The 50 most-cited articles in Circulation, 2020

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2020 Statistical Update…

mitral stenosis ◼ mitral transcatheter edge-to-edge repair ◼ prosthetic valve ◼ pulmonic regurgitation ◼ pulmonic stenosis ◼ transcatheter aortic valve replacement or implantation ◼ tricuspid regurgitation ◼ tricuspid stenosis ◼ valvular heart disease

AIM: This executive summary of the valvular heart disease guideline provides recommendations for clinicians to diagnose and manage valvular heart disease as well as supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from January 1, 2010, to March 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected database relevant to this guideline. STRUCTURE: Many recommendations from the earlier valvular heart disease guidelines have been updated with new evidence and provides newer options for diagnosis and treatment of valvular heart disease. This summary includes only the recommendations from the full guideline which focus on diagnostic work-up, the timing and choice of surgical and catheter interventions, and recommendations for medical therapy. The reader is referred to the full guideline for graphical flow charts, text, and tables with additional details about the…

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during…

BACKGROUND: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. METHODS: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. RESULTS: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection…

resuscitation ◼ defibrillators ◼ delivery of health care ◼ echocardiography ◼ electric countershock ◼ epinephrine ◼ extracorporeal membrane oxygenation ◼ heart arrest ◼ infusions, intraosseous ◼ intubation, intratracheal

◼ pulmonary embolism ◼ thrombosis ◼ von Willebrand factor W e report a case series of patients with coronavirus disease 2019 (CO-VID-19) with pulmonary embolism (PE) in our institution.Lille University Hospital is the tertiary care center for the North of France, the second greatest French region in population density (189 people per 1 km 2 ), also considered a metabolic area with high number of overweight patients.The study was approved by the institutional data protection authority of Lille University Hospital.Among the 107 first consecutive patients with confirmed COVID-19 admitted to the intensive care unit (ICU) for pneumonia from February 27 to March 31, we noticed an unexpectedly high number of PEs during their stay in the ICU: 22 (20.6%) at the time of analysis (April 9), within a median time from ICU admission of 6 days (range, 1-18 days).To determine whether this represents an increase in the expected incidence of PE over a similar time interval, we analyzed the files of 196 patients hospitalized in our ICU during the same time interval in 2019.Despite a similar severity…

Structural racism has been and remains a fundamental cause of persistent health disparities in the United States. The coronavirus disease 2019 (COVID-19) pandemic and the police killings of George Floyd, Breonna Taylor, and multiple others have been reminders that structural racism persists and restricts the opportunities for long, healthy lives of Black Americans and other historically disenfranchised groups. The American Heart Association has previously published statements addressing cardiovascular and cerebrovascular risk and disparities among racial and ethnic groups in the United States, but these statements have not adequately recognized structural racism as a fundamental cause of poor health and disparities in cardiovascular disease. This presidential advisory reviews the historical context, current state, and potential solutions to address structural racism in our country. Several principles emerge from our review: racism persists; racism is experienced; and the task of dismantling racism must belong to all of society. It cannot be accomplished by affected individuals…

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially…

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment…

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction. Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses. Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0–5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score ( r =0.34; P <0.001), strongly with coronary artery calcium score ( r =0.62; P <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r…

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices,…

BACKGROUND: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. METHODS: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. RESULTS: We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and…

Cardiorespiratory fitness (CRF) refers to the capacity of the circulatory and respiratory systems to supply oxygen to skeletal muscle mitochondria for energy production needed during physical activity. CRF is an important marker of physical and mental health and academic achievement in youth. However, only 40% of US youth are currently believed to have healthy CRF. In this statement, we review the physiological principles that determine CRF, the tools that are available to assess CRF, the modifiable and nonmodifiable factors influencing CRF, the association of CRF with markers of health in otherwise healthy youth, and the temporal trends in CRF both in the United States and internationally. Development of a cost-effective CRF measurement process that could readily be incorporated into office visits and in field settings to screen all youth periodically could help identify those at increased risk.

