COVID-19 generates a significantly increased risk for thrombosis•Pulmonary inflammation and localized vasculopathy are central to the hypercoagulable state•Immune dysregulation is notable in severe illness•Rising D-dimer levels correlate with worse outcomes•Anticoagulant guidelines are rapidly evolving as we gather further insights,COVID-19 generates a significantly increased risk for thrombosis,Pulmonary inflammation and localized vasculopathy are central to the hypercoagulable state,Immune dysregulation is notable in severe illness,Rising D-dimer levels correlate with worse outcomes,Anticoagulant guidelines are rapidly evolving as we gather further insights

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also referred to as COVID-19, was declared a pandemic by the World Health Organization in March 2020.,The manifestations of COVID-19 are widely variable and range from asymptomatic infection to multi-organ failure and death.,Like other viral illnesses, acute myocarditis has been reported to be associated with COVID-19 infection.,However, guidelines for the diagnosis of COVID-19 myocarditis have not been established.,Using a combination of search terms in the PubMed/Medline, Ovid Medline and the Cochrane Library databases and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with COVID-19 infection.,Fourteen records comprising a total of fourteen cases that report myocarditis/myopericarditis secondary to COVID-19 infection were identified.,There was a male predominance (58%), with the median age of the cases described being 50.4 years.,The majority of patients did not have a previously identified comorbid condition (50%), but of those with a past medical history, hypertension was most prevalent (33%).,Electrocardiogram findings were variable, and troponin was elevated in 91% of cases.,Echocardiography was performed in 83% of cases reduced function was identified in 60%.,Endotracheal intubation was performed in the majority of cases.,Glucocorticoids were most commonly used in treatment of myocarditis (58%).,Majority of patients survived to discharge (81%) and 85% of those that received steroids survived to discharge.,Guidelines for diagnosis and management of COVID-19 myocarditis have not been established and our knowledge on management is rapidly changing.,The use of glucocorticoids and other agents including IL-6 inhibitors, IVIG and colchicine in COVID-19 myocarditis is debatable.,In our review, there appears to be favorable outcomes related to myocarditis treated with steroid therapy.,However, until larger scale studies are conducted, treatment approaches have to be made on an individualized case-by-case basis.

The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.,An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020.,Data reported are those available through May 6, 2020.,A multicenter study including three Indianapolis area academic hospitals.,Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals.,One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.,All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.,The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development.,Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019.,Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism.,Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.,One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care.,The mean (± sd) age was 61 ± 16 years and 57% were male.,Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died.,Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital.,Elevated admission d-dimer and peak d-dimer were associated with venous thromboembolism development (p < 0.05). d-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%.,Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study.,The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.,These data show that coronavirus disease 2019 results in a hypercoagulable state.,Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.

The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.,An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020.,Data reported are those available through May 6, 2020.,A multicenter study including three Indianapolis area academic hospitals.,Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals.,One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.,All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.,The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development.,Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019.,Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism.,Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.,One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care.,The mean (± sd) age was 61 ± 16 years and 57% were male.,Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died.,Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital.,Elevated admission d-dimer and peak d-dimer were associated with venous thromboembolism development (p < 0.05). d-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%.,Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study.,The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.,These data show that coronavirus disease 2019 results in a hypercoagulable state.,Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.

Vaccine-associated cerebral venous thrombosis has become an issue following the extensive vaccination program of the Coronavirus Disease of 2019 (COVID-19) Vaccine AstraZeneca (ChAdOx1 vaccine).,The importance of early diagnosis should be emphasized due to the high mortality rate without appropriate treatment.,Young female populations in western countries have been reported to be at a greater risk of this vaccine related thrombotic event, but cases in East Asia are lacking.,Herein, we present the first case of cerebral venous sinus thrombosis 10 days after ChAdOx1 vaccination in a middle-age Asian male in Taiwan.

Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca).,More data were needed on the pathogenesis of this unusual clotting disorder.,We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.,We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions.,Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.,Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49).,Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage.,Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died.,Five patients had disseminated intravascular coagulation.,None of the patients had received heparin before symptom onset.,All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin.,Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter).,Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.,Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia.,(Funded by the German Research Foundation.)

Infection with SARS-CoV-2 (COVID-19) can cause prothrombotic complications.,We aim to study the frequency of thrombotic complications and impact of anticoagulation on outcomes in hospitalized patients.,We conducted a retrospective chart review of 921 consecutive patients admitted to our hospital with COVID-19.,Patients were divided into four groups depending on whether they were on anticoagulation prior to admission, started anticoagulation during the admission, received prophylactic anticoagulation, or did not receive any anticoagulation.,At the time of analysis, 325 patients (35.3%) had died, while 544 patients (59%) had been discharged resulting in inpatient mortality of 37.3%.,Male sex, age > 65 years, and high D-dimer at admission were associated with higher mortality.,Sixteen patients (1.7%) had venous thromboembolism confirmed with imaging, 11 patients had a stroke, and 2 patients developed limb ischemia.,Treatment with therapeutic anticoagulation was associated with improved inpatient mortality compared with prophylactic anticoagulation alone (63% vs 86.2%, p < 0.0001) in patients requiring mechanical ventilation.,Other outcomes such as rates of liberation from mechanical ventilation and duration of mechanical ventilation were not significantly impacted by the type of anticoagulation.,The online version of this article (10.1007/s00277-020-04216-x) contains supplementary material, which is available to authorized users.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000.,The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.,Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.,Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020.,Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.,Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male.,Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]).,Hypertension, diabetes, and coronary heart disease were the most common comorbidities.,Notably, 81.2% of patients had very low eosinophil counts on admission.,Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others.,Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments.,A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.,Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases.,The majority of the patients died of multiple organ failure.,Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations.,Eosinophilopenia may indicate a poor prognosis.,A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

There are concerns that public anxiety around COVID‐19 discourages patients from seeking medical help.,The aim of this study was to see how lockdown due to the pandemic affected the number of admissions of acute stroke.,All patients discharged from Akershus University Hospital with a diagnosis of transient ischemic attack (TIA) or acute stroke were identified by hospital chart review.,January 3 to March 12 was defined as before, and March 13 to April 30 as during lockdown.,There were 21.8 admissions/week before and 15.0 admissions/week during the lockdown (P < .01).,Patients had on average higher NIHSS during the lockdown than before (5.9 vs.,4.2, P = .041).,In the multivariable logistic regression model for ischemic stroke (adjusted for sex, age, living alone and NIHSS ≤ 5), there was an increased OR of 2.05 (95% CI 1.10‐3.83, P = .024) for not reaching hospital within 4.5 hours during the lockdown as compared to the period before the lockdown.,There was a significant reduction in number of admissions for stroke and TIAs during the lockdown due to the COVID‐19 pandemic in Norway.

The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease.,SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion.,MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside.,CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure.,Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved.,Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process.,SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI.,PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia.,MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion.,Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia.,In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions.,In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality.,Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease.,In this Consensus Statement, the authors summarize the use of SPECT, PET, MRI, echocardiography, CT and invasive coronary flow and pressure measurement, and describe the relative strengths and weaknesses of each modality.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction.,Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs.,Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP).,Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches.,MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease.,Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening.,•Cardiac fibroblasts and endothelial cells induce hiPSC-cardiomyocyte maturation•CX43 gap junctions form between cardiac fibroblasts and cardiomyocytes•cAMP-pathway activation contributes to hiPSC-cardiomyocyte maturation•Patient-derived hiPSC-cardiac fibroblasts cause arrhythmia in microtissues,Cardiac fibroblasts and endothelial cells induce hiPSC-cardiomyocyte maturation,CX43 gap junctions form between cardiac fibroblasts and cardiomyocytes,cAMP-pathway activation contributes to hiPSC-cardiomyocyte maturation,Patient-derived hiPSC-cardiac fibroblasts cause arrhythmia in microtissues,Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues.,Cardiomyocytes matured structurally and functionally.,Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy.,Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.

To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches.,Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes.,Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ~0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization.,These results demonstrate the utility of hiPSCCMs to detect drug-induced proarrhythmic effects as part of the evolving Comprehensive In Vitro Proarrhythmia Assay paradigm.

The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain.,We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.,We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group.,Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded.,Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK).,We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg).,The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat.,Data for 344 716 participants from 48 randomised clinical trials were available for this analysis.,Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988).,There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg.,The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction.,After a median 4·15 years' follow-up (Q1-Q3 2·97-4·96), 42 324 participants (12·3%) had at least one major cardiovascular event.,In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3-32·5) in the comparator group and 25·9 (25·4-26·4) in the intervention group.,In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0-40·5) and 36·0 (95% CI 35·3-36·7), in the comparator and intervention groups, respectively.,Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89-0·94 for partipants without previous cardiovascular disease and 0·89, 0·86-0·92, for those with previous cardiovascular disease.,In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories.,In this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high-normal blood pressure values.,These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment.,Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself.,British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19).,Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors.,There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells.,However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19.,Therefore, antihypertensive therapy with these agents should be continued.,In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury.,Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification.,Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being.,For the ongoing management of patients with hypertension, telemedicine‐based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained.,Overall, multidisciplinary management of COVID‐19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis.,However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data.,This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19.,We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization.,Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization.,A total of 305 patients were included.,Mean age was 63 years and 205 patients (67.2%) were male.,Overall, myocardial injury was observed in 190 patients (62.3%).,Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions.,Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.,Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities.,Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury.,Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world - this is the most recent and alarming update.,COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure.,Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death.,To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease.,Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body.,The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2).,Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects.,Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD.,This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients.,In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization.,We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.,Unlabelled Image,•COVID-19 patients with underlying CVD have drastically increased risks of mortality.,•SARS-CoV2 uses ACE2 as cell entry receptor.,•Current and novel COVID-19 drugs may act on the SARS-CoV-2 receptor ACE2.,•ACE-I and ARB may interfere with COVID-19 susceptibility and effects on the heart.,COVID-19 patients with underlying CVD have drastically increased risks of mortality.,SARS-CoV2 uses ACE2 as cell entry receptor.,Current and novel COVID-19 drugs may act on the SARS-CoV-2 receptor ACE2.,ACE-I and ARB may interfere with COVID-19 susceptibility and effects on the heart.

Risk factors for pulmonary embolism in patients with coronavirus disease 2019 include obesity, an elevated d-dimer value, elevated C-reactive protein level, and a rising d-dimer value over time.

This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit in France with severe coronavirus disease 2019 (COVID-19).

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected.,Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered.,Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19.,A key role may be that of the renin-angiotensin-aldosterone system.,Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti‐inflammatory effects.,Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19.,On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers.,ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation.,Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity.,Prospective trials are needed to ascertain whether these drugs may have protective effects.

SARS-CoV-2 infection is associated with hypercoagulability which predisposes to venous thromboembolism (VTE).,We analyzed platelet and neutrophil activation in COVID-19 patients and their association with VTE.,Hospitalized COVID-19 patients and age- and sex-matched healthy controls were studied.,Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase-9 (MMP-9), a neutrophil-released enzyme, were measured.,Four patients were re-studied after recovery.,The activating effect of COVID-19 plasma on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied.,36 COVID-19 patients and 31 healthy controls were studied; 8/36 COVID-19 patients (22.2%) developed VTE.,Platelets and neutrophils were activated in COVID-19 patients.,NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis.,Plasmatic MMP-9 was significantly increased in COVID-19 patients.,Platelet and neutrophil activation markers, but less so NETs, normalized after recovery.,In vitro, plasma from COVID-19 patients triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic dose low-molecular weight heparin, but not by aspirin or dypiridamole.,Platelet and neutrophil activation are key features of COVID-19 patients.,NET biomarkers may help to predict clinical worsening and VTE, and may guide LMWH-treatment intensity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy.,Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response.,The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.,This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands.,With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020.,In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course.,Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78).,Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days).,In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course.,Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract.,In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain.,In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata.,Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]).,Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets..,In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs.,However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19.,This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19.,Amsterdam UMC Corona Research Fund.

Adverse cardiac remodeling after myocardial infarction (MI) is associated with extremely high mortality rates worldwide.,Although optimized medical therapy, Preservation of lusitropic and inotropic function and protection against adverse remodeling in ventricular structure remain relatively frequent.,This study demonstrated that Andrographolide (Andr) significantly ameliorated adverse cardiac remodeling induced by myocardial infarction and improves contractile function in mice with LAD ligation compared with the control group.,Briefly, Andr markedly attenuated cardiac fibrosis and relieved inflammation after myocardial infarction.,Specifically, Andr significantly blocked oxidative stress and the nuclear translocation of p-P65 following myocardial infarction.,At the mechanistic level, antioxidant effect of Andr was achieved through strengthening antioxidative stress capacity and attributed to the activation of Nrf2/HO-1 Signaling.,Consistently, H9C2 administrated with Andr showed a decreased oxidative stress caused by hypoxia precondition, but treatment with specific Nrf2 inhibitor (ML385) or the silence of Nrf2 blunted the activation of Nrf2/HO-1 Signaling and removed the protective effects of Andr in vitro.,Thus, we suggest that Andr alleviates adverse cardiac remodeling following myocardial infarction through enhancing Nrf2 signaling pathway.

