The strongest genetic risk factors for atrial fibrillation (AF) are DNA variants on chromosome 4q25 near the transcription factor gene PITX2 (Pitx2:Paired-like homeodomain transcription factor 2). Mice deficient in Pitx2 (Pitx2+/-) have increased AF susceptibility, although the molecular mechanism(s) remains controversial. Pitx2 encodes a transcription factor that activates an antioxidant response to promote cardiac repair. Increased reactive oxygen species causing oxidation of polyunsaturated fatty acids generates reactive lipid dicarbonyl moieties that adduct to proteins and other macromolecules to promote cellular injury. We tested the hypothesis that oxidative stress, and specifically isolevuglandins, the most reactive lipid dicarbonyls identified, are increased in the setting of Pitx2 deficiency to promote proarrhythmic remodeling and AF.

The safety of subcutaneous implantable cardioverter defibrillator (S-ICD) recipients who lead active lifestyles and engage in recreational sports is unknown. We aimed to evaluate the association between lifestyle and recreational sports and the occurrence of arrhythmia- and device-related complications, appropriate and inappropriate shocks in S-ICD recipients.

The authorization process and coverage/reimbursement mechanisms for medical devices play critical roles in device adoption and usage. However, international variation in these processes remains poorly characterized, especially with regard to data transparency and the effects of reimbursement on usage.

Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation.

Circular RNAs derived from both nuclear and mitochondrial genomes are identified in animal cells. Mitochondria-encoded circular RNAs (mecciRNAs) are attracting more attention, and several members of mecciRNAs have already been recognized in regulating mitochondrial functions. Mitochondria dysfunctions are well-known to participate in heart failure (HF). This study was designed to investigate the RNA metabolism of mecciRNAs and the relevant roles and potential application of mecciRNAs in HF.

Remote monitoring offers an effective and safe method for monitoring patients with cardiovascular implantable electronic devices. The downside of remote monitoring is the overflow of the data. Since many of the remote monitoring transmissions are nonactionable, optimizing alert transmissions could partly overcome this problem.

Sudden cardiac death is the most common cause of death in childhood hypertrophic cardiomyopathy (HCM). Recently, 2 risk scores have been developed to estimate the 5-year risk of sudden cardiac death. We aimed to assess their respective performances in an independent cohort.

Larry A. Allen, MD, MHS, FAHA, FACC; Mats Börjesson, MD, PhD, FACC; Alan C. Braverman, MD, FACC; Julie A. Brothers, MD; Silvia Castelletti, MD, MSc, FESC; Eugene H. Chung, MD, MPH, FHRS, FAHA, FACC; Timothy W. Churchill, MD, FACC; Guido Claessen, MD, PhD; Flavio D'Ascenzi, MD, PhD; Douglas Darden, MD; Peter N. Dean, MD, FACC; Neal W. Dickert, MD, PhD, FACC; Jonathan A. Drezner, MD; Katherine E. Economy, MD, MPH; Thijs M.H. Eijsvogels, PhD; Michael S. Emery, MD, MS, FACC; Susan P. Etheridge, MD, FHRS, FAHA, FACC; Sabiha Gati, BSc (Hons), MBBS, PhD, MRCP, FESC; Belinda Gray, BSc (Med), MBBS, PhD; Martin Halle, MD; Kimberly G. Harmon, MD; Jeffrey J. Hsu, MD, PhD, FAHA, FACC; Richard J. Kovacs, MD, FAHA, MACC; Sheela Krishnan, MD, FACC; Mark S. Link, MD, FHRS, FAHA, FACC; Martin Maron, MD; Silvana Molossi, MD, PhD, FACC; Antonio Pelliccia, MD; Jack C. Salerno, MD, FACC, FHRS; Ankit B. Shah, MD, MPH, FACC; Sanjay Sharma, BSc (Hons), MBChB, MRCP (UK), MD; Tamanna K. Singh, MD, FACC; Katie M. Stewart, NP, MS; Paul D. Thompson, MD, FAHA, FACC; Meagan M. Wasfy, MD, MPH, FACC; Matthias Wilhelm, MD.

Bleeding after starting anticoagulation for atrial fibrillation (AF) may be the first sign of malignancy, especially in elderly individuals. There are no recommendations to guide investigations for malignancy after new-onset bleeding after anticoagulation for AF. Our objective was to determine the association of bleeding after starting oral anticoagulation for AF with new diagnoses of malignancy in a population-wide sample.

Groundbreaking achievements in science and medicine have contributed to reductions in cardiovascular disease and stroke mortality over the past 7 decades. Many of these advances were supported through investments by the National Institutes of Health, the global leader in funding biomedical research. This public investment has produced important economic returns, including supporting >400 000 jobs and roughly $93 billion in economic activity in the United States. Unfortunately, public funding has not kept pace with the burden of disease or rates of inflation. As the nation's oldest and largest volunteer organization dedicated to fighting heart disease and stroke, research is critical to the American Heart Association's mission. Given the American Heart Association's unique position in representation of patients, clinicians, and scientists and as a research funder, we offer the following principles to optimize the future of the US biomedical research enterprise in general and the National Institutes of Health in particular. Specifically, the United States should continue to prioritize innovative and impactful research; to improve efficiency and transparency in its peer review process; to lead in translating evidence into practice; to support the current and future biomedical workforce; and to ensure robust and reliable public investment for the future. The American Heart Association reiterates our strong support for the National Institutes of Health and federal agencies that fund and implement biomedical and population-based research initiatives, which yield important economic returns. These agencies are vital to support today's current and future health challenges, to drive foundational science, to improve patient health, to reduce the global disease burden, to address upstream and preventive strategies, and to improve the value of our public health and health care investments.

Pathogenic/likely pathogenic (LP) desmin (DES) variants cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease, sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, left ventricular assist device/cardiac transplant, HF-related death) in patients with pathogenic/LP DES variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with pathogenic/LP DES variants through a systematic review and individual patient data meta-analysis using published reports.

Truncating variants (TTNtvs) in the titin (TTN) gene have been associated with cardiomyopathies or arrhythmias (C/A) and autosomal recessive neuromuscular diseases (NM). However, the clinical significance of TTNtvs across the entire coding sequence of TTN has not been comprehensively assessed. The purpose of this study was to examine the burden of TTNtvs in C/A and NM cases compared with controls in the genome aggregation database.

Periprocedural myocardial injury (PMI) with or without type 4a myocardial infarction (MI) might occur in patients with non-ST-segment-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI). This study investigated the incidence and prognostic relevance of these events, according to current definitions, in patients with NSTEMI undergoing PCI. The best cardiac troponin I (cTnI) threshold of PMI for prognostic stratification is also suggested.

Intravascular imaging-guided percutaneous coronary intervention (PCI) has been shown to improve clinical outcomes in patients with complex coronary artery lesions compared with angiography-guided PCI. However, the prognostic impact of suboptimal findings on intravascular imaging such as stent underexpansion, malapposition, or dissection is unclear in the era of contemporary drug-eluting stents.

Hypoattenuated leaflet thickening (HALT) is believed to reflect leaflet thrombosis; however, no systematic histological examination of HALT has ever been performed. The aim of this study was to evaluate histological findings of explanted self-expanding transcatheter aortic bioprosthetic valves from clinical trials and to compare microCT findings of suspected HALT with histology findings of valve thrombosis and its characterization over time.

Riociguat and balloon pulmonary angioplasty (BPA) improve hemodynamics in inoperable chronic thromboembolic pulmonary hypertension. Importantly, comparative effects of riociguat and BPA on different components of right ventricular (RV) afterload and function remain not fully elucidated.