MGP (matrix Gla-protein), a known inhibitor of vascular calcification, becomes biologically active by vitamin K-dependent carboxylation. Circulating levels of dpucMGP (dephospho-uncarboxylated matrix Gla-protein), the inactive form of MGP, have been associated with large artery stiffening and reduced skeletal muscle mass in heart failure (HF). Whether dpucMGP is related to adverse outcomes in patients with HF is unknown.

TRPC6 (transient receptor potential canonical 6) channels, encoded by the TRPC6 gene, are widely expressed in cardiomyocytes and play a critical role in maintaining intracellular Ca2+ homeostasis. Variants in TRPC6 are associated with chemotherapy-related cardiomyopathy. Specifically, the TRPC6 A404V polymorphism, with a minor (404 V) allele frequency of 12% in the general population, has been identified in patients undergoing anthracycline therapy. However, the underlying mechanisms remain largely unexplored.

Cardiovascular disease is the number 1 killer in industrialized countries, with sudden cardiac death due to ventricular arrhythmias representing a major component. To reduce sudden cardiac death, accurate risk prediction and development of effective preventive treatments remain major challenges. In this study, we explored the possibility of using a population-based computational modeling approach to perform virtual clinical trials for antiarrhythmic drug discovery and drug safety testing.

In vitro functional modeling of genetic variants has revolutionized our understanding of which variants can cause cardiac disorders, providing insights into their molecular underpinnings. This review provides an overview of high-throughput methods used for the functional assessment of variants implicated in inherited cardiac diseases. Advances in gene-editing technology now enable the efficient generation of cells expressing individual genetic variants or libraries of variants for robust functional studies. We discuss innovative assays that can evaluate dozens or hundreds of variants sequentially. For example, the electrophysiological properties of numerous cardiac ion channel variants in genes linked to inherited arrhythmias can be characterized using automated patch clamping. The mechanical properties of cardiomyocytes expressing candidate cardiomyopathy variants can be assessed using techniques such as atomic force microscopy, traction force microscopy, and impedance-based methods. Multiplexed assays of variant effect are an emerging family of techniques that use gene-specific or general assays, combined with next-generation sequencing, to characterize hundreds or thousands of pooled genetic variants. We examine the key advantages and limitations of each method and outline future goals for the field. Innovative in vitro studies of cardiac genetic variants will enhance our understanding of variant-disease relationships and improve diagnosis, screening, and treatment options for these disorders.

Takayasu arteritis (TAK) is a rare, immune-mediated large-vessel vasculitis that affects predominantly young women and carries a substantial risk of both vascular complications and long-term cardiovascular disease. Although glucocorticoids and conventional immunosuppressive therapies remain the cornerstone of treatment, relapse rates are high, and current strategies fail to adequately mitigate future cardiovascular risk. This review synthesizes evidence on current treatment strategies, unmet clinical needs, and novel approaches, including immunological and vascular-targeted therapies, and argues for a shift in management paradigm toward integrated cardiovascular risk reduction. We discuss advances in understanding the pathogenesis of TAK, highlighting the roles of innate and adaptive immunity in disease progression, and the challenges of early diagnosis and disease monitoring. We critically appraise current treatment paradigms, including glucocorticoids, conventional disease-modifying antirheumatic drugs, and biologics such as tocilizumab and tumor necrosis factor-α inhibitors, and outline emerging therapies targeting novel pathways, including interleukin-17, interleukin-12/23, Janus kinase/signal transducer and activator of transcription, and Notch-1/mammalian target of rapamycin complex signaling. We highlight the increasing recognition of cardiovascular morbidity as a major contributor to mortality in TAK and the need for integrated approaches to risk factor modification. We explore a road map for advancing management of cardiovascular disease in TAK, including comprehensive screening tools that integrate serological and imaging biomarkers to interrogate cardiovascular risk and potential therapeutic cardioprotective strategies such as sodium-glucose cotransporter 2 inhibitors and endothelin receptor antagonists. Despite recent progress, clinical management remains limited by diagnostic uncertainty, heterogeneous treatment approaches, and a paucity of high-quality randomized controlled trials. Future work should focus on interventions that target both immune-mediated vascular injury and cardiovascular disease progression. Achieving long-term disease remission while reducing cardiovascular mortality must become the primary therapeutic goal in TAK.

ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Arrhythmogenic cardiomyopathy (ACM) is a fatal genetic heart disease primarily caused by mutations in desmosomal genes, leading to impaired cell-cell adhesion, ventricular arrhythmias, and progressive heart failure. Although gene therapy for specific ACM populations shows promise, it remains unclear whether mutation-agnostic pathways dysregulated across desmosomal mutations could be exploited for therapeutic intervention in this genetically broad and severe population. The reduction in expression of the ventricular gap junction protein Cx43 (connexin-43) is a common molecular alteration underlying desmosomal junctional deficits and arrhythmias, suggesting a potential common underlying mechanism and a therapeutic target for ACM. We hypothesized that restoration of Cx43 expression could be a mutation-agnostic intervention for ACM.

Pathogenic SCN5A variants are associated with inherited arrhythmias such as long-QT syndrome, Brugada syndrome, and sick sinus syndrome. While Nav1.5, an α-subunit of the cardiac sodium channel encoded by SCN5A, has been considered to function as a monomer, recent studies reveal that a reduction of sodium current in wild-type Nav1.5 can be caused by dimerization with loss-of-function mutated Nav1.5 through dominant-negative effects. However, the clinical significance of the dominant-negative effect remains unclear.

Discontinuing statin therapy before pregnancy remains challenging, especially in high-risk women. We evaluated the risks of maternal cardiovascular, gestational, and fetal outcomes associated with continuing versus discontinuing statin therapy before the last menstrual period (LMP).

The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events.

Transthyretin amyloid cardiomyopathy (ATTR-CM) causes a restrictive cardiomyopathy resulting in heart failure (HF). Signaling pathways associated with ATTR-CM are not well defined. The purpose of this study was to identify signaling pathways that are dysregulated in ATTR-CM compared with controls.

To investigate the proteomic signatures of heart failure (HF) in diabetes. The underlying mechanisms of the elevated risk of HF in diabetes are unknown.

Long-term outcomes after Fontan vary widely. Although pre-Fontan hemodynamics predict early failure, their association with long-term outcomes remains unclear. We hypothesized that pre-Fontan hemodynamics predict long-term risk of death or transplantation.

Tricuspid regurgitation (TR) leads to systemic venous congestion and congestive hepatopathy, but conventional TR imaging parameters incompletely capture systemic consequences. Hepatic extracellular volume fraction (ECV) on cardiac magnetic resonance T1 mapping may reflect hepatic tissue remodeling and provide prognostic information beyond conventional risk markers.

Computed tomography based planimetric assessment of the anatomic aortic valve area (aAVACTA) in aortic stenosis is routinely performed. Unlike transthoracic echocardiography (TTE)-based effective AVA by TTE, it lacks clearly defined severity cutoff values, limiting clinical utility.

Polycystic ovarian syndrome (PCOS) is associated with increased cardiovascular morbidity and a higher risk of atherosclerotic cardiovascular disease. PCOS has been associated with electrocardiographic alterations. However, the potential long-term risk of cardiac arrhythmias in women with PCOS remains insufficiently investigated.

Atrial secondary mitral regurgitation (aSMR) is a distinct subtype of SMR characterized by normal leaflets, annular dilatation, left atrial (LA) enlargement, and preserved left ventricular function. Treatment pathways for aSMR are undefined, and limited data exist regarding outcomes following mitral transcatheter edge-to-edge repair (MTEER). The analysis aimed to evaluate outcomes in patients with aSMR treated with MTEER from the EXPANDed (Evaluation of the MitraClip X System Post-MArket Real-World CliNical Outcomes Database ) studies.

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome that often presents diagnostic challenges due to its diverse causes and overlapping symptoms with other conditions. Its prevalence is increasing, driven by an aging population and rising associated comorbidities including obesity, diabetes, and hypertension. Echocardiography is a cornerstone in the screening and diagnosis of HFpEF due to its noninvasive nature, accessibility, and ability to provide a comprehensive cardiac assessment. Cardiac magnetic resonance can further enhance diagnostic accuracy and be a useful tool in follow-up. Cardiac magnetic resonance tissue characterization by parametric mapping sequences (T1/T2 mapping, late gadolinium enhancement, extracellular volume quantification, myocardial flow reserve, and myocardial strain) is also helpful in evaluating specific conditions that can lead to symptoms of heart failure in the setting of normal ejection fraction. The role of cardiac magnetic resonance has become increasingly important with the emergence of new therapies, as distinguishing HFpEF causes is essential for precise therapy selection. In this review, we describe the diagnostic imaging features associated with HFpEF, along with the potential role of imaging in follow-up. We also propose a diagnostic workflow for suspected HFpEF cases in clinical practice.

The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

Transcatheter edge-to-edge repair is an established treatment for tricuspid regurgitation (TR) in nonoptimal surgical candidates. Two techniques have been described: zipping (or bicuspidization) and clover (or triple-orifice). This study aimed to compare the echocardiographic and clinical outcomes of these 2 techniques.