Calcified nodules (CNs) represent a high-risk coronary lesion phenotype associated with target lesion revascularization (TLR). Although rotational atherectomy (RA) is an established treatment for calcified lesions, its benefit for CNs remains unclear. This study aimed to evaluate the impact of RA on TLR and to identify specific morphological features on intravascular ultrasound that may influence its therapeutic effect for CNs.

Risk prediction has been used in the primary prevention of cardiovascular disease for >3 decades. Contemporary cardiovascular risk assessment relies on multivariable models, which integrate established cardiovascular risk factors and have evolved over time from the Framingham Risk Model to the pooled cohort equations to the PREVENT (Predicting Risk of CVD Events) equations. Recent scientific (ie, genomics, proteomics, metabolomics) and methodologic (ie, artificial intelligence) advances have led to a proliferation of novel models, biomarkers, and tools for potential use in risk prediction. In parallel, the growing armamentarium of preventive therapies, some with considerable cost, underscores the need for more accurate and precise risk assessment to prioritize those at highest risk who will derive the greatest absolute benefit. Accompanying the considerable enthusiasm for the potential of newer approaches to improve risk prediction is the need for rigorous evaluation and assessment of their performance (ie, accuracy, precision, incremental performance when added to contemporary multivariable risk models or established risk factors) and clinical utility (ie, actionability, scalability, generalizability) before adoption in clinical practice. Additional considerations in risk tool evaluation include reproducibility, cost-value considerations (including impact on downstream health care costs), and implications for health equity. This scientific statement defines a standardized framework for general considerations in risk prediction, statistical assessment of predictive utility, and critical appraisal of clinical utility and readiness. This scientific statement is intended to support clinicians, researchers, and policymakers in how best to evaluate current and emerging risk prediction tools and ultimately improve the prevention of cardiovascular disease in diverse populations.

During myocardial infarction (MI), M1-like macrophages exacerbate myocardial injury by excessively secreting inflammatory cytokines. Therefore, modulating the activity of M1-like macrophages may represent a novel therapeutic strategy for MI. PRMTs (protein arginine methyltransferases) primarily regulate protein function via asymmetric dimethylation, but PRMT9 does so through symmetric dimethylation. However, its role in cardiovascular diseases has yet to be established. In this study, we investigated the role of PRMT9 in macrophage polarization in the context of MI and explored its therapeutic effect for MI.

Limited data are available regarding the relative rates, etiology, and long-term prognostic implications of spontaneous myocardial infarction (MI) after percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery for left main coronary artery disease (LMCAD).

Genetic variation affects clinical outcomes, prognosis, and family planning decisions in individuals with congenital heart disease (CHD). While genetic testing recommendations for infants and children with CHD have expanded, similar broad guidelines are lacking for patients with adult CHD (ACHD). Here, we investigated the current state of genetic testing in patients with ACHD and their perceptions toward testing, which has not been previously reported.

Clonal hematopoiesis (CH), the benign clonal expansion of hematopoietic stem cells, is often caused by somatic sequence variations in genes associated with hematologic malignancies. Over the past decade, CH has emerged as a risk factor for a wide range of cardiovascular diseases (CVDs), including atherosclerosis, heart failure, atrial fibrillation, and thrombosis. The cardiovascular risk associated with CH is heterogeneous; it varies on the basis of specific genes and variants, clone size, and various extrinsic features. Mechanistic studies suggest that CH contributes to CVDs through both gene-specific pathways and broader inflammatory processes. These include aberrant cytokine production, inflammasome activation, and other proinflammatory mechanisms, which can accelerate atherosclerosis, promote thrombogenesis, and impair vascular or myocardial function. These findings underscore the importance of addressing CH as a potential contributor to CVDs. CH is predominantly considered an age-related phenomenon, but lifelong influences on the fitness of genetic variants, including germline predispositions, obesity, chronic inflammation, and exposure to environmental toxins (eg, tobacco, certain cancer treatments), influence CH. A greater understanding of CH risk factors is therefore important for both individual and population-level risk assessments. Incorporating CH-associated risk into existing CVD risk prediction models may inform new personalized preventive or therapeutic approaches. No CH-specific therapies have proven efficacy in CVD treatment or prevention, but multiple molecular-based therapeutic hypotheses are beginning to be tested.

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is a potent cholesterol-lowering strategy. This study examined the effects of PCSK9 monoclonal antibodies (mAbs) and high-intensity statins beyond low-density lipoprotein cholesterol reduction, which are not fully defined, particularly in patients with acute myocardial infarction (MI).

Stressor-associated atrial fibrillation (AF), defined as newly diagnosed AF in the setting of a reversible physiological stressor, is common. However, risk factors, outcomes, and current management practices remain poorly understood.

