Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.

Impedance is the ratio of voltage to current in an electrical circuit. Cardiovascular implantable electronic devices measure impedance to assess the structural integrity electrical performance of leads, typically using subthreshold pulses. We review determinants of impedance, how it is measured, variation in clinically measured pacing and high-voltage impedance and impedance trends as a diagnostic for lead failure and lead-device connection problems. We consider the differential diagnosis of abnormal impedance and the approach to the challenging problem of a single, abnormal impedance measurement. Present impedance provides a specific but insensitive diagnostic. For pacing circuits, we review the complementary roles of impedance and more sensitive oversensing diagnostics. Shock circuits lack a sensitive diagnostic. This deficiency is particularly important for insulation breaches, which may go undetected and present with short circuits during therapeutic shocks. We consider new methods for measuring impedance that may increase sensitivity for insulation breaches.

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.

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.

Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations.

Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 patients with DCM across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60 706 individuals to identify clinically interpretable genes robustly associated with dominant monogenic DCM.

Pulsed field ablation (PFA) can be myocardium selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA).

Adjunctive coronary atherectomy (CA) can be utilized in treating severely calcified coronary lesions; however, the temporal trends, patient selection, and variation in use of CA have not been well described. We sought to assess the trends in usage, interhospital variability, and outcomes with CA among patients undergoing percutaneous coronary intervention (PCI).

The temporal occurrence of arrhythmic complications after alcohol septal ablation (ASA) is unclear. As a result, the appropriate time to monitor patients after ASA is controversial. The purpose of this study is to determine the temporal occurrence of complete heart block (CHB) and ventricular tachyarrhythmia (VT) after ASA to better understand when patients can be safely discharged.

Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies.

We conducted a pilot study to assess feasibility, on-study retention, trends in natriuretic peptide levels, quality of life, and safety of a 12-week feeding trial with 1500- versus 3000-mg daily sodium meals in high-risk patients with heart failure.

Despite advances in reperfusion times, patients presenting with acute myocardial infarction carry an unacceptably high rate of mortality and morbidity. Mechanical unloading of the left ventricle (LV) has been suggested to reduce infarct size after acute myocardial infarction. Although prior studies have investigated LV unloading during ischemia with a delay in reperfusion, little is known about the optimal timing for LV unloading in the setting of acute myocardial infarction.