Despite insufficient evidence to support direct-to-consumer genetic testing in routine clinical care, cardiovascular clinicians increasingly face questions about its utility and interpretation because individuals can purchase these tests directly from laboratories. A burgeoning marketplace offers an expanding array of testing options. In many cases, direct-to-consumer genetic testing advertises information that could inform one's risk of heritable disease, including insight into having a genetic predisposition to cardiovascular disease or data about gene-drug interactions that could affect response to cardiovascular medications. Navigating clinical questions about direct-to-consumer genetic testing involves understanding the evolution and oversight of the marketplace; the scope of direct-to-consumer genetic testing offerings; and the risks, benefits, and limitations of said testing. In this American Heart Association scientific statement, we summarize the state of the direct-to-consumer genetic testing industry, review types of cardiovascular genetic information that may be included in direct-to-consumer genetic testing, describe approaches to evaluate test quality, and provide resources for clinicians navigating questions about direct-to-consumer genetic testing. If direct-to-consumer genetic test information is used in clinical care, care should be taken to assess the limitations of the test, to contextualize the information specifically to the patient, and to corroborate potentially actionable monogenic findings.

Sex differences in the risk factors, diagnosis, treatment, and outcomes of patients with cardiovascular disease have been well described; however, the bulk of the literature has focused on heart disease in women. Data on sex differences in peripheral vascular disease are ill defined, and there is a need to report and understand those sex-related differences to mitigate adverse outcomes related to those disparities. Although peripheral vascular disease is a highly diverse group of disorders affecting the arteries, veins, and lymphatics, this scientific statement focuses on disorders affecting the peripheral arteries to include the aorta and its branch vessels. The purpose of this scientific statement is to report the current status of sex-based differences and disparities in peripheral vascular disease and to provide research priorities to achieve health equity for women with peripheral vascular disease.

Albuminuria-increased urine albumin excretion-is associated with cardiovascular mortality among patients with diabetes, hypertension, chronic kidney disease, or heart failure, as well as among adults with few cardiovascular risk factors. Many authors have hypothesized that albuminuria reflects widespread endothelial dysfunction, but additional work is needed to uncover whether albuminuria is directly pathologic or causative of cardiovascular disease. Urinary albumin-to-creatinine ratio is an attractive, unifying biomarker of cardiovascular, kidney, and metabolic conditions that may be useful for identifying and monitoring disease trajectory. However, albuminuria may develop through unique mechanisms across these distinct clinical phenotypes. This state-of-the-art review discusses the role of albuminuria in cardiovascular, kidney, and metabolic conditions; identifies potential pathways linking albuminuria to adverse outcomes; and provides practical approaches to screening and managing albuminuria for clinical cardiologists. Future research is needed to determine how broadly and how frequently to screen patients for albuminuria, whether it is cost-effective to treat low-grade albuminuria (10-30 mg/g), and how to equitably offer newer antiproteinuric therapies across the spectrum of cardiovascular-kidney-metabolic diseases.

Female patients are at greater risk of adverse events following non-ST-elevation acute coronary syndrome but less frequently receive guideline-recommended coronary angiography and revascularization. Routine invasive management benefits high-risk patients, but evidence informing the optimal timing of angiography specifically in female patients is lacking.

High out-of-pocket costs and financial toxicity related to heart failure treatment are substantial concerns. Two of 4 pillars of guideline-directed medical therapy for heart failure with reduced ejection fraction, for example, carry high costs that may attenuate their uptake. Furthermore, heart failure rarely occurs in isolation. Many patients have other comorbidities that require treatment, further driving up patients' out-of-pocket costs. Developing treatment plans that improve mortality without subjecting patients to financial toxicity can be challenging for several reasons. First, patients with heart failure can accrue out-of-pocket costs from multiple domains and can depend on a variety of insurance and pharmacy-related factors that can make determining patient-specific out-of-pocket cost estimates complicated. Second, strategies to mitigate financial toxicity involve health policy-level interventions and patient-level interventions. These have their own unique sets of challenges. Third, integrating out-of-pocket costs into shared decision-making requires nuanced and challenging discussions about whether a therapy is worth the cost. Though shared decision-making has been advocated, there are little data on how to best conduct these discussions. Health policies like the Inflation Reduction Act of 2022 may provide relief to some patients, and efforts to improve transparency have the potential to be beneficial. Over the long term, policy solutions such as value-based insurance design and patient engagement solutions that emphasize enhancing shared decision-making have important potential to yield durable results.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

