A domain of CMYA5 (RID) is a novel RYR2 regulator. RID overexpression reduced arrhythmias in CPVT disease models.

During the past 75 years, advances in cardiovascular science and technology have significantly reduced morbidity and mortality. In 2012, Drs Nabel and Braunwald reviewed this progress in A Tale of Coronary Artery Disease and Myocardial Infarction, highlighting the landmark innovations that contributed to the decline in cardiovascular death rates from 1950 to 2010. Since then, groundbreaking developments in pharmacologic therapies, interventional procedures, surgical techniques, and molecular medicine-including gene editing and RNA-based treatments-have emerged. However, despite these innovations, improvements in cardiovascular mortality have stalled, driven not only by epidemiologic shifts but also by persistent inequities in implementation. This article examines the past 15 years of progress in cardiovascular medicine and proposes a forward-looking roadmap focused on prevention, responsible innovation, and thoughtful health care delivery to ensure technological advancements translate into improved health outcomes for all.

As an iron-dependent form of regulated cell death caused by lipid peroxidation, ferroptosis has been implicated in ischemic injury, but the underlying mechanisms in acute myocardial infarction (AMI) remain poorly defined. ALDH2 (acetaldehyde dehydrogenase 2) catalyzes detoxification of lipid aldehydes derived from lipid peroxidation and acetaldehydes from alcohol consumption. The Glu504Lys polymorphism of ALDH2 (rs671, ALDH2*2), affecting ≈40% of East Asians, is associated with increased risk of myocardial infarction (MI). This study aims to investigate the role of ALDH2*2 and ferroptosis in AMI.

The Target Stroke Phase III program is a national quality improvement initiative led by the American Heart Association, which sought to improve the quality of care for patients with acute stroke undergoing acute reperfusion therapy including endovascular thrombectomy (EVT).

Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiac disorder marked by left ventricular hypertrophy and hypercontractility. This excessive mechanical workload creates an energetic mismatch in which consumption exceeds production, leading to myocardial energy depletion. Although CK (creatine kinase) plays a key role in cardiac energy homeostasis, its involvement in HCM remains unclear. This study investigates how hypercontractility-driven mitochondrial stress and the resulting increase in mitochondrial H2O2 disrupt CK function in HCM.

Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis that confers increased risk of atherosclerotic cardiovascular disease. Measured by noncontrast cardiac computed tomography, CAC improves risk stratification beyond traditional risk factors and can aid decision-making for allocation of preventive treatments. Although national guidelines recommend consideration of CAC measurement for >17 million individuals in the United States with borderline to intermediate 10-year atherosclerotic cardiovascular disease risk, adoption has been limited. A promising approach to bridge this gap is opportunistic detection of CAC using non-ECG-gated chest computed tomography scans that are performed for a noncardiac indication. Approximately 19 million non-ECG-gated chest computed tomography scans are performed per year, and reporting opportunistic detection of CAC from these scans can enhance atherosclerotic cardiovascular disease risk stratification without additional radiation exposure, cost, or burden. Estimation of risk by traditional risk factor scoring is underused, and reporting of opportunistic detection of CAC has the potential to alert physicians of risk, independent of guideline-recommended risk calculator use. Advancements in artificial intelligence allow integration of automated CAC quantification into clinical practice. Several artificial intelligence algorithms are in use to improve the likelihood of reporting opportunistic detection of CAC and appropriate allocation of preventive therapies. Systematic approaches are needed to ensure appropriate reporting, interpretation, and action while avoiding unnecessary downstream testing. Implementation that includes tailored preventive care and streamlined care pathways involving multidisciplinary clinical teams including radiology, cardiology, and primary care is essential.

BMP10 (bone morphogenetic protein 10) is a ligand of the TGF (transforming growth factor) β superfamily secreted mainly by atrial cardiomyocytes. Elevated BMP10 blood concentrations predict atrial fibrillation (AF), AF recurrence after ablation, and AF-related cardiovascular complications like stroke. The conditions increasing BMP10 secretion and the downstream effects of BMP10 in cardiomyocytes are poorly understood. We assessed BMP10 secretion dynamics and BMP10 effects in a human 3-dimensional model of atrial and ventricular engineered heart tissue (EHT).

In a universal health care system, geographic disparities in atrial fibrillation (AF) outcomes remain poorly understood. This study aimed to evaluate rural-urban differences in clinical outcomes among patients presenting to the emergency department (ED) with AF.

Ventricular electrogram duration map (VEDUM) is a new approach for the identification of the arrhythmogenic substrate critical for ventricular tachycardia (VT), and it is based on the evaluation of the prolonged bipolar electrograms. Our aim is to evaluate the prognostic role of the VEDUM area in patients with VT and ischemic cardiomyopathy.

