Remote monitoring has revolutionized the follow-up of cardiac implantable electronic device recipients, leading to both organizational benefits and improved patient survival. To fully realize the potential of a remote cardiac implantable electronic device management strategy, a 2-way communication system enabling remote programming capabilities is essential. In recent years, several initiatives have emerged to develop and evaluate indirect remote programming solutions based on the remote control of a device programmer. This hybrid approach, which mitigates cybersecurity risks, has been successfully applied in various clinical settings, from magnetic resonance imaging procedures to medically underserved regions, and has consistently demonstrated high safety and patient satisfaction. Indirect remote programming reduces the need for both patient and healthcare professional travel, thereby lowering associated costs and the carbon footprint, while shortening delays and enhancing patient safety. It provides a clear preview of the enormous potential of direct remote programming, particularly regarding equity in access to care and patient outcomes. Direct remote programming of cardiac implantable electronic devices is no longer technical a barrier and is already available for implantable cardiac monitors. In the near future, extending direct programming to therapeutic cardiac implantable electronic devices is expected to further remove geographic and logistical barriers, reduce time to intervention, and improve patient safety. This promising evolution will, however, require not only addressing cybersecurity challenges but also embracing a paradigm shift within the cardiology community.

Polypharmacy in patients with cardiovascular disease occurs frequently across the age spectrum and can lead to inappropriate prescribing and adverse outcomes. Despite polypharmacy being a known problem for decades, there is limited guidance describing how to manage polypharmacy in patients with cardiovascular disease, including when and how to initiate deprescribing strategies. Although polypharmacy can occur at any age, studies often focus on older adults. The prevalence and consequences of polypharmacy, coupled with current gaps in the deprescribing literature, highlight the need for a scientific statement focused on deprescribing in all patients with cardiovascular disease. Deprescribing can improve outcomes and can apply to both cardiovascular and noncardiovascular drugs because both contribute to polypharmacy and poor outcomes associated with inappropriate prescribing in patients with cardiovascular disease. This scientific statement reviews the consequences of polypharmacy in patients with cardiovascular disease and provides tailored deprescribing strategies across the life span, with an emphasis on the unique considerations in pediatric, adult, and older adult populations. These strategies include observing clinical cues and triggers, using validated deprescribing tools, engaging in shared decision-making, and leveraging the roles of all members of the health care team to address barriers to deprescribing. Last, this scientific statement highlights current challenges related to polypharmacy and deprescribing and suggests some strategies to address them.

Titin truncating variants (TTNtv) represent the most common genotype underlying dilated cardiomyopathy but are also detected in the general population, exhibiting incomplete penetrance and marked phenotypic variability. This heterogeneity complicates clinical interpretation and risk stratification. Emerging molecular evidence suggests that truncating location within the gene may influence disease mechanisms. We aimed to investigate whether TTNtv location also affects clinical phenotype and prognosis.

A combined strategy of atherectomy followed by intravascular lithotripsy (dual-prep strategy) for severely calcified lesions may optimize stent deployment, but mechanistic evidence from prospective optical coherence tomography (OCT) imaging is limited. This study was designed to comprehensively characterize patterns of calcium modification during a dual-preparation strategy and to explore imaging determinants of calcium fracture and stent expansion using serial and 3-dimensional OCT assessment.

Inherited PLN (phospholamban) R14del variants cause dilated cardiomyopathy with a high burden of malignant ventricular arrhythmias. However, the single-cell electrophysiological substrate underlying arrhythmogenicity is incompletely characterized, and it is unclear whether antiarrhythmic agents validated in wild-type (WT) or long QT models retain efficacy in this genotype. We sought to define the genotype-specific electrophysiological phenotype of PLN R14del cardiomyocytes and evaluate how modulation of the transient outward potassium current and late sodium current alters arrhythmic risk.

At least 50% of individuals who suffer sudden cardiac arrest (SCA) have warning symptoms before their SCA, but these are not sufficient to predict imminent SCA (ISCA). We hypothesized that combining symptoms with clinical profile could effectively predict ISCA.