Artificial intelligence is poised to transform cardio-oncology by enabling personalized care for patients with cancer, who are at a heightened risk of cardiovascular disease due to both the disease and its treatments. The rising prevalence of cancer and the availability of multiple new therapeutic options has resulted in improved survival among patients with cancer and has expanded the scope of cardio-oncology to not only short-term but also long-term cardiovascular risks resulting from both cancer and its treatments. However, there is considerable heterogeneity in cardiovascular risk, driven by the nature of the malignancy as well as each individual's unique characteristics. The use of novel therapies, such as targeted therapies and immune checkpoint inhibitors, across multiple cancer groups has also broadened the populations among which cardiotoxicity has become an important consideration of therapy. Therefore, the ability to understand and personalize cardiovascular risk management in patients with cancer is a key target for artificial intelligence, which can deduce and respond to complex patterns within the data. These advances necessitate an overview of established biomarkers of risk, spanning advanced imaging, diagnostic testing, and multi-omics, the evidence supporting their use, and the proven and proposed role of artificial intelligence in refining this risk to attain greater precision in risk prediction and management in cardio-oncologic care.

Larry A. Allen, MD, MHS, FAHA, FACC; Mats Börjesson, MD, PhD, FACC; Alan C. Braverman, MD, FACC; Julie A. Brothers, MD; Silvia Castelletti, MD, MSc, FESC; Eugene H. Chung, MD, MPH, FHRS, FAHA, FACC; Timothy W. Churchill, MD, FACC; Guido Claessen, MD, PhD; Flavio D'Ascenzi, MD, PhD; Douglas Darden, MD; Peter N. Dean, MD, FACC; Neal W. Dickert, MD, PhD, FACC; Jonathan A. Drezner, MD; Katherine E. Economy, MD, MPH; Thijs M.H. Eijsvogels, PhD; Michael S. Emery, MD, MS, FACC; Susan P. Etheridge, MD, FHRS, FAHA, FACC; Sabiha Gati, BSc (Hons), MBBS, PhD, MRCP, FESC; Belinda Gray, BSc (Med), MBBS, PhD; Martin Halle, MD; Kimberly G. Harmon, MD; Jeffrey J. Hsu, MD, PhD, FAHA, FACC; Richard J. Kovacs, MD, FAHA, MACC; Sheela Krishnan, MD, FACC; Mark S. Link, MD, FHRS, FAHA, FACC; Martin Maron, MD; Silvana Molossi, MD, PhD, FACC; Antonio Pelliccia, MD; Jack C. Salerno, MD, FACC, FHRS; Ankit B. Shah, MD, MPH, FACC; Sanjay Sharma, BSc (Hons), MBChB, MRCP (UK), MD; Tamanna K. Singh, MD, FACC; Katie M. Stewart, NP, MS; Paul D. Thompson, MD, FAHA, FACC; Meagan M. Wasfy, MD, MPH, FACC; Matthias Wilhelm, MD.