Intracerebral hemorrhage (ICH) induces potently oxidative stress responses and inflammatory processes.,Isoliquiritigenin (ILG) is a flavonoid with a chalcone structure and can activate nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant system, negatively regulate nuclear factor-κB (NF-κB) and nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways, but its role and potential molecular mechanisms in the pathology following ICH remain unclear.,The present study aimed to explore the effects of ILG after ICH and underlying mechanisms.,ICH model was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male Sprague-Dawley rats weighing 280-320 g.,Different doses of ILG (10, 20, or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling, respectively.,Rats were intracerebroventricularly administrated with control scramble small interfering RNA (siRNA) or Nrf2 siRNA at 24 h before ICH induction, and after 24 h, ICH model was established with or without ILG (20 mg/kg) treatment.,All rats were dedicated at 24 or 72 h after ICH.,Neurological deficits, histological damages, brain water content (BWC), blood-brain barrier (BBB) disruption, and neuronal degeneration were evaluated; quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry/immunofluorescence, western blot, and enzyme-linked immunosorbent assay (ELISA) were carried out; catalase, superoxide dismutase activities and reactive oxygen species (ROS), and glutathione/oxidized glutathione contents were measured.,ILG (20 and 40 mg/kg) markedly alleviated neurological deficits, histological damages, BBB disruption, brain edema, and neuronal degeneration, but there was no significant difference between two dosages.,ILG (20 mg/kg) significantly suppressed the NF-κB and NLRP3 inflammasome pathways and activated Nrf2-mediated antioxidant system.,Gene silencing of Nrf2 aggravated the neurological deficits, brain edema, and neuronal degeneration and increased the protein levels of NF-κB p65, NLRP3 inflammasome components, and IL-1β.,ILG delivery significantly attenuated the effects of Nrf2 siRNA interference mentioned above.,Intraperitoneal administration of ILG after ICH reduced early brain impairments and neurological deficits, and the mechanisms were involved in the regulation of ROS and/or NF-κB on the activation of NLRP3 inflammasome pathway by the triggering of Nrf2 activity and Nrf2-induced antioxidant system.,In addition, our experimental results may make ILG a potential candidate for a novel therapeutical strategy for ICH.,The online version of this article (doi:10.1186/s12974-017-0895-5) contains supplementary material, which is available to authorized users.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

To present guidance for clinicians caring for adult patients with acuteischemic stroke with confirmed or suspected COVID-19 infection.,The summary was prepared after review of systematic literature reviews,reference to previously published stroke guidelines, personal files, and expert opinionby members from 18 countries.,The document includes practice implications for evaluation of stroke patientswith caution for stroke team members to avoid COVID-19 exposure, during clinicalevaluation and conduction of imaging and laboratory procedures with specialconsiderations of intravenous thrombolysis and mechanical thrombectomy in strokepatients with suspected or confirmed COVID-19 infection.,Conclusions-The summary is expected to guide clinicians caring for adult patientswith acute ischemic stroke who are suspected of, or confirmed, with COVID-19infection.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can lead to severe pneumonia, but also thrombotic complications and non‐pulmonary organ failure.,Recent studies suggest intravascular neutrophil activation and subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of coronavirus disease 2019 (COVID‐19).,We sought to study whether immunothrombosis is a pathognomonic factor in COVID‐19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation.,By comparing histopathological specimens of SARS‐CoV‐2 with influenza‐affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID‐19, but less prominent in influenza pneumonia.,Activated neutrophils were typically found in physical association with monocytes.,To explore this further, we combined clinical data of COVID‐19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA‐seq data.,We show that a HLADRlow CD9low monocyte population expands in severe COVID‐19, which releases neutrophil chemokines in the lungs, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID‐19.,Our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS‐CoV‐2 infection.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients.,Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19.,A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations.,An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome.,Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases.,In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure.,Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain.,Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare.,Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected.,Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases.,Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders.,Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19.,This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed.,With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.

Initial reports suggest a significant risk of thrombotic events, including stroke, in patients hospitalized with coronavirus disease 2019 (COVID-19).,However, there is little systematic data on stroke incidence and mechanisms, particularly in racially diverse populations in the United States.,We performed a retrospective, observational study of stroke incidence and mechanisms in all patients with COVID-19 hospitalized from March 15 to May 3, 2020, at 3 Philadelphia hospitals.,We identified 844 hospitalized patients with COVID-19 (mean age 59 years, 52% female, 68% Black); 20 (2.4%) had confirmed ischemic stroke; and 8 (0.9%) had intracranial hemorrhage.,Of the ischemic stroke patients, mean age was 64 years, with only one patient (5%) under age 50, and 80% were Black.,Conventional vascular risk factors were common, with 95% of patients having a history of hypertension and 60% a history of diabetes mellitus.,Median time from onset of COVID symptoms to stroke diagnosis was 21 days.,Stroke mechanism was cardioembolism in 40%, small vessel disease in 5%, other determined mechanism in 20%, and cryptogenic in 35%.,Of the 11 patients with complete vascular imaging, 3 (27%) had large vessel occlusion.,Newly positive antiphospholipid antibodies were present in >75% of tested patients.,Of the patients with intracranial hemorrhage, 5/8 (63%) were lobar intraparenchymal hemorrhages, and 3/8 (38%) were subarachnoid hemorrhage; 4/8 (50%) were on extracorporeal membrane oxygenation.,We found a low risk of acute cerebrovascular events in patients hospitalized with COVID-19.,Most patients with ischemic stroke had conventional vascular risk factors, and traditional stroke mechanisms were common.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca).,More data were needed on the pathogenesis of this unusual clotting disorder.,We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19.,We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions.,Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.,Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49).,Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage.,Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died.,Five patients had disseminated intravascular coagulation.,None of the patients had received heparin before symptom onset.,All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin.,Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter).,Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation.,Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia.,(Funded by the German Research Foundation.)

Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).,To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.,We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network.,The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715).,The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism.,Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White.,Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common.,Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting.,Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all).,Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis.

In response to myocardial infarction (MI), neutrophils (PMNs) are early responders that initiate the inflammatory reaction.,Because macrophages and fibroblasts show polarization states after MI, we hypothesized PMNs also undergo phenotypic changes over the MI time course.,The objective of the current study was to map the continuum of polarization phenotypes in cardiac neutrophils over the first week of MI.,C57BL/6J male mice (3-6 months old) underwent permanent coronary artery ligation to induce MI, and PMNs were isolated from the infarct region at days 1, 3, 5, and 7 after MI.,Day 0 served as a no MI negative control.,Aptamer proteomics was performed on biological replicates (n = 10-12) for each time point.,Day (D)1 MI neutrophils had a high degranulation profile with increased matrix metalloproteinase (MMP) activity.,D3 MI neutrophil profiles showed upregulation of apoptosis and induction of extracellular matrix (ECM) organization.,D5 MI neutrophils further increased their ECM reorganization profile.,D7 MI neutrophils had a reparative signature that included expression of fibronectin, galectin-3, and fibrinogen to contribute to scar formation by stimulating ECM reorganization.,Of note, fibronectin was a key modulator of degranulation, as it amplified MMP-9 release in the presence of an inflammatory stimulus.,Our results indicate that neutrophils selectively degranulate over the MI time course, reflective of both their intrinsic protein profiles as well as the ECM environment in which they reside.,MMPs, cathepsins, and ECM proteins were prominent neutrophil degranulation indicators.,The online version of this article (10.1007/s00395-019-0746-x) contains supplementary material, which is available to authorized users.

Macrophages promote both injury and repair following myocardial infarction, but discriminating functions within mixed populations remains challenging.,Here we used fate mapping and single-cell transcriptomics to demonstrate that at steady state, TIMD4+LYVE1+MHC-IIloCCR2− resident cardiac macrophages self-renew with negligible blood monocyte input.,Monocytes partially replaced resident TIMD4−LYVE1−MHC-IIhiCCR2− macrophages and fully replaced TIMD4−LYVE1−MHC-IIhiCCR2+ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets.,Ischemic injury reduced TIMD4+ and TIMD4− resident macrophage abundance within infarcted tissue while recruited, CCR2+ monocyte-derived macrophages adopted multiple cell fates, including those nearly indistinguishable from resident macrophages.,Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, highlighting a non-redundant, cardioprotective role of resident cardiac macrophages.,Lastly, we demonstrate the ability of TIMD4 to be used as a durable lineage marker of a subset of resident cardiac macrophages.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

Sprouty1 (Spry1) is a negative modulator of receptor tyrosine kinase signaling, but its role in cardiomyocyte survival has not been elucidated.,The aim of this study was to investigate the potential role of cardiomyocyte Spry1 in cardiac ischemia-reperfusion (I/R) injury.,Infarct areas of mouse hearts showed an increase in Spry1 protein expression, which localized to cardiomyocytes.,To investigate if cardiomyocyte Spry1 regulates I/R injury, 8-week-old inducible cardiomyocyte Spry1 knockout (Spry1 cKO) mice and control mice were subjected to cardiac I/R injury.,Spry1 cKO mice showed reduction in release of cardiac troponin I and reduced infarct size after I/R injury compared to control mice.,Similar to Spry1 knockdown in cardiomyocytes in vivo, RNAi-mediated Spry1 silencing in isolated cardiomyocytes improved cardiomyocyte survival following simulated ischemia injury.,Mechanistically, Spry1 knockdown induced cardiomyocyte extracellular signal-regulated kinase (ERK) phosphorylation in healthy hearts and isolated cardiomyocytes, and enhanced ERK phosphorylation after I/R injury.,Spry1-deficient cardiomyocytes showed better preserved mitochondrial membrane potential following ischemic injury and an increase in levels of phosphorylated ERK and phosphorylated glycogen synthase kinase-3β (GSK-3β) in mitochondria of hypoxic cardiomyocytes.,Overexpression of constitutively active GSK-3β abrogated the protective effect of Spry1 knockdown.,Moreover, pharmacological inhibition of GSK-3β protected wild-type cardiomyocytes from cell death, but did not further protect Spry1-silenced cardiomyocytes from hypoxia-induced injury.,Cardiomyocyte Spry1 knockdown promotes ERK phosphorylation and offers protection from I/R injury.,Our findings indicate that Spry1 is an important regulator of cardiomyocyte viability during ischemia-reperfusion injury.,The online version of this article (10.1007/s00395-018-0713-y) contains supplementary material, which is available to authorized users.

Disturbed mitochondrial homeostasis contributes to the pathogenesis of cardiac ischemia reperfusion (IR) injury, although the underlying mechanism remains elusive.,Here, we demonstrated that casein kinase 2α (CK2α) was upregulated following acute cardiac IR injury.,Increased CK2α was shown to be instrumental to mitochondrial damage, cardiomyocyte death, infarction area expansion and cardiac dysfunction, whereas cardiac-specific CK2α knockout (CK2αCKO) mice were protected against IR injury and mitochondrial damage.,Functional assay indicated that CK2α enhanced the phosphorylation (inactivation) of FUN14 domain containing 1 (FUNDC1) via post-transcriptional modification at Ser13, thus effectively inhibiting mitophagy.,Defective mitophagy failed to remove damaged mitochondria induced by IR injury, resulting in mitochondrial genome collapse, electron transport chain complex (ETC) inhibition, mitochondrial biogenesis arrest, cardiolipin oxidation, oxidative stress, mPTP opening, mitochondrial debris accumulation and eventually mitochondrial apoptosis.,In contrast, loss of CK2α reversed the FUNDC1-mediated mitophagy, providing a survival advantage to myocardial tissue following IR stress.,Interestingly, mice deficient in both CK2α and FUNDC1 failed to show protection against IR injury and mitochondrial damage through a mechanism possible attributed to lack of mitophagy.,Taken together, our results confirmed that CK2α serves as a negative regulator of mitochondrial homeostasis via suppression of FUNDC1-required mitophagy, favoring the development of cardiac IR injury.