Catheter ablation is an essential tool for ventricular arrhythmia management, yet sustained procedural success is hindered by the limited ability to identify nonendocardial arrhythmogenic substrates during the procedure. Although delayed enhancement cardiac magnetic resonance imaging is the reference standard for detecting myocardial fibrosis, barriers including cost, workflow complexity, and artifacts in patients with implantable devices limit its preprocedural use. We hypothesized that intracardiac electrograms provide sufficient information to infer scar beyond the endocardial surface and that this information can be harnessed by machine learning techniques.

GLP-1 (glucagon-like peptide-1) receptor agonists (RAs) have emerged as a major therapeutic advance in cardiometabolic medicine. Initially developed as glucose-lowering therapies for type 2 diabetes, these agents have demonstrated broad benefits that extend well beyond glycemic control. GLP-1 RAs enhance glucose-dependent insulin secretion and reduce appetite, leading to improved glycemia and sustained weight loss. In addition, GLP-1 signaling exerts vascular and myocardial effects, including improved endothelial function, reduced inflammation and oxidative stress, and favorable changes in cardiac metabolism and remodeling. Large randomized cardiovascular outcomes trials have consistently shown that several GLP-1 RAs reduce major adverse cardiovascular events, including myocardial infarction, stroke, cardiovascular death, and heart failure. Benefits have been observed across diverse populations, including individuals with established cardiovascular disease and those with obesity but without diabetes. Emerging therapies targeting multiple incretin pathways, such as dual GIP (glucose-dependent insulinotropic polypeptide)-GLP-1 RAs, may further extend these benefits. Collectively, these findings suggest that GLP-1 RAs influence multiple cardiometabolic pathways and may shift the underlying metabolic milieu toward a more favorable physiological state. In this Clinical Primer, we review the physiology of GLP-1 signaling, the evidence supporting cardiovascular risk reduction, and practical considerations for the clinical use of incretin-based therapies.

Dilated cardiomyopathy (DCM) is associated with shifts in cardiac metabolism. However, those shifts vary widely across patients, likely reflecting the diverse underlying causes of the disease. Identifying metabolic subtypes, or metabotypes, in DCM patients could help tailor treatments to patient needs. Hence, having a practical approach to identify these metabotypes would be a significant advance toward precision medicine in DCM.

Cardiorespiratory fitness (CRF) is a strong predictor of mortality and noncommunicable disease risk, but its underlying molecular mechanisms are poorly understood. In this study, we identified 2 signatures of CRF (1 metabolomic and 1 proteomic) from UK Biobank participants who completed a risk-stratified submaximal cycle ergometer test, with CRF estimated from the heart rate response to incremental workload.

Clinical genetic testing is now the standard of care for cardiomyopathy, guiding risk stratification, clinical management, and earlier diagnosis in family members. Yet, a large proportion of the genetic basis of cardiomyopathy remains incompletely explained. Prior efforts to identify genetic causes of cardiomyopathy have largely focused on coding DNA sequence, which accounts for only 3% of the human genome, leaving the noncoding regulatory sequence space relatively unexplored. A confluence of emerging technologies is now transforming our capability to identify and interpret noncoding variants. This review summarizes the field's current knowledge of how noncoding variants influence the development of cardiomyopathy, both from the standpoint of rare Mendelian disease variants and population-level risk alleles. In addition, we describe how new technologies have enabled systematic identification and prioritization of regulatory regions that govern gene expression. Beyond identification of regulatory regions, we discuss how causal testing of variants is now possible at an unprecedented scale through massively parallel reporter assays, allowing both detailed mapping of these regions and efficient validation of variants discovered through genome-wide association studies. Finally, we review deep learning approaches that hold the potential for genome-wide noncoding variant interpretation. Together, this review highlights strategies for large-scale interpretation of noncoding variants while also demonstrating the clear need for extension of clinical variant adjudication workflows to the noncoding genome to fully take advantage of increasingly available whole-genome sequencing data.