Groundbreaking achievements in science and medicine have contributed to reductions in cardiovascular disease and stroke mortality over the past 7 decades. Many of these advances were supported through investments by the National Institutes of Health, the global leader in funding biomedical research. This public investment has produced important economic returns, including supporting >400 000 jobs and roughly $93 billion in economic activity in the United States. Unfortunately, public funding has not kept pace with the burden of disease or rates of inflation. As the nation's oldest and largest volunteer organization dedicated to fighting heart disease and stroke, research is critical to the American Heart Association's mission. Given the American Heart Association's unique position in representation of patients, clinicians, and scientists and as a research funder, we offer the following principles to optimize the future of the US biomedical research enterprise in general and the National Institutes of Health in particular. Specifically, the United States should continue to prioritize innovative and impactful research; to improve efficiency and transparency in its peer review process; to lead in translating evidence into practice; to support the current and future biomedical workforce; and to ensure robust and reliable public investment for the future. The American Heart Association reiterates our strong support for the National Institutes of Health and federal agencies that fund and implement biomedical and population-based research initiatives, which yield important economic returns. These agencies are vital to support today's current and future health challenges, to drive foundational science, to improve patient health, to reduce the global disease burden, to address upstream and preventive strategies, and to improve the value of our public health and health care investments.

Pathogenic/likely pathogenic (LP) desmin (DES) variants cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease, sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, left ventricular assist device/cardiac transplant, HF-related death) in patients with pathogenic/LP DES variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with pathogenic/LP DES variants through a systematic review and individual patient data meta-analysis using published reports.

Cardiac amyloidosis is an underdiagnosed cause of infiltrative cardiomyopathy, leading to heart failure across the spectrum of ejection fractions. Although there are approved disease-modulating therapies for the transthyretin subtype (transthyretin amyloid cardiomyopathy [ATTR-CM]), the role of heart failure medications remains uncertain and challenging in clinical practice. Their effects on clinical outcomes, such as mortality and hospitalization, are unknown for ATTR-CM. This review aims to explore the use of these medications in ATTR-CM, considering the disease's stage and patient-specific issues, such as fluid homeostasis, autonomic dysfunction, conduction disorders, low and fixed stroke volumes, and decreased functional capacity. As our understanding of this condition deepens, it is important to reassess the impact of contemporary heart failure medication in ATTR-CM. Finally, the relevance of guideline recommendations for heart failure drugs based on left ventricular ejection fraction should be reconsidered in the context of ATTR-CM.

The heart is a highly sex-biased organ, as sex shapes innumerable aspects of heart health and disease. Sex chromosomes and sex hormones -testosterone, progesterone, and estrogen- establish and perpetuate the division between male and female myocardium. Of these differentiating factors, the insulating effects of estrogen have been rigorously interrogated and reviewed, whereas the influence of sex chromosomes, testosterone, and progesterone remains in dispute or ill-defined. Here, we synthesize growing evidence that sex chromosomes and sex hormones substantially bias heart form, function, and dysfunction in a context-dependent fashion. The discrete protective functions ascribed to each of the 3 estrogen receptors are also enumerated. Subsequently, we overview obstacles that have historically discouraged the inclusion of female subjects in basic science such as the impact of the female estrus cycle and reproductive senescence on data reliability and reproducibility. Furthermore, we weigh the utility of several common strategies to intercept and rescue sex-specific protection. Last, we warn of common compounds in animal chow and cell culture that interfere with estrogen signaling. In sum, we survey the controversies and challenges that stem from sex-inclusive cardiovascular research, comparing the possible causes of cardiac sex bias, elucidating sex chromosome or hormone-dependent processes in the heart, describing common lapses that imperil female and male cell and animal work, and illuminating facets of the female heart yet unexplored or still uncertain.