Cardiac rehabilitation (CR) is a proven intervention to improve cardiovascular health, offering benefits such as reduced hospital readmission rates, lower mortality rates, and enhanced quality of life. Poor CR participation, which is a universal problem, is particularly pronounced in women. Considerable sex and gender disparities exist in CR access, engagement, and outcomes. Despite the effectiveness of CR, women are underrepresented in CR programs, and face barriers related to lower referral rates, medical comorbidities, societal roles, and financial constraints. These challenges are further compounded by racial and ethnic disparities. Women also have greater needs for specific aspects of CR, including mental health support and social integration. Traditional CR programs often fail to address these needs adequately, contributing to proportionally lower participation and completion rates among eligible women. Further research is needed to assess the efficacy of CR programs in women, including women from underrepresented racial or ethnic groups, and to identify optimal CR approaches in specific populations, such as people with spontaneous coronary artery dissection, ischemia, myocardial infarction with nonobstructive coronary arteries, or stress-induced cardiomyopathy. To optimize CR participation and outcomes in women, a multifaceted approach is required. Strategies such as automatic referral systems, gender-sensitive program design, and mental health integration are essential. Further research is needed to determine the impact of nontraditional delivery models on women's cardiovascular health. Addressing these gaps can lead to improved cardiovascular health and quality of life for women with cardiovascular disease.

Inappropriate sinus tachycardia (IST) is an arrhythmia characterized by rapid sinus rates of over 100 bpm at rest. The mechanisms underlying this often-debilitating condition are not fully understood. The differential diagnosis for this persistent observation is broad, including medication side effects or serendipitous use of chronotropic stimulating drugs. Genetic causes of IST are seldom considered. Only 2 mutations have been linked to this condition, both of which affect the gene encoding HCN4 channels, which play an important role in generating pacemaker activity of the sinoatrial node.

In nonischemic cardiomyopathy, mitochondrial Ca2+ handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca2+ release. Recently, it has been reported that lysosomal Ca2+ release can trigger an SR Ca2+ release. We investigated whether lysosomal Ca2+ flux through the TRPML1 (transient receptor potential mucolipin 1) channel could contribute to ischemic cardiomyopathy-related arrhythmia by causing diastolic SR Ca2+ release.

Fontan conversion (FC) is associated with a lower risk of atrial arrhythmias and thromboembolism, but it is unknown whether FC improves long-term survival. The purpose of this study was to assess the impact of FC on transplant-free survival.

Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy is safe and reduces ventricular arrhythmia burden. Previous studies included adult patients, and data on pediatric patients are scarce. The objective of our study was to report on the safety and efficacy of RFCA in pediatric arrhythmogenic right ventricular cardiomyopathy.

Novel biodegradable patent foramen ovale (PFO) closure devices offer a promising therapeutic option. The efficacy and safety of the novel biodegradable devices compared with nitinol devices have not yet been investigated in a randomized clinical trial.

Unlike the tremendous progress made in atrial fibrillation ablation, the greatest unmet clinical need is for innovative ablation treatments for scar-related ventricular tachycardia (VT), particularly given the thick, often fibrotic tissue characteristic of the scarred substrate. A focal pulsed field ablation (PFA) catheter with a novel waveform was designed: high voltage to provide tissue penetration and low energy (using short-duration pulses) to avoid tissue overheating. We present the outcomes of VCAS (Ventricular Catheter Ablation Study), a first-in-human study of this PFA catheter to ablate scar-related VT.

The potential J-shaped relationship whereby lower diastolic blood pressure (DBP) is associated with a higher risk of adverse cognitive outcomes has raised concerns regarding intensive systolic blood pressure (SBP) lowering. However, the current guidelines advocate a stricter SBP target of <130 mm Hg, with no clear consensus on a DBP target, especially with respect to brain health. The present study aimed to determine the relationship between treated DBP and cognitive function, as well as cerebral perfusion and structure, in adults who achieved an SBP <130 mm Hg.

The Minima Stent System is the first stent designed, tested, and Food and Drug Administration-approved for use in neonates, infants, and children. Our objective was to evaluate the safety and efficacy of Minima implantation for pulmonary artery stenosis (PAS) and coarctation of the aorta (CoA).

Although cardiovascular disease is the leading cause of death in the United States among Medicare beneficiaries, management of modifiable risk factors remains suboptimal. Medicare Advantage (MA) enrollment has increased substantially; therefore, understanding the quality of cardiovascular risk factor management in MA is critical. In this study, we evaluated whether cardiovascular risk factor management was better among MA compared with traditional Medicare (TM) beneficiaries.

Psychosocial stress is linked to the development of cardiovascular disease, with a more pronounced impact in female participants. This study investigates sex differences in the association between perceived stress and myocardial tissue characteristics, as assessed by cardiovascular magnetic resonance imaging, and evaluates the contribution of psychosocial burden, including caregiving and perceived social standing.