Circulation

The widespread use of cardiac implantable electronic devices and wearable monitors has led to the detection of subclinical atrial fibrillation in a substantial proportion of patients. There is evidence that these asymptomatic arrhythmias are associated with increased risk of stroke. Thus, detection of subclinical atrial fibrillation may offer an opportunity to reduce stroke risk by initiating anticoagulation. However, it is unknown whether long-term anticoagulation is warranted and in what populations. This scientific statement explores the existing data on the prevalence, clinical significance, and management of subclinical atrial fibrillation and identifies current gaps in knowledge and areas of controversy and consensus...

Background: Prosthetic valve endocarditis (PVE) is a rare but critical mechanism of valve failure and death after transcatheter and surgical aortic valve replacement (TAVR, SAVR) warranting further analysis in modern AVR experience. We characterize the incidence, risk factors, microbiological profile and outcomes of PVE from the PARTNER trials and registries. Methods: We analyzed a pooled cohort of all patients in PARTNER-I and PARTNER-II trials and registries. Patients had severe aortic stenosis, were treated with TAVR or SAVR, and were analyzed with respect to development of PVE...

Background: The maternal circulatory system and hormone balance both change dynamically during pregnancy, delivery, and the postpartum period. Although atrial and brain natriuretic peptides (ANP and BNP, respectively) produced in the heart control circulatory homeostasis through their common receptor, NPR1, the physiological and pathophysiological roles of endogenous ANP/BNP in the perinatal period are not fully understood. Methods: To clarify the physiological and pathophysiological roles of the endogenous ANP/BNP-NPR1 system during the perinatal period, the phenotype of female wild-type and conventional or tissue-specific Npr1-knockout mice during the perinatal period was examined, especially focusing on maternal heart weight, blood pressure, and cardiac function...

Background: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure (HF). Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. Methods: Here we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine non-ischemic, pressure-overload HF model. By focusing our analysis on CD45+ cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls...

Background: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence following atrial fibrillation (AF) ablation. Methods: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contactforce guided RF ablation (CF-RF ablation, 115), 4-minute cryoballoon ablation (CRYO-4, 115), or 2-minute cryoballoon ablation (CRYO-2, 116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 post ablation, or a repeat ablation procedure at any time...

No abstract text is available yet for this article.

Members of the white race have consistently exhibited a higher prevalence and incidence of atrial fibrillation (AF).1 This observation has been referred to as the racial paradox, given that minorities often experience more traditional AF risk factors than whites.2 Although American Indians exhibit high rates of AF risk factors, they have not been included in previous research that has examined the relationship between race and incident AF. We used the Healthcare Cost and Utilization Project (HCUP) California State Databases to identify California residents ({greater than or equal to}18 years of age) who received care in an emergency department, inpatient hospital unit, or ambulatory surgery setting between January 1, 2005, and December 31, 2011...

No abstract text is available yet for this article.

Background: Numerous scales exist for classification of major bleeding events. There are limited data comparing the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation (AF). Here we analyze bleeding outcomes according to the ISTH, TIMI, GUSTO, and BARC bleeding scales in the ENGAGE AF (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation)-TIMI 48 trial of edoxaban vs warfarin. Methods: 21,105 patients with AF at risk for stroke (CHADS2 ≥2) were enrolled in the ENGAGE AF-TIMI 48 trial (NCT00781391) comparing warfarin to a higher (HDER; 60/30 mg daily) or lower (LDER; 30/15 mg daily) dose edoxaban regimen...

Background: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory IgG receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension. Methods: Involvement of IgG was studied using IgG μ heavy chain-null mice deficient in mature B cells, and by IgG transfer...

Background: The giant sarcomere protein titin is important in both heart health and disease. Mutations in the gene encoding for titin, TTN , are the leading known cause of familial dilated cardiomyopathy. The uneven distribution of these mutations within TTN motivated us to seek a more complete understanding of this gene and the isoforms it encodes in cardiomyocyte sarcomere formation and function. Methods: To investigate the function of titin in human cardiomyocytes (CMs), we used CRISPR/Cas9 to generate homozygous truncations in the Z-disk (TTN-Z-/- ) and A-band (TTN-A-/- ) regions of the TTN gene in human induced pluripotent stem cells...

Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin (hs-cTn) testing and classification of patients with myocardial injury based on aetiology, but the clinical implications of implementing this guideline are not well understood. Methods: In a stepped-wedge cluster randomized controlled trial, we implemented a hs-cTn assay and the recommendations of the Universal Definition in 48,282 consecutive patients with suspected acute coronary syndrome...

Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings...

Background: Cardiac kinases play a critical role in the development of heart failure, and represent potential tractable therapeutic targets. However, only a very small fraction of the cardiac kinome has been investigated. To identify novel cardiac kinases involved in heart failure, we employed an integrated transcriptomics and bioinformatics analysis and identified Homeodomain-Interacting Protein Kinase 2 (HIPK2) as a novel candidate kinase. The role of HIPK2 in cardiac biology is unknown. Methods: We used the Expression2Kinase algorithm for the screening of kinase targets...

Background: Heart failure is a complex syndrome that results from structural or functional impairment of ventricular filling or blood ejection. Protein phosphorylation is a major and essential intracellular mechanism that mediates various cellular processes in cardiomyocytes in response to extracellular and intracellular signals. The RHOA-associated protein kinase (ROCK/Rho-kinase), an effector regulated by the small GTPase RHOA, causes pathological phosphorylation of proteins, resulting in cardiovascular diseases...

Background: Studies of patients with cardiovascular implantable electronic devices (CIED) show a relationship between atrial fibrillation (AF) duration and stroke risk, though the interaction with CHA2 DS2 -VASc score is poorly defined. The objective of this study is to evaluate rates of stroke and systemic embolism (SSE) in CIED patients as a function of both CHA2 DS2 -VASc score and AF duration. Methods: Data from the Optum© electronic health record (EHR) de-identified database (2007-2017) were linked to the Medtronic CareLinkTM database of CIEDs capable of continuous AF monitoring...

No abstract text is available yet for this article.

Background: The COAPT trial demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) using the MitraClip resulted in reduced mortality and heart-failure hospitalizations and improved quality of life when compared with maximally-tolerated guideline-directed medical therapy (GDMT) in heart-failure patients with 3-4+ secondary mitral regurgitation (SMR). Whether TMVr is cost-effective compared with GDMT in this population is unknown. Methods: We used data from the COAPT trial to perform a formal, patient-level economic analysis of TMVr + GDMT vs...

Optimal antithrombotic therapy after percutaneous coronary interventions in high bleeding risk (HBR) patients is an important issue under active discussion. However, no previous study has compared different dual antiplatelet therapy (DAPT) duration in HBR patients. Recently, we have reported the STOPDAPT-2 (Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent) trial, suggesting the benefit of 1-month DAPT over 12-month DAPT with reduction of bleeding events without increase in cardiovascular events in an all-comer population1 ...

Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation (AF) who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. Methods: Using a 2×2 factorial design we compared apixaban with vitamin K antagonists (VKA) and aspirin with placebo in patients with AF who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in three pre-specified subgroups: patients with ACS treated medically, ACS treated with PCI, and those undergoing elective PCI...