BACKGROUND: 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. METHODS: 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. RESULTS: 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…

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality. A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease. The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy. Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis. Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury. Prior experience with severe acute respiratory syndrome coronavirus 1 has helped…

BACKGROUND: Immune checkpoint inhibitors (ICIs) treat an expanding range of cancers. Consistent basic data suggest that these same checkpoints are critical negative regulators of atherosclerosis. Therefore, our objectives were to test whether ICIs were associated with accelerated atherosclerosis and a higher risk of atherosclerosis-related cardiovascular events. METHODS: The study was situated in a single academic medical center. The primary analysis evaluated whether exposure to an ICI was associated with atherosclerotic cardiovascular events in 2842 patients and 2842 controls matched by age, a history of cardiovascular events, and cancer type. In a second design, a case-crossover analysis was performed with an at-risk period defined as the 2-year period after and the control period as the 2-year period before treatment. The primary outcome was a composite of atherosclerotic cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke). Secondary outcomes included the individual components of the primary outcome. In addition, in an imaging substudy…

BACKGROUND: Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19. METHODS: A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls). We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well. RESULTS: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. Patients with COVID-19 also present with…

Background: Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD. Methods: We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in…

BACKGROUND: The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low-input RNA sequencing have allowed definitions of cellular transcriptomes at single-cell resolution at scale, we have applied these approaches to assess the cellular and transcriptional diversity of the nonfailing human heart. METHODS: Microfluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from 7 human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based on transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic data. RESULTS: We sequenced the transcriptomes of 287 269 single cardiac nuclei, revealing 9 major cell types and 20…

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Uriel and Sayer), who respond to the information and share their reasoning with the reader (regular type

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes mellitus, hypertension, and other modifiable lifestyle-related factors. Fortunately, many of these AF drivers are potentially reversible, and emerging evidence supports that addressing these modifiable risks may be effective for primary and secondary AF prevention. A structured, protocol-driven multidisciplinary approach to integrate lifestyle and risk factor management as an integral part of AF management may help in the prevention and treatment of AF. However, this aspect of AF management is currently underrecognized, underused, and understudied. The purpose of this American Heart Association scientific statement is to review the association of modifiable risk factors with AF and the…

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences…

Background: Mutations in desmoplakin ( DSP ), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy. Clinical correlates of DSP cardiomyopathy have been limited to small case series. Methods: Clinical and genetic data were collected on 107 patients with pathogenic DSP mutations and 81 patients with pathogenic plakophilin 2 ( PKP2 ) mutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed. Results: DSP and PKP2 cohorts included similar proportions of probands (41% versus 42%) and patients with truncating mutations (98% versus 100%). Left ventricular (LV) predominant cardiomyopathy was exclusively present among patients with DSP (55% versus 0% for PKP2 , P <0.001), whereas right ventricular cardiomyopathy was present in only 14% of patients with DSP versus 40% for PKP2 ( P <0.001). Arrhythmogenic right ventricular cardiomyopathy diagnostic criteria had poor sensitivity for DSP…

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for…

Cardio-obstetrics has emerged as an important multidisciplinary field that requires a team approach to the management of cardiovascular disease during pregnancy. Cardiac conditions during pregnancy include hypertensive disorders, hypercholesterolemia, myocardial infarction, cardiomyopathies, arrhythmias, valvular disease, thromboembolic disease, aortic disease, and cerebrovascular diseases. Cardiovascular disease is the primary cause of pregnancy-related mortality in the United States. Advancing maternal age and preexisting comorbid conditions have contributed to the increased rates of maternal mortality. Preconception counseling by the multidisciplinary cardio-obstetrics team is essential for women with preexistent cardiac conditions or history of preeclampsia. Early involvement of the cardio-obstetrics team is critical to prevent maternal morbidity and mortality during the length of the pregnancy and 1 year postpartum. A general understanding of cardiovascular disease during pregnancy should be a core knowledge area for all cardiovascular and primary care clinicians. This…