Hypertension can originate from early-life adverse environmental in utero exposure to dexamethasone (DEX) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).,Since DEX and TCDD are related to the aryl hydrocarbon receptor (AHR) signaling pathway, we examined whether resveratrol, an AHR modulator and antioxidant, could prevent programmed hypertension via regulating AHR signaling and oxidative stress.,Groups of four-month-old male rat offspring were studied (n = 7-8 per group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), TCDD (200 ng/kg in four once-weekly oral doses), DEX + TCDD, and DEX + TCDD + R (resveratrol 0.05% in drinking water throughout pregnancy and lactation).,Maternal TCDD exposure aggravated prenatal DEX-induced hypertension in adult male offspring, which maternal resveratrol therapy prevented.,Maternal TCDD exposure aggravated DEX-induced oxidative damage in offspring kidneys, which was prevented by resveratrol therapy.,Maternal resveratrol therapy decreased asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, thereby preventing combined DEX and TCDD exposure-induced programmed hypertension.,Increases in renal Ahrr and Cyp1a1 expression induced by DEX + TCDD exposure were restored by resveratrol therapy.,The beneficial effects of resveratrol on DEX + TCDD-induced hypertension relate to reduced renal mRNA expression of Ren, Ace, and Agtr1a expression.,Thus, the beneficial effects of resveratrol on DEX + TCDD-induced hypertension include reduction of oxidative stress, restoration of nitric oxide (NO) bioavailability, blockade of the renin-angiotensin system (RAS), and antagonizing AHR signaling pathway.

Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and oxidative stress are closely related to the development of hypertension.,Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) regulates oxidative stress.,Dimethyl fumarate (DMF) reportedly activates Nrf2 and protects against oxidative stress damage.,We examined a 4-month-old male rat offspring from five groups (n = 8 for each group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), HF (D12331 diet from weaning to 4 months of age), and DEX + HF, DEX + HF + DMF (50 mg/kg/day via gastric gavage for 3 weeks after weaning).,We found that postnatal HF intake aggravated prenatal DEX-induced hypertension in adult male offspring, which could be prevented by DMF treatment.,The beneficial effects of DMF treatment include an increase in renal Nrf2 gene expression, reduction of oxidative stress, decrease in plasma asymmetric dimethylarginine (ADMA) and renal soluble epoxide hydrolase protein levels, increase in the l-arginine-to-ADMA ratio, and activation of genes related to nutrient sensing and autophagy (e.g., Pparb, Pparg, Ppargc1a, Ulk1, and Atg5).,In conclusion, better understanding of the impact of the Nrf2 signaling pathway in the two-hit model will aid in protecting children exposed to antenatal corticosteroids and a postnatal HF diet from programmed hypertension.

Venous thromboembolic events have been one of the main causes of mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia.,The aim of our study was to describe the prevalence of deep vein thrombosis (DVT) in noncritically ill patients with COVID-19 pneumonia and correlate such observations with the thromboprophylaxis received.,We performed a prospective cohort study of 67 patients admitted to the hospital for COVID-19 pneumonia.,The diagnosis was confirmed using polymerase chain reaction testing of nasopharyngeal specimens.,The deep veins were examined using compression duplex ultrasonography with the transducer on B-mode.,The patients were separated into two groups for statistical analysis: those receiving low-molecular-weight heparin prophylaxis and those receiving intermediate or complete anticoagulation treatment.,Risk analysis and logistic regression were performed.,Of the 67 patients, 57 were included in the present study after applying the inclusion and exclusion criteria; 49.1% were women, and the patient mean age was 71.3 years.,All 57 patients had undergone compression duplex ultrasonography.,Of these 57 patients, 6 were diagnosed with DVT, for an in-hospital rate of DVT in patients with COVID-19 pneumonia of 10.5%.,All the patients who had presented with DVT had been receiving low-molecular-weight heparin prophylaxis.,The patients receiving prophylactic anticoagulation treatment had a greater risk of DVT (16.21%; 95% confidence interval, 0.04-0.28; P = .056) compared with those receiving intermediate or complete anticoagulation treatment.,We also found a protective factor for DVT in the intermediate or complete anticoagulation treatment group (odds ratio, 0.19; 95% confidence interval, 0.08-0.46; P < .05).,Noncritically ill, hospitalized patients with COVID-19 pneumonia have a high risk of DVT despite receipt of correct, standard thromboprophylaxis.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

Na pandemia pela COVID-19, o aumento da ocorrência e da mortalidade por doenças cardiovasculares (DCV) vem sendo reconhecido no mundo.,No Brasil, é essencial que o impacto da COVID-19 na DCV seja analisado.,Avaliar o impacto desta pandemia nos números de internações hospitalares (IH), óbitos hospitalares (OH) e letalidade intra-hospitalar (LH) por DCV a partir de dados epidemiológicos do Sistema Único de Saúde (SUS).,Estudo observacional de séries temporais por meio da análise comparativa das taxas de IH, OH e LH por DCV registrados entre janeiro e maio de 2020, usando como referência os valores obtidos no mesmo período entre 2016 e 2019 e os valores projetados por métodos de regressão linear para o ano de 2020.,O nível significância estatística utilizado foi de 0,05.,Em comparação com o mesmo período de 2019, houve um decréscimo de 15% na taxa de IH e de 9% no total de OH por DCV entre março e maio de 2020, acompanhado de um aumento de 9% na taxa de LH por esse grupo de doenças, sobretudo entre pacientes com idade de 20-59 anos.,As taxas de IH e LH registradas em 2020 diferiram significativamente da tendência projetada para o corrente ano (p=0,0005 e 0,0318, respectivamente).,Durante os primeiros meses da pandemia, observou-se um declínio na IH associado a um aumento da LH por DCV no Brasil.,Esses dados possivelmente são consequência do planejamento inadequado no manejo das DCV durante a pandemia, sendo necessária a implementação de ações imediatas para modificar esse cenário.,(Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0),In the COVID-19 pandemic, the increase in the incidence of cardiovascular diseases (CVD) and mortality from them has been recognized worldwide.,In Brazil, the impact of COVID-19 on CVD must be evaluated.,To assess the impact of the current pandemic on the numbers of hospital admissions (HA), in-hospital deaths (ID), and in-hospital fatality (IF) from CVD by use of national epidemiological data from the Brazilian Unified Public Health System.,Time-series observational study using comparative analysis of the HA, ID, and IF due to CVD recorded from January to May 2020, having as reference the values registered in the same period from 2016 to 2019 and the values projected by linear regression methods for 2020.,The statistical significance level applied was 0.05.,Compared to the same period in 2019, there was a 15% decrease in the HA rate and a 9% decrease in the total ID due to CVD between March and May 2020, followed by a 9% increase in the IF rate due to CVD, especially among patients aged 20-59 years.,The HA and IF rates registered in 2020 differed significantly from the projected trend for 2020 (p = 0.0005 and 0.0318, respectively).,During the first months of the pandemic, there were a decline in HA and an increase in IF due to CVD in Brazil.,These data might have resulted from the inadequate planning of the CVD management during the pandemic.,Thus, immediate actions are required to change this scenario.,(Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.,Lancet (London, England) 395(10229):1054-62, 2020).,While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection.,J Am Coll Surg (2020).,Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study.,Ann Intensive Care 9(1):19, 2019).,We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test.,Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371).,All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded.,The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission.,Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection.,Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9).,Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 109/L), respectively.,Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased.,There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score.,In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels.,We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists.,This hypothesis should be confirmed by future studies.

COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

Supplemental Digital Content is available in the text.,High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality.,While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension.,We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP.,A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm Hg for neutrophil counts; all P<10-50).,Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings.,These inverse-variance weighted estimates were consistent with other robust MR methods.,The exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses.,MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils.,Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio.,Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP.

There are limited data on the nighttime blood pressure (BP)-lowering effect of esaxerenone and its effect on N-terminal pro b-type natriuretic peptide (NT-proBNP), a predictor of cardiovascular risk, according to different dipping patterns of nocturnal BP.,This was a post hoc analysis of a multicenter, open-label, long-term phase 3 study of esaxerenone, a new highly selective mineralocorticoid receptor blocker, in patients with essential hypertension.,Patients were classified by dipping pattern (extreme dippers, dippers, non-dippers, risers).,Mean changes in BP, changes in dipping pattern, mean NT-proBNP levels, and percentage of patients with normal NT-proBNP levels (<55 pg/mL) at baseline and Weeks 12 and 28 were evaluated.,Nighttime systolic BP decreased in all dipping pattern groups at Week 28, with the riser group showing the greatest change (−25.5 mmHg).,A significant shift in dipping pattern and riser/non-dipper pattern changes to dipper/extreme dipper pattern were found from baseline to Week 28 (p < 0.0001).,The prevalence of the riser pattern decreased from 14.4% to 9.8%, and that of the non-dipper pattern from 44.7% to 39.2%.,The decrease in NT-proBNP from baseline to Week 28 was statistically significant in risers, non-dippers, dippers, and extreme dippers (p < 0.001, respectively).,At baseline, the proportion of patients with NT-proBNP <55 pg/mL was lowest in risers versus the other dipping pattern types, but after reductions in NT-proBNP in all groups to Week 28, these differences disappeared.,Long-term administration of esaxerenone may be a useful treatment option for nocturnal hypertension, especially in patients with a riser pattern.

To systematically analyse the effect of pharmacological treatment of hypertension (HTN) on cognitive decline in older adults.,Randomised, placebo-controlled trials with a prespecified quantitative outcome of cognition and a pharmacological intervention for at least 12 months to treat HTN in older adults (>60 years).,Our primary outcome was change in cognition with pharmacological treatment of HTN.,Standardised mean difference (SMD) was used to analyse different outcomes reported in the selected studies.,We searched PubMed CENTRAL and the Cochrane Library from inception to 6 July 2020.,Two independent reviewers assessed trial quality and extracted data.,Internal and external validity of the studies was assessed.,Nine randomised controlled trials with 34 994 participants were included in the final analysis.,The net SMD for change in cognition was −0.049 (CI: −0.078 to −0.019) indicating that treatment of HTN decreased cognitive decline.,Heterogeneity was low with an I² of 6%.,Current evidence does not indicate worsening of cognition with treatment of HTN.,Treatment of HTN in older adults may reduce cognitive decline.,These results have important implications in clinical management of patients at risk for dementia.,CRD42020139750.

Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19).,We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19.,From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis.,Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis.,We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users.,Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005).,For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904).,Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002).,We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.

The SARS‐CoV‐2 virus binds to the angiotensin‐converting enzyme 2 (ACE2) receptor for cell entry.,It has been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID‐19 infection.,We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID‐19 at two hospitals with a multi‐ethnic catchment population in London (UK).,The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity.,Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset.,A total of 399 patients (33.3%) were taking ACEi or ARB.,Patients on ACEi/ARB were significantly older and had more comorbidities.,The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).,There was no evidence for increased severity of COVID‐19 in hospitalised patients on chronic treatment with ACEi or ARB.,A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials.

The current COVID-19 crisis has significantly impacted healthcare systems worldwide.,There has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions.,Complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic.,We present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting COVID-19 in the hospital.,Moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like ST-segment elevation myocardial infarction (STEMI).,We emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of STEMI during this current era of COVID-19 pandemic.

The COVID-19 pandemic has dramatically changed the practice medicine on a global scale during the year 2020.,With fewer patients presenting to hospitals with the diagnosis of STEMI, healthcare workers are wondering what is causing this decline.,This piece presents data from two medical centers and addresses several possible causes to explain this phenomenon.,It was found that there was a statistically significant decrease from January to March 2020 in number of presenting STEMI diagnoses.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is the first class of anti-diabetes treatment that reduces mortality and risk for hospitalization due to heart failure.,In clinical studies it has been shown that SGLT2i’s promote a general shift to fasting state metabolism characterized by reduced body weight and blood glucose, increase in glucagon/insulin ratio and modest increase in blood ketone levels.,Therefore, we investigated the connection between metabolic changes and cardiovascular function in the ob/ob−/− mice; a rodent model of early diabetes with specific focus on coronary microvascular function.,Due to leptin deficiency these mice develop metabolic syndrome/diabetes and hepatic steatosis.,They also develop cardiac contractile and microvascular dysfunction and are thus a promising model for translational studies of cardiometabolic diseases.,We investigated whether this mouse model responded in a human-like manner to empagliflozin treatment in terms of metabolic parameters and tested the hypothesis that it could exert direct effects on coronary microvascular function and contractile performance.,Lean, ob/ob−/− untreated and ob/ob−/− treated with SGLT2i were followed for 10 weeks.,Coronary flow velocity reserve (CFVR) and fractional area change (FAC) were monitored with non-invasive Doppler ultrasound imaging.,Food intake, urinary glucose excursion and glucose control via HbA1c measurements were followed throughout the study.,Liver steatosis was assessed by histology and metabolic parameters determined at the end of the study.,Sodium-glucose cotransporter 2 inhibitors treatment of ob/ob−/− animals resulted in a switch to a more catabolic state as observed in clinical studies: blood cholesterol and HbA1c were decreased whereas glucagon/insulin ratio and ketone levels were increased.,SGLT2i treatment reduced liver triglyceride, steatosis and alanine aminotransferase, an indicator for liver dysfunction. l-Arginine/ADMA ratio, a marker for endothelial function was increased.,SGLT2i treatment improved both cardiac contractile function and coronary microvascular function as indicated by improvement of FAC and CFVR, respectively.,Sodium-glucose cotransporter 2 inhibitors treatment of ob/ob−/− mice mimics major clinical findings regarding metabolism and cardiovascular improvements and is thus a useful translational model.,We demonstrate that SGLT2 inhibition improves coronary microvascular function and contractile performance, two measures with strong predictive values in humans for CV outcome, alongside with the known metabolic changes in a preclinical model for prediabetes and heart failure.

Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes.,Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM).,The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes.,The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF) rats.,Male ZDF rats were used as a model of T2DM (35 diabetic ZDF‐Leprfa/fa and 16 ZDF-Lepr+/+ controls).,Empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 6 weeks.,Treatment with empagliflozin restored glycemic control.,Empagliflozin improved endothelial function (thoracic aorta) and reduced oxidative stress in the aorta and in blood of diabetic rats.,Inflammation and glucotoxicity (AGE/RAGE signaling) were epigenetically prevented by SGLT2i treatment (ChIP).,Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP) were positively correlated with HbA1c.,Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i.,Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia.,Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial).,fx1,•Hyperglycemia induces vascular complications and cardiovascular disease.,•Empagliflozin reduces hyperglycemia and cardiovascular mortality (EMPA-REG trial).,•Here, empagliflozin normalized vascular function and oxidative stress in ZDF rats.,•Here, empagliflozin reduced AGE/RAGE signaling, inflammation and oxidative stress.,•Here, empagliflozin conferred glycemic control, epigenetic and pleiotropic effects.,Hyperglycemia induces vascular complications and cardiovascular disease.,Empagliflozin reduces hyperglycemia and cardiovascular mortality (EMPA-REG trial).,Here, empagliflozin normalized vascular function and oxidative stress in ZDF rats.,Here, empagliflozin reduced AGE/RAGE signaling, inflammation and oxidative stress.,Here, empagliflozin conferred glycemic control, epigenetic and pleiotropic effects.

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease.,The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies.,The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards.,A systematic literature search and a critical review of the collected studies were conducted.,An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed.,We found 28 scientific papers; the total amount of cases is 341.,The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels.,It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed.,A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed.,In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

Galectin-3 is a member of the galectin family, which are β-galactoside-binding lectins with ≥1 evolutionary conserved carbohydrate-recognition domain.,It binds proteins in a carbohydrate-dependent and -independent manner.,Galectin-3 is predominantly located in the cytoplasm; however, it shuttles into the nucleus and is secreted onto the cell surface and into biological fluids including serum and urine.,It serves important functions in numerous biological activities including cell growth, apoptosis, pre-mRNA splicing, differentiation, transformation, angiogenesis, inflammation, fibrosis and host defense.,Numerous previous studies have indicated that galectin-3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer.,With emerging evidence to support the function and application of galectin-3, the current review aims to summarize the latest literature regarding the biomarker characteristics and potential therapeutic application of galectin-3 in associated diseases.

In this review, we highlight the most important cellular and molecular mechanisms that contribute to cardiac inflammation and fibrosis.,We also discuss the interplay between inflammation and fibrosis in various precursors of heart failure (HF) and how such mechanisms can contribute to myocardial tissue remodelling and development of HF.,Recently, many research articles attempt to elucidate different aspects of the interplay between inflammation and fibrosis.,Cardiac inflammation and fibrosis are major pathophysiological mechanisms operating in the failing heart, regardless of HF aetiology.,Currently, novel therapeutic options are available or are being developed to treat HF and these are discussed in this review.,A progressive disease needs an aggressive management; however, existing therapies against HF are insufficient.,There is a dynamic interplay between inflammation and fibrosis in various precursors of HF such as myocardial infarction (MI), myocarditis and hypertension, and also in HF itself.,There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF.,Understanding and describing the elements of the inflammatory and fibrotic pathways are essential, and specific drugs that target these pathways need to be evaluated.

This study aimed to evaluate the impact of coronavirus disease 2019 (Covid‐19) outbreak on admissions for acute myocardial infarction (AMI) and related mortality, severity of presentation, major cardiac complications and outcome in a tertiary‐care university hospital in Berlin, Germany.,In a single‐centre cross‐sectional observational study, we included 355 patients with AMI containing ST‐elevation or non‐ST‐elevation myocardial infarction (STEMI or NSTEMI), admitted for emergency cardiac catheterization between January and April 2020 and the equivalent time in 2019.,During the early phase of the Covid‐19 pandemic (e‐COV) in Berlin (March and April 2020), admissions for AMI halved compared with those in the pre‐Covid‐19 time (January and February 2020; pre‐COV) and with those in the corresponding months in 2019.,However, mortality for AMI increased substantially from 5.2% pre‐COV to 17.7% (P < 0.05) during e‐COV.,Severity of presentation for AMI was more pronounced during e‐COV [increased levels of cardiac enzymes, reduced left ventricular ejection fraction (LVEF), an increase in the need of inotropic support by 25% (P < 0.01)], while patients' demographic and angiographic characteristics did not differ between pre‐COV and e‐COV.,Time from symptom onset to first medical contact was prolonged in all AMI during e‐COV (presentation > 72 h +21% in STEMI, p = 0.04 and presentation > 72 h in NSTEMI +22%, p = 0.02).,Door to balloon time was similar in STEMI patients, while time from first medical contact to revascularization was significantly delayed in NSTEMI patients (p = 0.02).,Major cardiac complications after AMI occurred significantly more often, and cardiac recovery was worse in e‐COV than in pre‐COV, demonstrated by a significantly lower LVEF (39 ± 16 vs. 46 ± 16, p < 0.05) at hospital discharge and substantially higher NTproBNP levels.,The Covid‐19 outbreak affects hospital admissions for acute coronary syndromes.,During the first phase of the pandemia, significantly less patients with AMI were admitted, but those admitted presented with a more severe phenotype and had a higher mortality, more complications, and a worse short‐term outcome.,Therefore, our data indicate that Covid‐19 had relevant impact on non‐infectious disease states, such as acute coronary syndromes.

During the COVID-19 pandemic, excess mortality has been reported, while hospitalisations for acute cardiovascular events reduced.,Brazil is the second country with more deaths due to COVID-19.,We aimed to evaluate excess cardiovascular mortality during COVID-19 pandemic in 6 Brazilian capital cities.,Using the Civil Registry public database, we evaluated total and cardiovascular excess deaths, further stratified in specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular deaths in the 6 Brazilian cities with greater number of COVID-19 deaths (São Paulo, Rio de Janeiro, Fortaleza, Recife, Belém, Manaus).,We compared observed with expected deaths from epidemiological weeks 12-22 of 2020.,We also compared the number of hospital and home deaths during the period.,There were 65 449 deaths and 17 877 COVID-19 deaths in the studied period and cities for 2020.,Cardiovascular mortality increased in most cities, with greater magnitude in the Northern capitals.,However, while there was a reduction in specified cardiovascular deaths in the most cities, the Northern capitals showed an increase of these events.,For unspecified cardiovascular deaths, there was a marked increase in all cities, which strongly correlated to the rise in home deaths (r=0.86, p=0.01).,Excess cardiovascular mortality was greater in the less developed cities, possibly associated with healthcare collapse.,Specified cardiovascular deaths decreased in the most developed cities, in parallel with an increase in unspecified cardiovascular and home deaths, presumably as a result of misdiagnosis.,Conversely, specified cardiovascular deaths increased in cities with a healthcare collapse.

Amyloidosis is caused by dysregulation of protein folding resulting in systemic or organ specific amyloid aggregation.,When affecting the heart, amyloidosis can cause severe heart failure, which is associated with a high morbidity and mortality.,Different subtypes of cardiac amyloidosis exist e.g. transthyretin cardiac amyloidosis and senile cardiac amyloidosis.,Today, diagnostics is primarily based on cardiac biopsies and no clinically used circulating blood-based biomarkers existing.,Therefore, our aim was to identify circulating microRNAs in patients with different forms of amyloidosis.,Blood was collected from healthy subjects (n = 10), patients with reduced ejection fraction (EF < 35%; n = 10), patients affected by transthyretin cardiac amyloidosis (n = 13) as well as senile cardiac amyloidosis (n = 11).,After performing TaqMan array profiling, promising candidates, in particular miR-99a-5p, miR-122-5p, miR-27a-3p, miR-221-3p, miR-1180-3p, miR-155-5p, miR-339-3p, miR-574-3p, miR-342-3p and miR-329-3p were validated via quantitative real time PCR.,The validation experiments revealed a significant upregulation of miR-339-3p in patients affected with senile cardiac amyloidosis compared to controls.,This corresponded to the array profiling results.,In contrast, there was no deregulation in the other patient groups.,MiR-339-3p was increased in blood of patients with senile cardiac amyloidosis.,Therefore, miR-339-3p is a potential candidate as biomarker for senile cardiac amyloidosis in future studies.,Larger patient cohorts should be investigated.

Circulating miRNAs are proposed as a biomarker of heart disease.,This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM).,A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12).,The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing.,After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated.,Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16).,A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects.,Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM.,Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction.,This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Supplemental Digital Content is available in the text.,Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce.,We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection.,One hundred consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared with reference values.,Echocardiographic studies included left ventricular (LV) systolic and diastolic function and valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound.,A second examination was performed in case of clinical deterioration.,Thirty-two patients (32%) had a normal echocardiogram at baseline.,The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%).,Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared with patients with normal troponin or better clinical condition, but they had worse RV function.,Clinical deterioration occurred in 20% of patients.,In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients).,Femoral deep vein thrombosis was diagnosed in 5 of 12 patients with RV failure.,In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic function and RV function are impaired.,Elevated troponin and poorer clinical grade are associated with worse RV function.,In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without deep vein thrombosis, is more common, but acute LV systolic dysfunction was noted in ≈20%.

What is the burden of multiple myeloma globally and by country, how has it changed over time, and how widely available are treatments for this disease?,Myeloma incident cases and deaths increased from 1990 to 2016, with middle-income countries contributing the most to this increase.,Treatment availability is very limited in countries with low socioeconomic development.,Marked variation in myeloma incidence and mortality across countries highlights the need to improve access to diagnosis and effective therapy and to expand research on etiological determinants of myeloma.,Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality.,A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care.,To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016.,We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study.,Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates.,We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region.,We collected data on approval of lenalidomide and bortezomib worldwide.,Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year.,Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3).,Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles.,The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe.,Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016.,Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East.,In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively.,Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries.,Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa.,Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient.,Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence.,This systematic analysis reports incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study to characterize the burden of multiple myeloma and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016.

We studied the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in younger individuals, age 10-49 years, using samples from the National Health and Nutritional Examination Survey (NHANES) III.,NHANES prevalence rates were standardized to the 2000 US total population.,Among 12 372 individuals (4073 blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified in 63 persons (0.34%, 95% CI 0.23-0.50).,The prevalence of MGUS was significantly higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI 0.11-0.45), P=0.001.,The prevalence of MGUS in Mexican-Americans was at an intermediate level (0.41%, 95% CI 0.23-0.73).,The disparity in prevalence of MGUS between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI 2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013.,There was a trend to earlier age of onset of MGUS in blacks compared with whites.,MGUS was seen in only two persons in the 10-19 age-group (both Mexican-American), and in three persons in the 20-29-year age-group (all of whom were black).,In persons less than 50 years of age, MGUS is significantly more prevalent, with up to 10 years earlier age of onset, in blacks compared with whites.

Atherosclerosis is the process underlying heart attack and stroke.,A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core.,Pro-phagocytic antibody-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells; however, these therapies can cause off-target clearance of healthy tissues, leading to toxicities such as anemia.,Here, we developed a macrophage-specific nanotherapy based on single-walled carbon nanotubes (SWNTs) loaded with a chemical inhibitor of the anti-phagocytic CD47-SIRPαsignaling axis.,We demonstrate that these SWNTs accumulate within the atherosclerotic plaque, reactivate lesional phagocytosis, and reduce plaque burden in atheroprone apoE−/− mice without compromising safety, thereby overcoming a key translational barrier for this class of drugs.,Single-cell RNA sequencing analysis reveals that pro-phagocytic SWNTs decrease the expression of inflammatory genes linked to cytokine and chemokine pathways in lesional macrophages, demonstrating the potential of Trojan horse nanoparticles to prevent atherosclerotic cardiovascular disease.

