The "2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia" retires and replaces the "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol."

The purpose of this study was to prospectively validate the MIRACLE2 score in the GLOBAL-MIRACLE registry, a multicenter, international, prospective registry of patients admitted with resuscitated out-of-hospital cardiac arrest of presumed cardiac cause.

Peripheral artery disease (PAD) and its severe form, chronic limb-threatening ischemia (CLTI), significantly impair blood flow to the lower extremities, affecting millions of adults globally. Intramuscular adipose tissue (IMAT) and fibrosis accumulation distinguish patients with CLTI from those with mild PAD, suggesting a role in CLTI pathobiology. However, the functional consequences of IMAT in CLTI remain unclear.

The arterial vasculature is the second most frequently calcified structure in the human body after the skeleton. Calcification of the aorta and aortic valves occurs in most individuals in westernized societies with advancing age, with abdominal aortic calcification generally preceding ascending thoracic aortic disease. In cardiac valves and the thoracic aorta, however, calcification often arises earlier in common disease contexts characterized by metabolic, mechanical, or inflammatory injury (eg, metabolic syndrome, chronic kidney disease, irradiation). In these settings, calcification frequently involves the arterial media as a histoanatomic feature, and is associated with accelerated neurocognitive decline and increased cardiovascular mortality, reflecting a form of precocious aging. The term arteriosclerosis was coined nearly 2 centuries ago to describe the calcium-mediated hardening of the aorta and conduit arteries observed at autopsy with aging. However, much of our understanding of the causes, characterization, and consequences of aortic calcium deposition has emerged only within the past decade. Features of disease biology, including engagement of innate immunity, senescence (inflammaging), and ectopic activation of osteogenic mechanisms, are consistently revealed. In this article, we briefly review the burgeoning literature, highlighting recent advances in clinical and discovery science with translational implications. Given the current trajectory, after 2 centuries of disease recognition, the next decade of innovation promises meaningful progress toward effective medical treatments to prevent and treat the clinical consequences of calcific aortopathy.

Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM), and have been associated with worse prognosis. However, it is unclear how comorbidities influence clinical trajectories, the timing of events, and causes of death in sarcomeric and nonsarcomeric HCM.

Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal. Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair. YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic remodeling to overcome the cardiomyocyte proliferation barrier and enable cardiac regenerative repair after heart injury.

Aortic valve calcification increases leaflet stiffness and contributes to the development of calcific aortic valve disease. The molecular and cellular mechanisms underlying calcification remain unclear. Here, we aimed to investigate the role of PRMT3 (protein arginine methyltransferase 3) in valvular calcification and calcific aortic valve disease progression.

Right ventricular failure drives both morbidity and mortality in pulmonary arterial hypertension (PAH), but the mechanism of transition from compensated right ventricle (cRV) to decompensated RV (dRV) is unknown, and some PAH patients develop dRV faster than others.

Myocardial ischemia/reperfusion (I/R) injury is a common and severe clinical complication in patients with ischemic heart disease after reperfusion therapy. Effective therapeutic strategies for myocardial I/R injury remain limited. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. However, the mechanisms underlying ferroptosis in myocardial I/R injury are not fully understood.

Background: Angiography-derived fractional flow reserve (Angio-FFR) is an emerging tool for guiding percutaneous coronary intervention (PCI). Its uptake and outcomes compared to pressure wire (PW)-based assessment in the US are unknown. Methods: We conducted a cohort study of US Medicare beneficiary data from 1 January 2019 to 31 December 2024. Propensity score matching (1:3) of Angio-FFR to PW was performed in patients who underwent PCI during the same procedure, and separately among those who did not undergo PCI during the same procedure. The primary outcome was the cumulative incidence of major adverse cardiovascular events (MACE) through 2 years, including all-cause death, myocardial infarction (MI) and repeat revascularization. Secondary outcomes included individual MACE components, 30-day acute kidney injury and 30-day major bleeding. Falsification endpoints (hospitalization for pneumonia and hip fracture) were used to assess unmeasured confounding. Results: Of 466,535 angiograms that included intra-procedural physiologic assessment, 1.00% (N=4,672) used Angio-FFR. Annual use increased from 0.47% in 2019 to 3.85% in 2024. Among PCI patients, 1,591 Angio-FFR and 4,773 PW matched PCI patients had similar MACE rates through 2 years (24.8% vs 23.5%; HR 1.01, 95% CI 0.85 - 1.20). Secondary outcomes and falsification endpoints were not significantly different. In non-PCI patients, 2,532 Angio-FFR and 7,596 PW matched patients also had similar MACE through 2 years (24.1% vs 23.9%; HR 0.97, 95% CI 0.84 - 1.11). Conclusions: Angio-FFR usage in the US is modest but increasing. Angio-FFR guidance during angiography versus PW was associated with comparable outcomes through 2 years.