Btk (Bruton's tyrosine kinase), a Tec-family kinase initially recognized for its role in B-cell signaling, has emerged as a critical player in thrombosis and cardiovascular disease. Beyond the established therapeutic effects of Btk inhibitors in B-cell malignancies, its expression in platelets, macrophages, and neutrophils implicates Btk in platelet activation, atherothrombosis, and innate immunity. This state-of-the-art review synthesizes the current understanding of Btk's mechanistic contributions to thrombosis and cardiovascular disease, evaluates the evolution of Btk inhibitors (BTKi), and explores their therapeutic potential. Patients with X-linked agammaglobulinemia who lack Btk do not have a bleeding diathesis, indicating that platelet-selective Btk inhibition would be a safe antithrombotic strategy. In platelets, Btk mediates immunoreceptor tyrosine-based activation motif-dependent and -independent signaling, driving atherothrombosis, venous thrombosis, and immunothrombosis without affecting hemostatic platelet functions. In myeloid cells, Btk amplifies inflammation via NLRP3 inflammasome activation and neutrophil extracellular trap formation, linking it to thromboinflammation and atherosclerosis. First-generation BTKi such as ibrutinib demonstrate antithrombotic efficacy but are limited by off-target effects, including bleeding and atrial fibrillation. Second- and third-generation inhibitors (eg, acalabrutinib, zanubrutinib, and pirtobrutinib) show enhanced selectivity, reducing cardiovascular toxicity in patients with B-cell malignancies. Highly selective BTKi (fenebrutinib and remibrutinib) do not show bleeding in clinical trials of various autoimmune disorders, and covalent selective BTKi applied at low dosage are expected to selectively inhibit Btk in platelets without bleeding side effects. Preclinical data and early observations from compassionate use in patients with atypical autoimmune thrombosis highlight the potential of BTKi as selective antithrombotic agents beyond traditional therapies. This review conceptualizes and underscores Btk's pivotal role at immune-thrombosis interfaces in atherothrombosis, advocating for precision medicine approaches and innovative platforms to unlock its full therapeutic potential in cardiovascular disease management.

Circulating proteins represent robust drug targets with therapeutic potential. Many discoveries have focused on European-ancestry populations, disregarding minuscule yet substantial proteomic differences that may contribute to disease and alter drug generalizability in other ancestry groups.

There is an emerging convergence between atherosclerotic cardiovascular disease and cancer, driven by shared risk factors and overlapping pathophysiologic mechanisms. Traditional factors, such as smoking, aging, obesity, hypertension, and diabetes, alongside novel markers, such as clonal hematopoiesis of indeterminate potential, not only predispose individuals to both malignancies and coronary atherosclerosis but also amplify the risk of cardiotoxicity from cancer therapies. Inflammatory processes play a central role in atherogenesis, a process further accelerated by oncologic treatments-including chemotherapy (eg, anthracyclines, 5-fluorouracil), targeted and hormone therapies (eg, tyrosine kinase inhibitors, androgen deprivation, aromatase inhibitors), immune checkpoint inhibitors, and radiation therapy (RT)-that contribute to endothelial dysfunction and plaque instability. This scientific statement synthesizes the evidence on the interplay between cancer and coronary atherosclerosis, highlighting advances in noninvasive imaging modalities (ie, cardiac CT, nuclear imaging, cardiac magnetic resonance, echocardiography) for early detection, risk stratification, and surveillance of coronary artery disease in oncologic populations, and examines the role of invasive imaging techniques in guiding revascularization decisions. Given the elevated bleeding and thrombotic risks in these patients, individualized management of post-percutaneous coronary intervention medications and abbreviated dual antiplatelet therapy regimens is emphasized. This scientific statement also addresses knowledge gaps and reinforces the need for more evidence to improve risk stratification for atherosclerotic cardiovascular disease in patients with cancer. The shared pathobiology between coronary atherosclerosis and cancer necessitates an integrated, multidisciplinary approach to screening, diagnosis, and management.

Lower (<10 mm Hg) discharge echocardiographic mean gradients (MGs) following transcatheter aortic valve replacement with balloon-expandable valves are associated with lower ejection fraction and higher 5-year mortality compared with higher gradients. Using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, we studied the relationship between echocardiographic MG and patient prosthesis mismatch (PPM) following transcatheter aortic valve-in-valve replacement and clinical outcomes.

The Alterra Adaptive Prestent provides a landing zone for implantation of the 29 mm SAPIEN 3 transcatheter heart valve (THV) in patients with a dysfunctional right ventricular outflow tract (RVOT) to treat pulmonary regurgitation (PR). Here, we report 3-year outcomes from a pooled analysis of patients who underwent Alterra/SAPIEN 3 THV implantation enrolled in the ALTERRA pivotal trial, Continued Access Protocol, and Pulmonic Delivery System Registry.