Cardiovascular diseases are the leading cause of death worldwide.,Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation.,Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease.,This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools.,We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.

Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).,Myocardial injury caused by COVID-19 was previously reported in hospitalized patients.,It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.,Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included.,CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping).,Edema ratio and LGE were assessed in post-COVID-19 patients.,Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.,Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients.,Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings.,Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs.,38.1 ms ± 2.4 vs.,39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs.,24.8% [23.1% to 25.4%] vs.,23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).,Cardiac involvement was found in a proportion of patients recovered from COVID-19.,CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function.,Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.

To generate novel rabbit models with a large-fragment deletion of either LDL receptor (LDLR) and/or apolipoprotein (apoE) genes for the study of hyperlipidemic and atherosclerosis.,CRISPR/Cas9 system directed by a multiple sgRNAs system was used in rabbit embryos to edit their LDLR and apoE genes.,The LDLR and apoE genes of founder rabbits were sequenced, and their plasma lipids and lipoprotein profiles on a normal chow diet were analyzed, western blotting was also performed to evaluate the expression of apolipoprotein.,Sudan IV and HE staining of aortic were performed to confirm the formation of atherosclerosis.,Six knockout (KO) rabbits by injection of both LDLR and apoE sgRNAs were obtained, including four LDLR KO rabbits and two LDLR/apoE double- KO rabbits.,Sequence analysis of these KO rabbits revealed that they contained multiple mutations including indels, deletions, and substitutions, as well as two rabbit lines containing biallelic large fragment deletion in the LDLR region.,Analysis of their plasma lipids and lipoprotein profiles of these rabbits fed on a normal chow diet revealed that all of these KO rabbits exhibited remarkable hyperlipidemia with total cholesterol levels increased by up to 10-fold over those of wild-type rabbits.,Pathological examinations of two founder rabbits showed that KO rabbits developed prominent aortic and coronary atherosclerosis.,Large fragment deletions can be achieved in rabbits using Cas9 mRNA and multiple sgRNAs.,LDLR KO along with LDLR/apoE double KO rabbits should provide a novel means for translational investigations of human hyperlipidemia and atherosclerosis.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease caused mainly by LDL receptor (Ldlr) gene mutations.,Unlike FH patients, heterozygous Ldlr knockout (KO) mice do not show a dominant FH trait.,Hamsters, like humans, have the cholesteryl ester transfer protein, intestine-only ApoB editing and low hepatic cholesterol synthesis.,Here, we generated Ldlr-ablated hamsters using CRISPR/Cas9 technology.,Homozygous Ldlr KO hamsters on a chow diet developed hypercholesterolemia with LDL as the dominant lipoprotein and spontaneous atherosclerosis.,On a high-cholesterol/high-fat (HCHF) diet, these animals exhibited severe hyperlipidemia and atherosclerotic lesions in the aorta and coronary arteries.,Moreover, the heterozygous Ldlr KO hamsters on a short-term HCHF diet also had overt hypercholesterolemia, which could be effectively ameliorated with several lipid-lowering drugs.,Importantly, heterozygotes on 3-month HCHF diets developed accelerated lesions in the aortas and coronary arteries.,Our findings demonstrate that the Ldlr KO hamster is an animal model of choice for human FH and has great potential in translational research of hyperlipidemia and coronary heart disease.,•Ldlr knockout hamsters were successfully generated by using the CRISPR/Cas9 editing system.,•Loss of one copy of the Ldlr gene predisposes hamsters to diet-induced hyperlipidemia and coronary atherosclerosis.,•Heterozygous Ldlr KO hamsters differentially respond to different lipid-lowering drugs.,•Homozygous Ldlr KO hamsters on a chow diet develop severe hypercholesterolemia and spontaneous atherosclerosis.,Ldlr knockout hamsters were successfully generated by using the CRISPR/Cas9 editing system.,Loss of one copy of the Ldlr gene predisposes hamsters to diet-induced hyperlipidemia and coronary atherosclerosis.,Heterozygous Ldlr KO hamsters differentially respond to different lipid-lowering drugs.,Homozygous Ldlr KO hamsters on a chow diet develop severe hypercholesterolemia and spontaneous atherosclerosis.,Genetically engineered animal models, especially mouse models, have been widely used to study the pathogenesis of cardiovascular disease.,However, distinct differences in the metabolic profiles of mice and humans limit further applications of mouse models toward understanding atherosclerosis in humans.,In the present study, we use the CRISPR/Cas9 editing system to delete the Ldlr gene in hamsters, a species exhibiting similar metabolic features to those of humans.,Diet-induced heterozygous Ldlr KO hamsters show hyperlipidemia with atherosclerotic lesions in both the aorta and coronary arteries, which has been observed in FH patients but not in mice.,Moreover, aged homozygous Ldlr KO hamsters on a chow diet display severe hypercholesterolemia and spontaneous atherosclerosis.,Our work explores a human-like animal model for basic and translational research of human atherosclerosis.

Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).,These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.,ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest.,The panel included 3 patient representatives.,The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020).,The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients.,The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.,The panel agreed on 2 recommendations.,The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE.,These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation.,They will be updated using a living recommendation approach as new evidence becomes available.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

The coronavirus disease 2019 pandemic has affected healthcare systems around the globe and massively impacted patients with various non-infectious, life-threatening conditions.,Stroke is a major neurological disease contributing to death and disability worldwide, and is still an ongoing issue during the pandemic.,Here we investigate the impact of the coronavirus disease 2019 outbreak on stroke manifestations, treatment courses, the outcome of stroke patients, and the hospitalization rate in a referral center for stroke management in Tehran, Iran.,We extracted data regarding 31 stroke patients (10 patients with laboratory-confirmed coronavirus disease 2019) and compared the demographic and pathological characteristics of the patients with or without coronavirus disease 2019 infection.,The association of demographic/pathological characteristics of stroke patients during the coronavirus disease 2019 pandemic and a corresponding period during the previous year (49 patients) and an earlier period during the same year as the pandemic (50 patients) was also evaluated.,The absolute number of admissions decreased about 40% during the coronavirus disease 2019 pandemic.,Except for the stroke severity (P = 0.002), there were no significant changes in the demographic and pathological characteristics of the stroke patients during the three studied periods.,A significantly higher mean of age (75.60 ± 9.54 versus 60.86 ± 18.45; P = 0.007), a significant difference in the type of stroke (P = 0.046), and significantly higher stroke severity (P = 0.024) were observed in stroke patients with coronavirus disease 2019 compared with those of stroke patients without coronavirus disease 2019.,Treatment approaches, duration of hospitalization, and mortality rates did not differ significantly.,This report shows that the pandemic caused the number of acute stroke admissions to plummet compared to other periods.,Although the pandemic did not affect the treatment plans and care of the patients, stroke cases with coronavirus disease 2019 had higher age, more large vessel ischemic stroke, and more severe stroke.,Further studies are urgently needed to realize the probable interaction of the coronavirus disease 2019 pandemic and the neurologic disease.

Emergency measures to treat patients with coronavirus 2019 (COVID-19) and contain the outbreak is the main priority in each of our hospitals; however, these measures are likely to result in collateral damage among patients with other acute diseases.,Here, we investigate whether the COVID-19 pandemic affects acute stroke care through interruptions in the stroke chain of survival.,A descriptive analysis of acute stroke care activity before and after the COVID-19 outbreak is given for a stroke network in southern Europe.,To quantify the impact of the pandemic, the number of stroke code activations, ambulance transfers, consultations through telestroke, stroke unit admissions, and reperfusion therapy times and rates are described in temporal relationship with the rising number of COVID-19 cases in the region.,Following confinement of the population, our stroke unit activity decreased sharply, with a 25% reduction in admitted cases (mean number of 58 cases every 15 days in previous months to 44 cases in the 15 days after the outbreak, P<0.001).,Consultations to the telestroke network declined from 25 every 15 days before the outbreak to 7 after the outbreak (P<0.001).,The increasing trend in the prehospital diagnosis of stroke activated by 911 calls stopped abruptly in the region, regressing to 2019 levels.,The mean number of stroke codes dispatched to hospitals decreased (78% versus 57%, P<0.001).,Time of arrival from symptoms onset to stroke units was delayed >30 minutes, reperfusion therapy cases fell, and door-to-needle time started 16 minutes later than usual.,The COVID-19 pandemic is disruptive for acute stroke pathways.,Bottlenecks in the access and delivery of patients to our secured stroke centers are among the main challenges.,It is critical to encourage patients to continue seeking emergency care if experiencing acute stroke symptoms and to ensure that emergency professionals continue to use stroke code activation and telestroke networks.

The aim of this paper was to create an updated Australian guideline on footwear for people with diabetes.,We reviewed new footwear publications, (inter)national guidelines, and consensus expert opinion alongside the 2013 Australian footwear guideline to formulate updated recommendations.,We recommend health professionals managing people with diabetes should: (1) Advise people with diabetes to wear footwear that fits, protects and accommodates the shape of their feet.,(2) Advise people with diabetes to always wear socks within their footwear, in order to reduce shear and friction.,(3) Educate people with diabetes, their relatives and caregivers on the importance of wearing appropriate footwear to prevent foot ulceration.,(4) Instruct people with diabetes at intermediate- or high-risk of foot ulceration to obtain footwear from an appropriately trained professional to ensure it fits, protects and accommodates the shape of their feet.,(5) Motivate people with diabetes at intermediate- or high-risk of foot ulceration to wear their footwear at all times, both indoors and outdoors.,(6) Motivate people with diabetes at intermediate- or high-risk of foot ulceration (or their relatives and caregivers) to check their footwear, each time before wearing, to ensure that there are no foreign objects in, or penetrating, the footwear; and check their feet, each time their footwear is removed, to ensure there are no signs of abnormal pressure, trauma or ulceration.,(7) For people with a foot deformity or pre-ulcerative lesion, consider prescribing medical grade footwear, which may include custom-made in-shoe orthoses or insoles.,(8) For people with a healed plantar foot ulcer, prescribe medical grade footwear with custom-made in-shoe orthoses or insoles with a demonstrated plantar pressure relieving effect at high-risk areas.,(9) Review prescribed footwear every three months to ensure it still fits adequately, protects, and supports the foot.,(10) For people with a plantar diabetic foot ulcer, footwear is not specifically recommended for treatment; prescribe appropriate offloading devices to heal these ulcers.,This guideline contains 10 key recommendations to guide health professionals in selecting the most appropriate footwear to meet the specific foot risk needs of an individual with diabetes.

High plantar pressures are implicated in the development of diabetes-related foot ulcers.,Whether plantar pressures remain high in patients with chronic diabetes-related foot ulcers over time is uncertain.,The primary aim of this study was to compare plantar pressures at baseline and three and six months later in participants with chronic diabetes-related foot ulcers (cases) to participants without foot ulcers (controls).,Standardised protocols were used to measure mean peak plantar pressure and pressure-time integral at 10 plantar foot sites (the hallux, toes, metatarsals 1 to 5, mid-foot, medial heel and lateral heel) during barefoot walking.,Measurements were performed at three study visits: baseline, three and six months.,Linear mixed effects random-intercept models were utilised to assess whether plantar pressures differed between cases and controls after adjusting for age, sex, body mass index, neuropathy status and follow-up time.,Standardised mean differences (Cohen’s d) were used to measure effect size.,Twenty-one cases and 69 controls started the study and 16 cases and 63 controls completed the study.,Cases had a higher mean peak plantar pressure at several foot sites including the toes (p = 0.005, Cohen’s d = 0.36) and mid-foot (p = 0.01, d = 0.36) and a higher pressure-time integral at the hallux (p<0.001, d = 0.42), metatarsal 1 (p = 0.02, d = 0.33) and mid-foot (p = 0.04, d = 0.64) compared to controls throughout follow-up.,A reduction in pressure-time integral at multiple plantar sites over time was detected in all participants (p<0.05, respectively).,Plantar pressures assessed during gait are higher in diabetes patients with chronic foot ulcers than controls at several plantar sites throughout prolonged follow-up.,Long term offloading is needed in diabetes patients with diabetes-related foot ulcers to facilitate ulcer healing.

Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide.,Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear.,A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.,Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6).,Salient information was abstracted from the medical record.,Light microscopic findings were recorded.,An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases.,Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.,Male sex was more common in the COVID-19 group (P=0.05).,Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006).,Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease.,Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004).,Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively).,SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence.,Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis.,Cases with cleared infection had variable presentations.,This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection.,COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury.,Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent.,Histological features of resolved infection are variable.,Cardiac amyloidosis may be an additional risk factor for severe disease.