Background: Although guidelines recommend invasive management for non-ST-elevation myocardial infarction (NSTEMI), there is considerable variability in the application of these recommendations across different hospitals, reflecting a lack of standardized clinical pathways and highlighting ongoing uncertainty in real-world practice. We sought to describe site-level variability in the use and timing of invasive angiography for NSTEMI and their association with in-hospital outcomes. Methods: Using NCDR Chest Pain-MI registry data (2019-2024), the rates and timing of invasive coronary angiography, if any, were characterized among patients with NSTEMI. Hierarchical logistic regression models were created to describe hospital-level variability in management using median odds ratios (MORs), adjusted for patient and site characteristics. Inverse probability weighting was used to estimate the association between treatment strategy and in-hospital outcomes. Results: We included 287,275 patients with Type-1 NSTEMI from 541 hospitals (age 67.6±13.3 years, 36.4% women). Invasive coronary angiography was performed in 87.1%, of whom 56.9% within 24 hours. Among those treated invasively, 66.1% received percutaneous coronary intervention. Older patients with more comorbidities were paradoxically more likely to receive conservative management or delayed intervention (>24 hours). Site-level variability for invasive strategy (vs. conservative) was large [MOR 2.85 (2.64-3.10)], as was early invasive treatment [MOR 1.67 (1.62-1.74)], particularly on weekends/holidays [MOR 1.89 (1.81-1.98)]. The use of any invasive strategy was associated with lower in-hospital mortality versus conservative management [weighted OR 0.36 (0.31-0.42)]. This finding was consistent across all baseline risk categories (P-interaction <0.001). Conclusions: Patients with Type-1 NSTEMI and higher-risk clinical profiles were not consistently prioritized to undergo early invasive management with substantial variability across hospitals. Invasive management was associated with lower in-hospital mortality compared with conservative treatment. Future randomized studies in the modern PCI era are needed to confirm our findings, and identify which patients benefit most and when intervention should occur.

Moderate and severe tricuspid regurgitation (TR) is associated with poor outcomes, yet current grading systems do not fully capture circulatory heterogeneity. We investigate the relationship of cardiac index (CI) with rest-exercise hemodynamics, metabolic and inflammatory profiles, and clinical outcomes in moderate and severe TRs.

There is limited evidence of the relationship between aortic and iliac calcification and aortic events (aortic dissection or aneurysm rupture) and major adverse limb events (MALEs; peripheral revascularization and lower limb amputation). The aim of this population-based prospective cohort study was to investigate the association of aortic and iliac calcifications with aortic events and MALEs.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is useful for identifying ventricular tachycardia (VT) substrate in patients with structural heart disease. While preprocedural LGE-CMR is widely used for planning, the role of postprocedural LGE-CMR in evaluating VT ablation success and long-term scar evolution has been less explored. This study aimed to prospectively and systematically assess the long-term evolution of scar and ablation lesions using serial postablation LGE-CMR with long-term follow-up.

Nutrition insecurity is a major driver of poor cardiovascular health in Indigenous communities. Medically tailored meals may improve heart failure outcomes and quality of life. There is growing momentum among Indigenous communities to reclaim traditional precontact foods to improve cardiovascular health. In this context, utilizing community-based-participatory methods, we designed MUTTON-HF (Medically Utilized Tailored Traditional Foods to Optimize Nutrition in Heart Failure)-an Indigenous culturally and medically tailored meals program that locally sources Native produce and meat and incorporates traditional Diné (Navajo) foods and recipes.

Mortality from acute myocardial infarction (MI) has declined significantly in the past decade for nondiabetic patients. However, both morbidity and mobility of ischemic heart failure (IHF) persistently escalate in the diabetic population via incompletely understood mechanisms. Recent studies demonstrated that small extracellular vesicles (sEVs) released from nondiabetic and diabetic adipocytes (ADps) exert opposite effects on acute myocardial ischemia and reperfusion (MI/R) injury. However, whether and how ADp sEVs may protect against post-MI remodeling and IHF, and more important, whether and how diabetes may impair this protective effect, remain unknown.

Ischemic heart disease remains a leading cause of mortality worldwide, with adverse remodeling after myocardial infarction driven by inflammation and cardiomyocyte loss. Although cytotoxic lymphocytes exacerbate myocardial injury and P16 marks cellular senescence in diseased hearts, the cell type-specific functions of P16+ populations remain unclear.

Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb events (MALE) and major adverse cardiovascular events. The VOYAGER-PAD trial demonstrated that rivaroxaban 2.5 mg twice daily on top of antiplatelet therapy significantly reduced this risk. Whether the risk of major adverse cardiovascular events and MALE and the effect of rivaroxaban are consistent in patients with a history of prior LER versus those without has not been described.

Atrial fibrillation (AF) is associated with reduced quality of life and frequent hospitalizations. Integrated nurse-led care (NLC) has proven beneficial in unselected AF patients, but evidence specific to patients undergoing catheter ablation is limited. We aimed to assess the impact of a structured nurse-led intervention in patients undergoing first-time AF ablation.

A genotype-guided de-escalation strategy-switching from a potent P2Y12 inhibitor to clopidogrel-may reduce bleeding risk in patients with acute coronary syndrome (ACS). This analysis evaluated the safety and effectiveness of routine genetic testing to guide antiplatelet therapy in clinical practice.