Invasive epicardial coronary physiologic assessment is increasingly performed to evaluate the hemodynamic significance of intermediate coronary lesions and is recommended by guideline committees. Whereas much of the practice in coronary physiologic assessment is based on evidence, some non-evidence-based traditions and misconceptions persist. The aim of this review is to highlight evidence-based practice in invasive epicardial coronary physiologic assessment and to refute or validate common elements of clinical practice.

The United States is facing a demographic shift as the population of older adults grows rapidly, with the proportion of Americans ≥65 years of age projected to double by 2060. This aging trend will have far-reaching effects on health care systems, especially because aging is a primary risk factor for cardiovascular disease. Age-related cardiovascular changes, such as increased arterial stiffness, endothelial dysfunction, and reduced elasticity, increase the risk for hypertension, atherosclerosis, and other risk factors. Older adults often experience additional complications, including obesity, diabetes, and metabolic diseases, further increasing their cardiovascular risk. Every year, >720 000 Americans experience myocardial infarction or coronary artery disease-related deaths, with older adults disproportionately affected. Individuals ≥75 years of age account for 30% to 40% of all acute coronary syndrome hospitalizations, often presenting with complex coronary disease and associated geriatric syndromes, such as frailty, cognitive impairment, and multimorbidity, complicating revascularization strategies. American College of Cardiology/American Heart Association guidelines for coronary revascularization primarily focus on younger populations, leaving substantial gaps for older adults with geriatric complexities. This scientific statement highlights the need for individualized approaches that consider geriatric syndromes, patient preferences, cognitive function, and life expectancy. This scientific statement outlines key aims: to review age-related cardiovascular changes and geriatric syndromes, provide pragmatic revascularization strategies, and advocate for shared decision-making. Addressing these knowledge gaps is essential for optimizing cardiovascular care for older adults, ensuring that treatment aligns with patient goals and accounts for the unique risks they face.

Missing data in clinical trials remains an ongoing concern. With the expansion of data privacy efforts and the consequent inability to contact trial participants for follow-up, the magnitude and reasons of missing data in clinical trials have shifted. The impact of missing data on a clinical trial results largely depends on the reason why the data are missing. When data are missing at random, the influence on the study's conclusions may be minimal. In contrast, when data are missing not at random, the integrity of the trial results can be compromised. For example, if participants are lost to follow-up or withdraw consent due to adverse reactions or side effects like bleeding, then the remaining participants may disproportionately represent those who can tolerate the therapy or are less frail, leading to biased conclusions regarding the drug's safety and efficacy, a phenomenon referred to as differential censoring. The best strategy is to minimize missing data from the outset of the trial, which includes designing an informed consent form that sets the expectation that and the alternate methods by which outcomes will be tracked even if the participant elects to discontinue study treatment. Likewise, rather than waiting until the end of the study, missing data should be continually and proactively minimized during the trial by offering patients more convenient and infrequent visit strategies or follow-up through relatives or other health care professionals as needed. Also, it is critical to characterize the basis for data missingness so that its impact on trial interpretation can be better assessed. This article provides a roadmap to successfully implement all of these strategies to minimize missing data.

The rapid advancement of genomic and precision medicine has expanded the role of genetics and genomics in the diagnosis, risk stratification, and management of cardiovascular diseases. With the decreasing cost and increasing accessibility of genetic testing, its clinical utility continues to expand, necessitating updated policies to ensure equitable access, appropriate regulatory oversight, and ethical data stewardship. This policy statement by the American Heart Association provides a framework addressing key policy areas, including equitable implementation of genetic testing, the impact of federal regulations, data privacy concerns, reimbursement for genetic counseling services, and the integration of emerging technologies such as artificial intelligence in cardiovascular genomics into clinical practice. This policy statement underscores the importance of strategic investments in biobanking and genomic research across all populations to enhance variant interpretation and to improve risk prediction models. In addition, it highlights the evolving landscape of pharmacogenomics, polygenic risk scores, and precision public health approaches to cardiovascular disease prevention. By advocating for a multidisciplinary approach that bridges scientific innovation, clinical application, and policy development, this policy statement aims to optimize the benefits of genetic and genomic testing while mitigating disparities and ethical challenges in its implementation.