Standard evaluation and management of the patient with suspected or proven cardiovascular complications of coronavirus disease-2019 (COVID-19), the disease caused by severe acute respiratory syndrome related-coronavirus-2 (SARS-CoV-2), is challenging.,Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may often suffice for such patients, but given overlap between COVID-19 and typical cardiovascular diagnoses such as heart failure and acute myocardial infarction, need frequently arises for advanced imaging techniques to assist in differential diagnosis and management.,This document provides guidance in several common scenarios among patients with confirmed or suspected COVID-19 infection and possible cardiovascular involvement, including chest discomfort with electrocardiographic changes, acute hemodynamic instability, newly recognized left ventricular dysfunction, as well as imaging during the subacute/chronic phase of COVID-19.,For each, the authors consider the role of biomarker testing to guide imaging decision-making, provide differential diagnostic considerations, and offer general suggestions regarding application of various advanced imaging techniques.

The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection.,Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease.,Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157).,At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers).,Analysis was blinded, using objective artificial intelligence analytics where available.,A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited.,Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days).,Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide).,With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal).,These were distributed equally between seropositive and seronegative individuals.,Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.

Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis.,However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data.,This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19.,We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization.,Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization.,A total of 305 patients were included.,Mean age was 63 years and 205 patients (67.2%) were male.,Overall, myocardial injury was observed in 190 patients (62.3%).,Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions.,Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.,Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities.,Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury.,Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Trimethylamine‐N‐oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation.,However, the exact mechanism is currently unclear.,Studies have established a central role of nucleotide‐binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation.,Here, we examined the potential role of the NLRP3 inflammasome in TMAO‐induced vascular inflammation in vitro and in vivo and the underlying mechanisms.,Experiments using liquid chromatography‐tandem mass spectrometry, Western blot, and fluorescent probes showed that TMAO‐induced inflammation in human umbilical vein endothelial cells (HUVECs) and aortas from ApoE−/− mice.,Moreover, TMAO promoted NLRP3 and activated caspase‐1 p20 expression and caspase‐1 activity in vitro and in vivo.,Notably, a caspase‐1 inhibitor (YVAD), an NLRP3 inhibitor (MCC950), as well as NLRP3 short interfering RNA attenuated TMAO‐induced activation of the NLRP3 inflammasome, subsequently leading to suppression of inflammation in HUVECs.,TMAO additionally stimulated reactive oxygen species (ROS) generation, in particular, mitochondrial ROS, while inhibiting manganese superoxide dismutase 2 (SOD2) activation and sirtuin 3 (SIRT3) expression in HUVECs and aortas from ApoE−/− mice.,TMAO‐induced endothelial NLRP3 inflammasome activation was ameliorated by the mitochondrial ROS scavenger Mito‐TEMPO, or SIRT3 overexpression in HUVECs.,Conversely, TMAO failed to further inhibit magnesium SOD2 and activate the NLRP3 inflammasome or induce inflammation in SIRT3 short interfering RNA-treated HUVECs and aortas from SIRT3−/− mice.,TMAO promoted vascular inflammation by activating the NLRP3 inflammasome, and the NLRP3 inflammasome activation in part was mediated through inhibition of the SIRT3‐SOD2-mitochondrial ROS signaling pathway.

Hyperhomocysteinemia (HHcy) has been shown to promote vascular inflammation and atherosclerosis, but the underlying mechanisms remain largely unknown.,The NLRP3 inflammasome has been identified as the cellular machinery responsible for activation of inflammatory processes.,In this study, we hypothesized that the activation of NLRP3 inflammasomes contributes to HHcy-induced inflammation and atherosclerosis.,ApoE−/− mice were fed regular chow, high-fat (HF) diet, or HF plus high methionine diet to induce HHcy.,To assess the role of NLRP3 inflammasomes in HHcy-aggravated atherosclerosis, NLRP3 shRNA viral suspension was injected via tail vein to knock down the NLRP3 gene.,Increased plasma levels of IL-1β and IL-18, aggravated macrophage infiltration into atherosclerotic lesions, and accelerated development of atherosclerosis were detected in HHcy mice as compared with control mice, and were associated with the activation of NLRP3 inflammasomes.,Silencing the NLRP3 gene significantly suppressed NLRP3 inflammasome activation, reduced plasma levels of proinflammatory cytokines, attenuated macrophage infiltration and improved HHcy-induced atherosclerosis.,We also examined the effect of homocysteine (Hcy) on NLRP3 inflammasome activation in THP-1-differentiated macrophages in the presence or absence of NLRP3 siRNA or the caspase-1 inhibitor Z-WEHD-FMK.,We found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1β and IL-18 in macrophages, which were blocked by NLRP3 gene silencing or Z-WEHD-FMK.,As reactive oxygen species (ROS) may have a central role in NLRP3 inflammasome activation, we next investigated whether antioxidant N-acetyl-l-cysteine (NAC) prevented Hcy-induced NLRP3 inflammasome activation in macrophages.,We found Hcy-induced NLRP3 inflammasome activation was abolished by NAC.,Treatment with NAC in HHcy mice also suppressed NLRP3 inflammasome activation and improved HHcy-induced atherosclerosis.,These data suggest that the activation of NLRP3 inflammasomes contributes to HHcy-aggravated inflammation and atherosclerosis in apoE−/− mice.,Hcy activates NLRP3 inflammasomes in ROS-dependent pathway in macrophages.,These results may have implication for the treatment of HHcy-associated cardiovascular diseases.

Cardiovascular disease is the leading cause of morbidity and mortality in the Western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle.,Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular diseases, and therefore represent a significant medical and socioeconomic burden on our society.,It may not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them.,These intersecting points are manifested in clinical studies in which lipid lowering therapies reduce blood pressure, and anti-hypertensive medications reduce atherosclerotic plaque.,At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal Angiotensin II (Ang II).,Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis.,Therefore, VSMCs are the fulcrum in progression of these diseases and, therefore, understanding the effects of atherogenic stimuli and Ang II on the VSMC is key to understanding and treating atherosclerosis and hypertension.,In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.

Inflammation is a key mechanism of cardiovascular diseases.,It is an essential component of atherosclerosis and a significant risk factor for the development of cardiovascular events.,In the crosstalk between inflammation and cardiovascular diseases, the transcription factor NFκB seems to be a key player since it is involved in the development and progression of both inflammation and cardiac and vascular damage.,In this review, we deal with the recent findings of the role of inflammation in cardiac diseases, focusing, in particular, on NFκB as a functional link.,We describe strategies for the therapeutic targeting of NFκB as a potential strategy for the failing heart.

The aim of this study was to characterize the echocardiographic phenotype of patients with COVID-19 pneumonia and its relation to biomarkers.,Seventy-four patients (59 ± 13 years old, 78% male) admitted with COVID-19 were included after referral for transthoracic echocardiography as part of routine care.,A level 1 British Society of Echocardiography transthoracic echocardiography was used to assess chamber size and function, valvular disease, and likelihood of pulmonary hypertension.,The chief abnormalities were right ventricle (RV) dilatation (41%) and RV dysfunction (27%).,RV impairment was associated with increased D-dimer and C-reactive protein levels.,In contrast, left ventricular function was hyperdynamic or normal in most (89%) patients.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients.,However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19.,In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up.,In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist.,The primary outcome was symptomatic VTE within 45 days of hospital discharge.,Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit.,Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE.,Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%-0.6%; n = 3).,There was no evidence of acute respiratory distress syndrome (ARDS) in these patients.,Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9).,We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge.,Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit.,Randomized trials may be warranted.,•In a large multi-center study, the incidence of venous thromboembolism in COVID-19 patients followed for 45 days after hospitalization was relatively low.,•Routine extended thromboprophylaxis in COVID-19 patients who have been discharged from the hospital may not have a net clinical benefit.,•Older age, history of recent cancer, and history of recent diabetes were associated with higher risk of mortality after hospital discharge,In a large multi-center study, the incidence of venous thromboembolism in COVID-19 patients followed for 45 days after hospitalization was relatively low.,Routine extended thromboprophylaxis in COVID-19 patients who have been discharged from the hospital may not have a net clinical benefit.,Older age, history of recent cancer, and history of recent diabetes were associated with higher risk of mortality after hospital discharge

To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19).,Multicenter cohort study.,Intensive care units at 68 geographically diverse hospitals across the United States.,Critically ill adults (age ≥18 years) with laboratory confirmed covid-19.,In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality.,Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation.,Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest.,Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years).,The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status.,Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older.,Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course.,Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths.,In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany.,Our evaluation provides a systematic overview of the first 80 consecutive full autopsies.,A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19).,In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab.,In the other 74 cases, SARS-CoV-2 infection had already been known antemortem.,The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years).,In the study cohort, 34 deceased were female (38%) and 46 male (62%).,Overall, 38% of the deceased were overweight or obese.,All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus.,A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3.,Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death.,In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism.,Peripheral pulmonary artery embolisms were found in nine other cases.,Overall, deep vein thrombosis has been found in 40% of the cases.,This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

We report the case of a healthy 35‐year‐old woman who had experienced a flu‐like syndrome during the week before childbirth and heart failure symptoms 10 days before the current hospitalization and presented to our emergency department with clinical signs of congestive heart failure, echocardiographic evidence of a severely dilated and hypokinetic heart, laboratory evidence of SARS‐CoV‐2 disease, and radiologic findings consistent with both virus‐related pneumonia and heart failure.,Early cardiac magnetic resonance was crucial for the diagnosis of postpartum cardiomyopathy and for the exclusion of virus‐related myocarditis, allowing us to decide on a prudent and supportive clinical approach.

Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS).,We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE).,A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue.,He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%).,Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates.,Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6.,Renal function was normal but lactate levels were elevated.,Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated.,Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC.,His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120.,He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation.,Infusion of milrinone failed to improve his cardiogenic shock (day-1).,Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies.,Over 5 days he received daily TPE (each lasting 4 hours).,His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors.,His inflammation markers improved, and he was extubated on day-7.,RT-PCR was negative on day-17.,He was discharged to home isolation in good condition.,Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS.,If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers.,We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).,This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM.,Lymphodepletion was performed using cyclophosphamide 300 mg/m2.,LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions.,The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.,At data cutoff, 57 patients had received LCAR-B38M CAR T cells.,All patients experienced ≥ 1 adverse events (AEs).,Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%).,Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases.,One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity.,The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response.,Minimal residual disease was negative for 36/57 (63%) patients.,The median time to response was 1 month (range, 0.4 to 3.5).,At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable).,Median overall survival for all patients was not reached.,LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.,ClinicalTrials.gov, NCT03090659; Registered on March 27, 2017, retrospectively registered,The online version of this article (10.1186/s13045-018-0681-6) contains supplementary material, which is available to authorized users.

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM).,Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies.,However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use.,B cell maturation antigen (BCMA), a transmembrane glycoprotein in the tumor necrosis factor receptor superfamily 17 (TNFRSF17), is expressed at significantly higher levels in all patient MM cells but not on other normal tissues except normal plasma cells.,Importantly, it is an antigen targeted by chimeric antigen receptor (CAR) T-cells, which have already shown significant clinical activities in patients with RRMM who have undergone at least three prior treatments, including a proteasome inhibitor and an immunomodulatory agent.,Moreover, the first anti-BCMA antibody-drug conjugate also has achieved significant clinical responses in patients who failed at least three prior lines of therapy, including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory agent.,Both BCMA targeting immunotherapies were granted breakthrough status for patients with RRMM by FDA in Nov 2017.,Other promising BCMA-based immunotherapeutic macromolecules including bispecific T-cell engagers, bispecific molecules, bispecific or trispecific antibodies, as well as improved forms of next generation CAR T cells, also demonstrate high anti-MM activity in preclinical and even early clinical studies.,Here, we focus on the biology of this promising MM target antigen and then highlight preclinical and clinical data of current BCMA-targeted immunotherapies with various mechanisms of action.,These crucial studies will enhance selective anti-MM response, transform the treatment paradigm, and extend disease-free survival in MM.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Preoperative left ventricular dysfunction is a risk factor for postoperative mortality and morbidity in cardiovascular surgeries with cardiopulmonary bypass, including thoracic aortic surgery.,Using a retrospective study design, this study aimed to clarify the short- and mid-term outcomes of patients who underwent acute type A aortic dissection (ATAAD) repair with reduced left ventricular function.,Between July 2007 and February 2018, a total of 510 adult patients underwent surgical repair of ATAAD in a single institution.,The patients were classified as having left ventricular ejection fraction (LVEF) <50% (low EF group, n = 86, 16.9%) and LVEF ≥50% (normal group, n = 424, 83.1%) according to transesophageal echocardiographic assessment at the operating room.,Preoperative demographics, surgical information, and postoperative complication were compared between the two groups.,Three-year survival was analyzed using the Kaplan-Meier actuarial method.,Serial echocardiographic evaluations were performed at 1, 2, and 3 years postoperation.,Demographics, comorbidities, and surgical procedures were generally homogenous between the 2 groups, except for a lower rate of aortic arch replacement in the low EF group.,The averaged LVEFs were 44.3 ± 2.5% and 65.8 ± 6.6% among the low EF and normal groups, respectively.,The patients with low EF had higher in-hospital mortality (23.3% versus 13.9%, P = .025) compared with the normal group.,Multivariate analysis revealed that intraoperative myocardial failure requiring extracorporeal membrane oxygenation support was an in-hospital mortality predictor (odds ratio, 16.99; 95% confidence interval, 1.23-234.32; P = .034), as was preoperative serum creatinine >1.5 mg/dL.,For patients who survived to discharge, the 3-year cumulative survival rates were 77.8% and 82.1% in the low EF and normal groups, respectively (P = .522).,The serial echocardiograms revealed no postoperative deterioration of LVEF during the 3-year follow-up.,Even with a more conservative aortic repair procedure, the patients with preoperative left ventricular dysfunction are at higher surgical risk for in-hospital mortality.,However, once such patients are able to survive to discharge, the midterm outcome can still be promising.