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and…

BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional…

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular…

Background: To investigate deep vein thrombosis (DVT) in hospitalized patients with coronavirus disease 2019 (COVID-19), we performed a single institutional study to evaluate its prevalence, risk factors, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center. Methods: We studied a total of 143 patients with COVID-19 from January 29, 2020 to February 29, 2020. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities, and outcome variables were obtained, and comparisons were made between groups with and without DVT. Results: Of the 143 patients hospitalized with COVID-19 (age 63±14 years, 74 [51.7%] men), 66 patients developed lower extremity DVT (46.1%: 23 [34.8%] with proximal DVT and 43 [65.2%] with distal DVT). Compared with patients who did not have DVT, patients with DVT were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis, including an increased proportion of deaths (23 [34.8%] versus 9 [11.7%]; P =0.001) and a decreased proportion of patients…

Heart failure with preserved ejection fraction (HFpEF), a major public health problem that is rising in prevalence, is associated with high morbidity and mortality and is considered to be the greatest unmet need in cardiovascular medicine today because of a general lack of effective treatments. To address this challenging syndrome, the National Heart, Lung, and Blood Institute convened a working group made up of experts in HFpEF and novel research methodologies to discuss research gaps and to prioritize research directions over the next decade. Here, we summarize the discussion of the working group, followed by key recommendations for future research priorities. There was uniform recognition that HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach in both humans and animal models to improve understanding of mechanisms and treatment of HFpEF. It was recognized that advances in the understanding of basic mechanisms and the roles of inflammation, macrovascular and microvascular dysfunction, fibrosis, and tissue remodeling are…

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II to IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 versus 519 patients; empagliflozin versus placebo, respectively; hazard ratio [HR], 0.76; 95% CI, 0.67–0.87; P <0.0001). This benefit reached…

oronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is causing a dramatic pandemic. 1ombardy, in northern Italy, is one of the most affected regions worldwide. 2ardiovascular complications occur frequently in patients with COVID-19, 3 with challenges in acute management.We aimed to evaluate incidence, clinical presentation, angiographic findings, and clinical outcomes of ST-elevation myocardial infarction (STEMI) in patients with COVID-19.All hospitals with catherization laboratories in Lombardy were contacted to collect cases of patients with confirmed COVID-19 who underwent an urgent coronary angiogram because of STEMI between February 20, 2020 (date of first COVID-19 case in Lombardy) and March 30, 2020. 2 Data were collected retrospectively, in anonymized fashion without any sensitive data, therefore not requiring institutional review board approval.COVID-19 was confirmed with reverse transcription-polymerase chain reaction assays.STEMI was defined based on the presence of typical symptoms associated with ST-segment…

xisting American Heart Association cardiopulmonary resuscitation (CPR) guidelines do not address the challenges of providing resuscitation in the setting of the coronavirus disease 2019 (COVID-19) global pandemic, wherein rescuers must continuously balance the immediate needs of the patients with their own safety.To address this gap, the American Heart Association, in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists, and with the support of the American Association of Critical Care Nurses and National Association of EMS Physicians, has compiled interim guidance to help rescuers treat individuals with cardiac arrest with suspected or confirmed COVID-19.Over the past 2 decades, there has been a steady improvement in survival after cardiac arrest occurring both inside and outside the hospital. 1That success has relied on initiating proven resuscitation interventions such as high-quality chest compressions…

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: =0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in…

BACKGROUND: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites. METHODS: ). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined. RESULTS: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus,…

Epidemiological and biological plausibility studies support a cause-and-effect relationship between increased levels of physical activity or cardiorespiratory fitness and reduced coronary heart disease events. These data, plus the well-documented anti-aging effects of exercise, have likely contributed to the escalating numbers of adults who have embraced the notion that "more exercise is better." As a result, worldwide participation in endurance training, competitive long distance endurance events, and high-intensity interval training has increased markedly since the previous American Heart Association statement on exercise risk. On the other hand, vigorous physical activity, particularly when performed by unfit individuals, can acutely increase the risk of sudden cardiac death and acute myocardial infarction in susceptible people. Recent studies have also shown that large exercise volumes and vigorous intensities are both associated with potential cardiac maladaptations, including accelerated coronary artery calcification, exercise-induced cardiac biomarker release, myocardial…

Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced…

Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target…

Background: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18–85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven…

Background: Cardiovascular disease is the leading cause of death among women worldwide, yet, women have historically been underrepresented in cardiovascular trials. Methods: We systematically assessed the participation of women in completed cardiovascular trials registered in ClinicalTrials.gov between 2010 and 2017, and extracted publicly available information including disease type, sponsor type, country, trial size, intervention type, and the demographic characteristics of trial participants. We calculated the female-to-male ratio for each trial and determined the prevalence-adjusted estimates for participation of women by dividing the percentage of women among trial participants by the percentage of women in the disease population (participation prevalence ratio; a ratio of 0.8 to 1.2 suggests comparable prevalence and good representation). Results: We identified 740 completed cardiovascular trials including a total of 862 652 adults, of whom 38.2% were women. The median female-to-male ratio of each trial was 0.51 (25th quartile, 0.32; 75th quartile, 0.90) overall and varied by…

Background: Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required. Methods: Utilizing an evidence-based framework, 3 gene curation teams blinded to each other’s work scored the level of evidence for 17 genes reported to cause LQTS. A Clinical Domain Channelopathy Working Group provided a final classification of these genes for causation of LQTS after assessment of the evidence scored by the independent curation teams. Results: Of 17 genes reported as being causative for LQTS, 9 ( AKAP9, ANK2, CAV3, KCNE1, KCNE2, KCNJ2, KCNJ5, SCN4B, SNTA1 ) were classified as having limited or disputed evidence as LQTS-causative genes. Only 3 genes ( KCNQ1, KCNH2, SCN5A ) were curated as definitive genes for typical LQTS. Another 4 genes ( CALM1, CALM2, CALM3, TRDN ) were found to have strong or definitive evidence…

Newborn resuscitation requires anticipation and preparation by providerswho train individually and as teams.2. Most newly born infants do not require immediate cord clamping or resuscitation and can be evaluated and monitored during skin-to-skin contact with their mothers after birth.3. Inflation and ventilation of the lungs are the priority in newly born infants who need support after birth.4. A rise in heart rate is the most important indicator of effective ventilation and response to resuscitative interventions. 5. Pulse oximetry is used to guide oxygen therapy and meet oxygen saturation goals.6. Chest compressions are provided if there is a poor heart rate response to ventilation after appropriate ventilation corrective steps, which preferably include endotracheal intubation.7. The heart rate response to chest compressions and medications should be monitored electrocardiographically. 8.If the response to chest compressions is poor, it may be reasonable to provide epinephrine, preferably via the intravenous route.9. Failure to respond to epinephrine in a newborn with history or…

Understanding and addressing the unique health needs of people residing in rural America is critical to the American Heart Association's pursuit of a world with longer, healthier lives. Improving the health of rural populations is consistent with the American Heart Association's commitment to health equity and its focus on social determinants of health to reduce and ideally to eliminate health disparities. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders to make rural populations a priority in programming, research, and policy. This advisory first summarizes existing data on rural populations, communities, and health outcomes; explores 3 major groups of factors underlying urban-rural disparities in health outcomes, including individual factors, social determinants of health, and health delivery system factors; and then proposes a set of solutions spanning health system innovation, policy, and research aimed at improving rural health.

The diagnosis and management of hypertension, a common cardiovascular risk factor among the general population, have been based primarily on the measurement of blood pressure (BP) in the office. BP may differ considerably when measured in the office and when measured outside of the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Self-measured BP monitoring, the measurement of BP by an individual outside of the office at home, is a validated approach for out-of-office BP measurement. Several national and international hypertension guidelines endorse self-measured BP monitoring. Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension. Validated self-measured BP monitoring devices that use the oscillometric method are preferred, and a standardized BP measurement and monitoring protocol should be…