Pathogenic variants in ALPK3 (α-protein kinase 3), an atypical α‑kinase acting as a sarcomeric M-band scaffold, cause cardiomyopathy with severity linked to zygosity. We present a comprehensive review with systematic curation of peer-reviewed clinical and experimental reports through June 9, 2025, encompassing 156 patient-level variants and all published preclinical models. Biallelic loss-of-function variants lead to severe, often lethal cardiomyopathy with prenatal or early onset presentation and extracardiac involvement. Heterozygous protein-truncating variants, defined as nonsense or frameshift (resulting from insertion/deletion events or splicing mutations), explain ≈1% to 4% of adult hypertrophic cardiomyopathy, often with apical/septal hypertrophy, right ventricular involvement, fibrosis, and risk of progression. ALPK3 lacks catalytic activity and maintains sarcomeric proteostasis by scaffolding MYOMs (myomesins), MuRF (muscle ring-finger protein) E3 ligases, and SQSTM1 (sequestosome-1)/p62. Loss of this scaffolding function displaces MYOMs, drives thick‑filament protein aggregation, and precipitates severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes and multiple mouse models. Therapeutic proof‑of‑concept has now been achieved on 2 fronts: (1) pharmacological correction of sarcomeric hypercontractility with the myosin inhibitor mavacamten and (2) durable phenotypic rescue in global knockout mice using an adeno-associated virus-delivered miniALPK3 gene‑replacement construct. Together, these data position ALPK3 cardiomyopathy as a compelling target for precision medicine. Early genetic diagnosis, genotype-tailored surveillance, and focused development of gene-replacement or editing strategies, potentially combined with modulators of the ALPK3-MuRF proteostatic axis, offer a realistic path to disease-modifying therapy for this once enigmatic condition.

The rapid development and integration of artificial intelligence (AI), including predictive, generative, and emerging agentic tools, into cardiovascular and stroke care is outpacing traditional evaluation frameworks and the generation of robust clinical evidence. This science advisory addresses the urgent need for pragmatic, risk-proportionate approaches to the evaluation and monitoring of health care AI. AI implementation practices often rely on real-world or anecdotal evidence, with considerable variability in local validation, bias assessment, and postdeployment monitoring. Several evaluation frameworks exist, but they can be difficult to operationalize, especially outside of well-resourced health systems. We propose and discuss evaluation across 3 phases: predeployment, implementation, and postdeployment. We also provide 4 pragmatic guiding principles for health systems that are beginning to set up AI governance processes, including strategic alignment, ethical evaluation, usefulness and effectiveness evaluation, and financial performance, to inform health system selection, validation, deployment, and actionable monitoring of AI tools. The American Heart Association's extensive hospital and volunteer network and commitment to evidence-based practice position it as a trusted leader in advancing responsible AI governance. By grounding evaluation and monitoring in these principles, this science advisory aims to ensure that AI adoption in health care is safe, effective, equitable, and sustainable, ultimately improving patient outcomes and supporting high-quality AI-enabled care.

Risk stratification of patients with chest pain has traditionally focused on identifying obstructive coronary artery disease (CAD). Using this traditional approach, many symptomatic individuals are found to have nonobstructive CAD. The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance chest pain guideline widened the scope of cardiac computed coronary angiography, resulting in increased identification of patients with nonobstructive CAD. In addition, recent advances in artificial intelligence solutions, hardware, and software have allowed identification of microvascular disease and introduced new risk categories within nonobstructive CAD with a risk continuum between primary and secondary prevention. There is thus a growing need for care teams to remain current on the diagnosis, risk stratification, and management of patients with nonobstructive CAD. Whereas only a subset of patients with chest pain are found to have true angina despite nonobstructive CAD, underlying nonobstructive CAD warrants attention. Medical management of nonobstructive CAD plays an essential role in plaque stabilization and regression to decrease the risk of acute coronary syndromes. New pharmacologic therapies and noninvasive plaque evaluation raise the potential for plaque-driven medical interventions. However, data in patients with chest pain who are found to have nonobstructive CAD are limited, and, in clinical practice, multiple factors lead to missed opportunities for precision therapies, with proven disparities in care. We review the current evidence on risk stratification for nonobstructive CAD and discuss its implications and medical management options.

Calmodulinopathies are very rare genetic disorders associated with a high risk for sudden cardiac death. Disease-causing variants in 1 of the 3 identical CALM genes cause severe forms of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or idiopathic ventricular fibrillation, and there are many open questions concerning management and underlying mechanisms. What is currently known depends largely on the initial publications from the International Calmodulinopathy Registry. However, progress is delayed because the accrual of patients in the International Calmodulinopathy Registry is slow. As we did long ago for long QT syndrome, this is a call for action, requesting doctors all over the world to enroll even their isolated cases in the registry. This is the only way to obtain, for an adequate number of patients, the data necessary to define the spectrum of clinical manifestations and the genotype-phenotype correlation essential for an improved risk stratification and best therapeutic management. If you are willing to contribute, please contact us.