Repair of acute type A aortic dissection (ATAAD) is a complex and emergent cardiovascular surgery that is associated with high perioperative morbidity and mortality.,Each cannulation strategy has different benefits and drawbacks during cardiopulmonary bypass.,Using a retrospective study design, we aimed to clarify the safety and efficacy of right axillary artery cannulation in combination with femoral artery cannulation compared to single arterial cannulation for ATAAD repair.,From January 2007 to July 2017, 476 adult patients underwent ATAAD repair at a single institution.,Patients were classified into groups according to their cannulation strategy: the double arterial cannulation (DAC) group (n = 377; 79.2%) or single arterial cannulation (SAC) group (n = 99; 20.8%).,Preoperative demographics, surgical information, and postoperative recovery were compared between both groups.,Survival and freedom from reoperation rates were analyzed using the Kaplan-Meier actuarial method.,Demographics, comorbidities, and surgical procedures were generally homogenous between the two groups, except for sex, age, and rate of extensive aortic repair.,Patients who underwent DAC had lower in-hospital mortality (13.5% vs.,25.3%; P = 0.005) and lower incidence of malperfusion-related complications (18.8% vs.,30.3%; P = 0.011) than those who underwent SAC.,During multivariate analysis, SAC was identified as an in-hospital mortality predictor (odds ratio, 2.81; 95% confidence interval, 1.52-5.17; P = 0.001), as were preoperative ventilator support, intraoperative extracorporeal membrane oxygenation installation, and postoperative malperfusion-related complications.,Three-year cumulative survival and freedom from reoperation rates were 74.8% and 85.3% for the DAC group and 62.6% and 81.1% for the SAC group, respectively (P = 0.010 and 0.430, respectively).,With acceptable short- and mid-term outcomes, DAC is effective and safe for establishing cardiopulmonary bypass during ATAAD repair.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide.,Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed.,This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy.,We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020.,Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ.,The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016).,For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin.,This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region.,In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

Spain has been one of the countries heavily stricken by COVID-19.,But this epidemic has not affected all regions equally.,We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain.,Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network.,We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality.,In the study period, 2737 patients were admitted with ischemic stroke.,There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001).,In-hospital mortality of stroke patients increased significantly (9.9% vs.,6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs.,16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504).,We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain.,There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.

The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.,We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).,Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers.,The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.,The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively.,The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers.,High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p < 0.0001).,There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations.,SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.,The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes.,Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients.,To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease.,Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020).,The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST).,Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years.,Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000).,The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%.,After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19.,COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke.,The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Previous studies suggested a possible gut microbiota dysbiosis in chronic heart failure (CHF).,However, direct evidence was lacking.,In this study, we investigated the composition and metabolic patterns of gut microbiota in CHF patients to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF.,We enrolled 53 CHF patients and 41 controls.,Metagenomic analyses of faecal samples and metabolomic analyses of faecal and plasma samples were then performed.,We found that the composition of gut microbiota in CHF was significantly different from controls.,Faecalibacterium prausnitzii decrease and Ruminococcus gnavus increase were the essential characteristics in CHF patients’ gut microbiota.,We also observed an imbalance of gut microbes involved in the metabolism of protective metabolites such as butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients.,Metabolic features of both faecal and plasma samples from CHF patients also significantly changed.,Moreover, alterations in faecal and plasma metabolic patterns correlated with gut microbiota dysbiosis in CHF.,Taken together, we found that CHF was associated with distinct gut microbiota dysbiosis and pinpointed the specific core bacteria imbalance in CHF, along with correlations between changes in certain metabolites and gut microbes.

The gut microbiota has been linked to cardiovascular diseases.,However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined.,Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls.,The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health.,Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort.,We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis.,Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.,The gut microbiota may play a role in cardiovascular diseases.,Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

Supplemental Digital Content is available in the text.,Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality.,Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this.,We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities.,Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke.,We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year.,Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%-46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana.,Results compared with the prior year and time trend analyses were consistent.,Reperfusion treatments also appeared to decline by 31% (95% CI, 3%-51%), and specifically thrombolysis by 33% (95% CI, 4%-55%), but this finding had less precision.,Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly.,Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study.,Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.

The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services.,We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong.,We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020-March 24, 2020).,We compared the stroke onset to hospital arrival (onset-to-door) time and timings of inpatient stroke pathways with patients admitted during the same period in 2019 (pre-COVID-19: January 23, 2019-March 24, 2019).,Seventy-three patients in COVID-19 were compared with 89 patients in pre-COVID-19.,There were no significant differences in age, sex, vascular risk factors, nor stroke severity between the 2 groups (P>0.05).,The median stroke onset-to-door time was ≈1-hour longer in COVID-19 compared with pre-COVID-19 (154 versus 95 minutes, P=0.12), and the proportion of individuals with onset-to-door time within 4.5 hours was significantly lower (55% versus 72%, P=0.024).,Significantly fewer cases of transient ischemic attack presented to the hospital during COVID-19 (4% versus 16%, P=0.016), despite no increase in referrals to the transient ischemic attack clinic.,Inpatient stroke pathways and treatment time metrics nevertheless did not differ between the 2 groups (P>0.05 for all comparisons).,During the early containment phase of COVID-19, we noted a prolongation in stroke onset to hospital arrival time and a significant reduction in individuals arriving at the hospital within 4.5 hours and presenting with transient ischemic attack.,Public education about stroke should continue to be reinforced during the COVID-19 pandemic.

This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19).,There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19.,Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2.,Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects.,A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively.,For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals.,This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion.,Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T1.,One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T1 values was also identified in an additional 7 (14.6%) individuals.,Native T2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified.,Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03).,More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation.,Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis.,Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19.

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR).,Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV).,These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water).,Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment.,There is a multitude of technical approaches and potential applications.,This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Chinese people in December 2019 and has currently spread worldwide causing the COVID-19 pandemic with more than 150,000 deaths.,In order for a SARS-CoV like virus circulating in wild life for a very long time to infect the index case-patient, a number of conditions must be met, foremost among which is the encounter with humans and the presence in homo sapiens of a cellular receptor allowing the virus to bind.,Recently it was shown that the SARS-CoV-2 spike protein, binds to the human angiotensin I converting enzyme 2 (ACE2).,This molecule is a peptidase expressed at the surface of lung epithelial cells and other tissues, that regulates the renin-angiotensin-aldosterone system.,Humans are not equal with respect to the expression levels of the cellular ACE2.,Moreover, ACE2 polymorphisms were recently described in human populations.,Here we review the most recent evidence that ACE2 expression and/or polymorphism could influence both the susceptibility of people to SARS-CoV-2 infection and the outcome of the COVID-19 disease.,Further exploration of the relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.

Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events.,Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.,The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.,MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE).,Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days.,Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45.,Time-to-event curves were calculated using the Kaplan-Meier method.,A blinded independent committee adjudicated all clinical events.,In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo.,The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days.,The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398).,Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding.,(A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564)

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

The main objective of the study was to determine the prevalence of venous thromboembolism events in patients infected with severe acute respiratory syndrome coronavirus 2 requiring venovenous extracorporeal membrane oxygenation.,The secondary objective was to compare venous thromboembolism events and coagulation variables in patients requiring venovenous extracorporeal membrane oxygenation according to the pathogen.,Retrospective observational analysis at a single center.,Tertiary referral university teaching hospital.,Patients with severe acute respiratory syndrome coronavirus 2-related severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation therapy with an injected CT scan performed after extracorporeal membrane oxygenation retrieval.,None.,We included 13 severe acute respiratory syndrome coronavirus 2 patients requiring venovenous extracorporeal membrane oxygenation.,All of these patients experienced venous thromboembolism: 10 patients (76.9%) had isolated cannula-associated deep vein thrombosis, two patients (15.4%) had isolated pulmonary embolism, and one patient (7.7%) had both cannula-associated deep vein thrombosis and pulmonary embolism.,Eleven patients (84.6%) had cannula-associated deep vein thrombosis.,A jugular associated cannula-associated deep vein thrombosis was identified in seven patients (53.8%), a femoral associated cannula-associated deep vein thrombosis was identified in 10 patients (76.9%), and six patients (46.2%) had both femoral and jugular cannula-associated deep vein thrombosis.,A pulmonary embolism was found in three patients (23.1%).,No patient had central venous catheter-related deep vein thrombosis.,One patient had thrombotic occlusion of the centrifugal pump, and one had oxygenator thrombosis requiring circuit replacement.,Three patients (23.1%) had significant bleeding.,Three patients (23.1%) had laboratory-confirmed heparin-induced thrombocytopenia, and all of them developed cannula-associated deep vein thrombosis.,These three patients had femoral cannula-associated deep vein thrombosis, and two had an oxygenator or pump thrombosis.,The mean activated partial thromboplastin time ratio was higher in the severe acute respiratory syndrome coronavirus 2 group than in the influenza group and the community-acquired pneumonia group (1.91 vs 1.48 vs 1.53; p = 0.001), which was also found in regard to the percentage of patients with an activated partial thromboplastin time ratio greater than 1.8 (47.8% vs 20% vs 20.9%; p = 0.003) and the mean prothrombin ratio (86.3 vs 61.6 vs 67.1; p = 0.003).,There was no difference in baseline characteristics or venous thromboembolism events.,We report a 100% occurrence of venous thromboembolism in critically ill patients supported by venovenous extracorporeal membrane oxygenation for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome using CT scan imaging despite a high target and close monitoring of anticoagulation.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension.,We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories.,We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment.,We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension.,We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control).,The model allowed for trends over time to be non-linear and to vary by age.,The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence.,In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men.,Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America.,Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated.,Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men.,In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan.,Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania.,Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe.,Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania.,Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran.,Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations.,The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings.,WHO.

To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration.,Systematic review and meta-analysis following PRISMA guidelines.,Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019.,Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion.,Two of three reviewers screened the records independently for eligibility.,One reviewer extracted all data and the other two reviewed the data for accuracy.,Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression.,133 studies with 12 197 participants were included.,The mean reductions (reduced sodium v usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively.,Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP.,Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals.,For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels.,In trials of less than 15 days’ duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002).,Otherwise, there was no association between trial duration and SBP reduction.,The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure.,Short term studies underestimate the effect of sodium reduction on blood pressure.,PROSPERO CRD42019140812.

Estimating the risk of pre-existing comorbidities on coronavirus disease 2019 (COVID-19) mortality may promote the importance of targeting populations at risk to improve survival.,This systematic review and meta-analysis aimed to estimate the association of pre-existing comorbidities with COVID-19 mortality.,We searched MEDLINE, SCOPUS, OVID, and Cochrane Library databases, and medrxiv.org from December 1st, 2019, to July 9th, 2020.,The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing comorbidities.,We analyzed 11 comorbidities: cardiovascular diseases, hypertension, diabetes, congestive heart failure, cerebrovascular disease, chronic kidney disease, chronic liver disease, cancer, chronic obstructive pulmonary disease, asthma, and HIV/AIDS.,Two reviewers independently extracted data and assessed the risk of bias.,All analyses were performed using random-effects models and heterogeneity was quantified.,Eleven pre-existing comorbidities from 25 studies were included in the meta-analysis (n = 65, 484 patients with COVID-19; mean age; 61 years; 57% male).,Overall, the between-study heterogeneity was medium, and studies had low publication bias and high quality.,Cardiovascular disease (risk ratio (RR) 2.25, 95% CI = 1.60-3.17, number of studies (n) = 14), hypertension (1.82 [1.43 to 2.32], n = 13), diabetes (1.48 [1.02 to 2.15], n = 16), congestive heart failure (2.03 [1.28 to 3.21], n = 3), chronic kidney disease (3.25 [1.13 to 9.28)], n = 9) and cancer (1.47 [1.01 to 2.14), n = 10) were associated with a significantly greater risk of mortality from COVID-19.,Patients with COVID-19 with cardiovascular disease, hypertension, diabetes, congestive heart failure, chronic kidney disease and cancer have a greater risk of mortality compared to patients with COVID-19 without these comorbidities.,Tailored infection prevention and treatment strategies targeting this high-risk population might improve survival.