Hypertension in pregnancy contributes substantially to maternal morbidity and mortality, persistent hypertension, and rehospitalization. Hypertensive disorders of pregnancy are also associated with a heightened risk of cardiovascular disease, and timely recognition and modification of associated risk factors is crucial in optimizing long-term maternal health. During pregnancy, there are expected physiologic alterations in blood pressure (BP); however, pathophysiologic alterations may also occur, leading to preeclampsia and gestational hypertension. The diagnosis and effective management of hypertension during pregnancy is essential to mitigate maternal risks, such as acute kidney injury, stroke, and heart failure, while balancing potential fetal risks, such as growth restriction and preterm birth due to altered uteroplacental perfusion. In the postpartum period, innovative and multidisciplinary care solutions that include postpartum maternal health clinics can help optimize short- and long-term care through enhanced BP management, screening of cardiovascular risk factors, and discussion of lifestyle modifications for cardiovascular disease prevention. As an adjunct to or distinct from postpartum clinics, home BP monitoring programs have been shown to improve BP ascertainment across diverse populations and to lower BP in the months after delivery. Because of concerns about pregnant patients being a vulnerable population for research, there is little evidence from trials examining the diagnosis and treatment of hypertension in pregnant and postpartum individuals. As a result, national and international guidelines differ in their recommendations, and more studies are needed to bolster future guidelines and establish best practices to achieve optimal cardiovascular health during and after pregnancy. Future research should focus on refining treatment thresholds and optimal BP range peripartum and postpartum and evaluating interventions to improve postpartum and long-term maternal cardiovascular outcomes that would advance evidence-based care and improve outcomes worldwide for people with hypertensive disorders of pregnancy.

Globally significant variation in treatment and course of heart valve disease (HVD) exists, and outcome measurement is procedure focused instead of patient focused. This article describes the development of a patient-related (International Consortium for Health Outcomes Measurement) standard set of outcomes and case mix to be measured in patients with HVD.

Chest radiotherapy (XRT) plays a crucial role in the treatment of a multitude of cancers including breast, lung, esophageal, and lymphoma. Although XRT enhances cancer survival rates, it may also expose healthy bystander tissues to radiation, potentially leading to severe complications. Initially considered relatively resistant to radiation damage, the heart has been shown over the past 4 decades to be susceptible to radiation-induced cardiovascular toxicity and despite advances in XRT which can minimize radiation exposure to heart tissue, no cardiac radiation dose is entirely safe. The clinical spectrum of radiation-induced cardiovascular toxicity is broad, encompassing coronary artery disease, myocardial dysfunction, valvular abnormalities, and pericardial disorders. Radiation-induced cardiovascular toxicity may manifest acutely or many years after XRT, with each condition more likely to present at certain time points post-XRT. Cardiac imaging is a crucial tool in both the screening and diagnosis of radiation-induced cardiovascular toxicity with an understanding of its pathophysiology, incidence, and progression required to implement a comprehensive, multimodality imaging approach to detect and manage these complications effectively.

Critical care cardiology refers to the practice focus of and subspecialty training for the comprehensive management of life-threatening cardiovascular diseases and comorbid conditions that require advanced critical care in an intensive care unit. The development of coronary care units is often credited for a dramatic decline in mortality rates after acute myocardial infarction throughout the 1960s. As the underlying patient population became progressively sicker, changes in organizational structure, staffing, care delivery, and training paradigms lagged. The coronary care unit gradually evolved from a focus on rapid resuscitation from ventricular arrhythmias in acute myocardial infarction into a comprehensive cardiac intensive care unit designed to care for the sickest patients with cardiovascular disease. Over the past decade, the cardiac intensive care unit has continued to transform with an aging population, increased clinical acuity, burgeoning cardiac and noncardiac comorbidities, technologic advances in cardiovascular interventions, and increased use of temporary mechanical circulatory support devices. Herein, we provide an update and contemporary expert perspective on the organizational structure, staffing, and care delivery in the cardiac intensive care unit; examine the challenges and opportunities present in the education and training of the next generation of physicians for critical care cardiology; and explore quality improvement initiatives and scientific investigation, including multicenter registry initiatives and randomized clinical trials, that may change clinical practice, care delivery, and the research landscape in this rapidly evolving discipline.