Supplemental Digital Content is available in the text.,High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality.,While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension.,We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP.,A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm Hg for neutrophil counts; all P<10-50).,Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings.,These inverse-variance weighted estimates were consistent with other robust MR methods.,The exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses.,MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils.,Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio.,Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP.

Mitochondrial creatine kinase (Mt-CK) is a major determinant of cardiac energetic status and is down-regulated in chronic heart failure, which may contribute to disease progression.,We hypothesised that cardiomyocyte-specific overexpression of Mt-CK would mitigate against these changes and thereby preserve cardiac function.,Male Mt-CK overexpressing mice (OE) and WT littermates were subjected to transverse aortic constriction (TAC) or sham surgery and assessed by echocardiography at 0, 3 and 6 weeks alongside a final LV haemodynamic assessment.,Regardless of genotype, TAC mice developed progressive LV hypertrophy, dilatation and contractile dysfunction commensurate with pressure overload-induced chronic heart failure.,There was a trend for improved survival in OE-TAC mice (90% vs 73%, P = 0.08), however, OE-TAC mice exhibited greater LV dilatation compared to WT and no functional parameters were significantly different under baseline conditions or during dobutamine stress test.,CK activity was 37% higher in OE-sham versus WT-sham hearts and reduced in both TAC groups, but was maintained above normal values in the OE-TAC hearts.,A separate cohort of mice received in vivo cardiac 31P-MRS to measure high-energy phosphates.,There was no difference in the ratio of phosphocreatine-to-ATP in the sham mice, however, PCr/ATP was reduced in WT-TAC but preserved in OE-TAC (1.04 ± 0.10 vs 2.04 ± 0.22; P = 0.007).,In conclusion, overexpression of Mt-CK activity prevented the changes in cardiac energetics that are considered hallmarks of a failing heart.,This had a positive effect on early survival but was not associated with improved LV remodelling or function during the development of chronic heart failure.,The online version of this article (10.1007/s00395-020-0777-3) contains supplementary material, which is available to authorized users.

Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury.,However, the precise upstream molecular mechanism of fission/mitophagy remains unclear.,Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown.,Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury.,In vivo, compared to wild-type mice, DUSP1 transgenic mice (DUSP1TG mice) demonstrated a smaller infarcted area and the improved myocardial function.,In vitro, the IR-induced DUSP1 deficiency promoted the activation of JNK which upregulated the expression of the mitochondrial fission factor (Mff).,A higher expression level of Mff was associated with elevated mitochondrial fission and mitochondrial apoptosis.,Additionally, the loss of DUSP1 also amplified the Bnip3 phosphorylated activation via JNK, leading to the activation of mitophagy.,Increased mitophagy overtly consumed mitochondrial mass resulting into the mitochondrial metabolism disorder.,However, the reintroduction of DUSP1 blunted Mff/Bnip3 activation and therefore alleviated the fatal mitochondrial fission/mitophagy by inactivating the JNK pathway, providing a survival advantage to myocardial tissue following IR stress.,The results of our study suggest that DUSP1 and its downstream JNK pathway are therapeutic targets for conferring protection against IR injury by repressing Mff-mediated mitochondrial fission and Bnip3-required mitophagy.,fx1,•IR injury induces DUSP1 downregulation.,•Loss of DUSP1 leads to an increase in JNK phosphorylation.,•JNK activates Mff and Bnip3, contributing to the fatal mitochondrial fission and mitophagy, respectively.,•Fission and mitophagy induces cell damage via trigging caspase9-related apoptosis and mitochondrial energy disorder.,IR injury induces DUSP1 downregulation.,Loss of DUSP1 leads to an increase in JNK phosphorylation.,JNK activates Mff and Bnip3, contributing to the fatal mitochondrial fission and mitophagy, respectively.,Fission and mitophagy induces cell damage via trigging caspase9-related apoptosis and mitochondrial energy disorder.

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease.,The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood.,This theory is known as developmental origins of health and disease (DOHaD).,Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming.,In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins.,To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

Cardiovascular disease (CVD) presents a global health burden, despite recent advances in management.,CVD can originate from early life by so-called “developmental origins of health and disease” (DOHaD).,Epidemiological and experimental evidence supports that early-life insults can induce programming of later CVD.,Underlying the DOHaD concept, early intervention may offset programming process to prevent the development of CVD, namely reprogramming.,Oxidative stress and nutrient sensing signals have been considered to be major mechanisms of cardiovascular programming, while the interplay between these two mechanisms have not been examined in detail.,This review summarizes current evidence that supports the link between oxidative stress and nutrient sensing signaling to cardiovascular programming, with an emphasis on the l-arginine-asymmetric dimethylarginine (ADMA)-nitric oxide (NO) pathway.,This review provides an overview of evidence from human studies supporting fetal programming of CVD, insight from animal models of cardiovascular programming and oxidative stress, impact of the l-arginine-ADMA-NO pathway in cardiovascular programming, the crosstalk between l-arginine metabolism and nutrient sensing signals, and application of reprogramming interventions to prevent the programming of CVD.,A greater understanding of the mechanisms underlying cardiovascular programming is essential to developing early reprogramming interventions to combat the globally growing epidemic of CVD.

Liraglutide is an antidiabetic agent with cardioprotective effect.,The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease.,Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks.,Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR.,Intention-to-treat analysis of between-group differences was performed using ANCOVA.,Mean estimated treatment differences (95% confidence intervals) are reported.,23 patients were randomized to liraglutide and 26 to placebo.,As compared with placebo, liraglutide significantly reduced E (− 56 mL/s (− 91 to − 21)), E/A ratio (− 0.17 (− 0.27 to − 0.06)), Edec (− 0.9 mL/s2 * 10−3 (− 1.3 to − 0.2)) and E/Ea (− 1.8 (− 3.0 to − 0.6)), without affecting A (3 mL/s (− 35 to 41)) and Ea (0.4 cm/s (− 0.9 to 1.4)).,Liraglutide reduced stroke volume (− 9 mL (− 16 to − 2)) and ejection fraction (− 3% (− 6 to − 0.1)), but did not change cardiac output (− 0.4 L/min (− 0.9 to 0.2)), cardiac index (− 0.1 L/min/m2 (− 0.4 to 0.1)) and peak ejection rate (− 46 mL/s (− 95 to 3)).,Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle.,LV systolic function reduced and remained within normal range.,Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages.,Trial registration ClinicalTrials.gov: NCT01761318.

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure.,In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure.,The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated.,We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM.,This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM.,A total of 38 patients with T2DM were consecutively recruited for this study.,Left ventricular diastolic function was assessed by echocardiography.,The primary study outcome was a change in the septal E/e′ as a parameter of left ventricular diastolic function.,A total of 37 patients (25 males and 12 females) were included in the analysis.,Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%.,Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease.,Canagliflozin significantly improved left ventricular diastolic function (septal E/e′ ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001).,Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e′ ratio (p = 0.002).,In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e′ ratio.,This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM.,The benefit was especially apparent in patients with substantially improved hemoglobin values.,Trial registration UMIN Clinical Trials Registry UMIN000028141,The online version of this article (10.1186/s12933-018-0717-9) contains supplementary material, which is available to authorized users.

COVID-19 raises D-dimer (DD) levels even in the absence of pulmonary embolism (PE), resulting in an increase in computed tomography pulmonary angiogram (CTPA) requests.,Our purpose is to determine whether there are differences between DD values in PE-positive and PE-negative COVID-19 patients and, if so, to establish a new cutoff value which accurately determines when a CTPA is needed.,This study retrospectively analyzed all COVID-19 patients who underwent a CTPA due to suspected PE between March 1 and April 30, 2020, at Ramón y Cajal University Hospital, Madrid (Spain).,DD level comparisons between PE-positive and PE-negative groups were made using Student’s t test.,The optimal DD cutoff value to predict PE risk in COVID-19 patients was calculated in the ROC curve.,Two hundred forty-two patients were included in the study.,One hundred fifty-one (62%) were men and the median age was 68 years (IQR 55-78).,An increase of DD (median 3260; IQR 1203-9625 ng/mL) was detected in 205/242 (96%) patients. 73/242 (30%) of the patients were diagnosed with PE on CTPA.,The DD median value was significantly higher (p < .001) in the PE-positive group (7872, IQR 3150-22,494 ng/mL) compared with the PE-negative group (2009, IQR 5675-15,705 ng/mL).,The optimal cutoff value for DD to predict PE was 2903 ng/mL (AUC was 0.76 [CI 95% 0.69-0.83], sensitivity 81%).,The overall mortality rate was 16% (39/242).,A higher threshold (2903 ng/mL) for D-dimer could predict the risk of PE in COVID-19 patients with a sensitivity of 81%.

Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection.,The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism.,We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak.,We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization.,The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE.,PE incidence was 6.4% (29/452 patients).,Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29).,D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03).,In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-12.16), p = 0.03).,We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60).,Predictive value of AUC for ROC is 75.5%.,We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis.,An increase in D-dimer levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl.

Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.,We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States.,The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.,Clinicians abstracted the data onto standardized forms.,We report on 186 patients with MIS-C in 26 states.,The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.,Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).,The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died.,Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease-like features were documented in 74 (40%).,Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation.,The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).,Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.,(Funded by the Centers for Disease Control and Prevention.)

The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None.

The novel 2019 coronavirus disease (COVID-19), resulting from severe acute respiratory syndrome coronarvirus-2 (SARS-CoV-2) infection, typically leads to respiratory failure in severe cases; however, cardiovascular injury is reported to contribute to a substantial proportion of COVID-19 deaths.,Preexisting cardiovascular disease (CVD) is among the most common risk factors for hospitalization and death in COVID-19 patients, and the pathogenic mechanisms of COVID-19 disease progression itself may promote the development of cardiovascular injury, increasing risk of in-hospital death.,Sex differences in COVID-19 are becoming more apparent as mounting data indicate that males seem to be disproportionately at risk of severe COVID-19 outcome due to preexisting CVD and COVID-19-related cardiovascular injury.,In this review, we will provide a basic science perspective on current clinical observations in this rapidly evolving field and discuss the interplay sex differences, preexisting CVD and COVID-19-related cardiac injury.,Unlabelled Image,•Cardiovascular complications are prominent in COVID-19.,•Preexisting cardiovascular disease is a risk factor for COVID-19 severity.,•Cardiovascular disease, smoking and obesity burden more male COVID-19 patients•Cardiac injury and systemic inflammation are pronounced in male COVID-19 patients.,•No sex disparities were observed in arrhythmia and thrombosis in COVID-19 patients.,Cardiovascular complications are prominent in COVID-19.,Preexisting cardiovascular disease is a risk factor for COVID-19 severity.,Cardiovascular disease, smoking and obesity burden more male COVID-19 patients,Cardiac injury and systemic inflammation are pronounced in male COVID-19 patients.,No sex disparities were observed in arrhythmia and thrombosis in COVID-19 patients.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease.,This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke.,We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage.,Data from a total of 1463 hospitals in Germany were included.,We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019.,We identified a strong decline for hospitalization of AIS (−17.4%), transient ischemic attack (−22.9%), and intracerebral hemorrhage (−15.8%) patients during the pandemic compared with prepandemic period.,IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044).,In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006).,Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany.

Supplemental Digital Content is available in the text.,Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke.,Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways.,We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries.,To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019.,Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site).,The median National Institute of Health Stroke Scale was 10 (interquartile range [IQR], 4-18).,In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institute of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institute of Health Stroke Scale score).,There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke.,Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge.,In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19.,Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis.,However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data.,This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19.,We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization.,Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization.,A total of 305 patients were included.,Mean age was 63 years and 205 patients (67.2%) were male.,Overall, myocardial injury was observed in 190 patients (62.3%).,Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions.,Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.,Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities.,Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury.,Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown.,To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data.,A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020.,These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis.,The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve.,Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis.,The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively.,PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography.,DVT was present in 42.4% of patients with PE.,D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively).,Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT.,The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19.,© RSNA, 2020,Supplemental material is available for this article.,See also the editorial by Woodard in this issue.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.