Atherosclerotic cardiovascular disease is a major health concern worldwide and requires effective preventive measures. Lp(a) (lipoprotein [a]) has recently garnered attention as an independent risk factor for astherosclerotic cardiovascular disease, with proinflammatory and prothrombotic mechanisms contributing to its atherogenicity. On an equimolar basis, Lp(a) is ~5 to 6 times more atherogenic than particles that have been widely associated with adverse cardiovascular outcomes, such as LDL (low-density lipoprotein). Lp(a) can enter the vessel wall, leading to the accumulation of oxidized phospholipids in the arterial intima, which are crucial for initiating plaque inflammation and triggering vascular disease progression. In addition, Lp(a) may cause atherothrombosis through interactions between apoA (apolipoprotein A) and the platelet PAR-1 (protease-activated receptor 1) receptor, as well as competitive inhibition of plasminogen. Because Lp(a) is mostly determined on genetic bases, a 1-time assessment in a lifetime can suffice to identify patients with elevated levels. Mendelian randomization studies and post hoc analyses of randomized trials of LDL cholesterol-lowering drugs showed a causal link between Lp(a) concentrations and cardiovascular outcomes, with therapeutic reduction of Lp(a) expected to contribute to estimated cardiovascular risk mitigation. Many Lp(a)-lowering drugs, including monoclonal antibodies, small interfering ribonucleic acids, antisense oligonucleotides, small molecules, and gene editing compounds, are at different stages of clinical investigation and show promise for clinical use. In particular, increased Lp(a) testing and treatment are expected to have a substantial impact at the population level, enabling the identification of high-risk individuals and the subsequent prevention of a large number of cardiovascular events. Ongoing phase 3 trials will further elucidate the cardiovascular benefits of Lp(a) reduction over the long term, offering potential avenues for targeted interventions and improved cardiovascular outcomes.

Hypertrophic cardiomyopathy is a common but underrecognized cardiac disorder characterized by a heterogenous phenotype that includes increased left ventricular thickness, outflow obstruction, diastolic dysfunction, and arrhythmia. Hypertrophic cardiomyopathy is often heritable and associated with pathogenic variants in sarcomeric genes. While not curable, an integrated approach involving medical, interventional, and surgical care can have a considerable impact on disease burden, quality of life, and mortality. This review provides a practical overview of important topics in hypertrophic cardiomyopathy, including evaluation of differential diagnosis, imaging, provocation of left ventricular outflow obstruction, treatment of obstructive and nonobstructive hypertrophic cardiomyopathy with negative inotropic therapy and myosin inhibition, as well as surgical and interventional approaches to septal reduction and mitral valve intervention.

Peripheral artery disease (PAD) is an atherosclerotic condition that affects a growing number of individuals worldwide, with estimates exceeding 220 million. One of the central hallmarks of PAD is lower extremity pain, which may present as intermittent claudication and atypical leg pain, and, in more severe cases, ischemic rest pain, neuropathic pain, or phantom limb pain in those who underwent amputation. Although the majority of individuals with PAD may experience pain that is chronic in nature, the pathogenesis and phenomenology of pain may differ. Nociceptive, inflammatory, and neuropathic mechanisms all play a role in the generation of pain. Pain in PAD results in severe disability and can copresent with distress, sickness behaviors such as avoidance and further deconditioning, and concomitant depression, anxiety, and addiction secondary to opioid use. These factors potentially lead to chronic pain interacting with a multitude of domains of functioning, including physical, emotional, and behavioral. Whereas pain is a normal adaptive response, self-defeating behaviors and cognitions contribute to the persistence or worsening of the chronic pain experience, disability, and distress. Much remains unknown about the phenomenology of pain in PAD and its clinical subgroups and how it affects outcomes. Borrowing from other chronic pain syndromes, multimodal pain management strategies that emphasize a biopsychosocial model have generated a solid evidence base for the use of cognitive behavioral approaches to manage pain. Multimodal pain management in PAD is not the norm, but theoretical pathways and road maps for further research, assessment, and clinical implementation are presented in this scientific statement.