Multifocal ectopic Purkinje-related premature contractions syndrome presents as a rare cardiac disorder characterized by frequent multifocal ectopic ventricular beats with narrow QRS complexes, originating from various ectopic foci along the fascicular-Purkinje system. It is characterized by mutations in the SCN5A gene, inducing a gain-of-function in the human cardiac voltage-gated Na+ channel (Nav1.5), which causes an alteration in the action potentials of the cardiomyocytes. The syndrome was initially delineated in 2012 by Laurent et al in 3 Dutch families, subsequently garnering recognition through several reported cases worldwide. Clinically, it often manifests with a familial predisposition to other arrhythmogenic cardiac diseases, alongside symptoms such as palpitations and syncope. A key diagnostic hallmark is the high daily burden of multifocal premature ventricular contractions observed on 24-hour dynamic ECG, with evidence of repetitive ventricular arrhythmias. This can potentially induce a reversible form of left ventricular dilation with systolic dysfunction, known as premature ventricular contraction-induced cardiomyopathy. Diagnosis may be challenging, requiring exclusion of the most frequent causes of ventricular arrhythmias first. The disappearance of arrhythmias during a stress test and the inefficacy of catheter ablation procedures may serve as additional elements to bolster the suspicion of multifocal ectopic Purkinje-related premature contractions syndrome. Genetic testing and electrophysiological studies are pivotal in confirming the diagnosis. Therapeutic management of this syndrome primarily involves medical therapy with class I antiarrhythmic drugs, such as flecainide and quinidine, which may reduce ventricular arrhythmias and associated symptoms. In this systematic review, our aim was to provide an exhaustive insight into the genetic basis, diagnosis, and treatment strategies for this intriguing yet relatively underexplored syndrome.

Cardiovascular and metabolic health are influenced by the circadian system, which regulates 24-hour rhythms across numerous physiologic processes. Disruptions to circadian rhythmicity can adversely affect cardiometabolic function and health. Given the importance of circadian health to overall human health, this scientific statement provides an overview of the circadian system and key behavioral factors that can synchronize or desynchronize these rhythms, including light exposure, food intake, physical exercise, and sleep timing. We also summarize the literature on associations between circadian health and cardiometabolic health indicators, such as excessive weight, type 2 diabetes (T2D), hypertension, and cardiovascular disease. We discuss strategies to improve circadian health and reduce circadian disruptions, focusing on interventions that target the key synchronizers of circadian rhythms and involve appropriate timing of exposure to these synchronizers. These include morning bright light exposure and avoidance of light at night, as well as appropriately timed sleep, meals, and exercise. Clinicians, researchers, policymakers, and the public should recognize the role of circadian rhythms in maintaining and promoting cardiometabolic health and focus on identifying modifiable behaviors that can improve them.

Developed by the American Heart Association, these Guidelines represent the first comprehensive update of education recommendations since 2020. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these are guidelines for the design and delivery of resuscitation training for health care professionals and lay rescuers. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include the use of cardiopulmonary resuscitation feedback devices in training, rapid-cycle deliberate practice, teamwork and leadership training, manikin fidelity, gamified learning, virtual and augmented reality, use of cognitive aids, stepwise training, blended learning, scripted debriefing, instructor training, alternative objects for lay rescuer chest compression training, and special considerations for training in the management of opioid overdose. How certain personal considerations may influence the overall impact of education are also reviewed, including disparities accordingly related to gender, race, socioeconomic status, and language; the impact of training for school children; and factors that act as barriers or facilitators to lay rescuer willingness to perform cardiopulmonary resuscitation. We conclude with a summary of current knowledge gaps in resuscitation education science and a discussion of future directions for optimizing the impact of resuscitation training programs.

Cardiac arrest is common and deadly, affecting up to 700 000 people in the United States annually. Advanced cardiac life support measures are commonly employed to improve outcomes. This 2025 guideline on adult post-cardiac arrest care from the American Heart Association summarizes the most recent published evidence for and recommendations on several important areas of post-cardiac arrest management. Based on structured evidence reviews, guidelines are provided for initial blood pressure, oxygen, ventilation, and glucose goals. Evidence evaluating the routine use of antibiotics after return of spontaneous circulation is reviewed. The update also reviews diagnostic testing modalities, temperature control goals and duration, and the use of percutaneous coronary intervention and mechanical circulatory support in the patient resuscitated from cardiac arrest. New data regarding the detection and management of seizures have been incorporated, along with updates regarding the timing and modalities used in neuroprognostication. These guidelines now differentiate prognostication for favorable versus unfavorable outcome. New sections on the utility of advanced neuromonitoring, along with definitions and treatment options for myoclonus, are included to guide the clinician. Expanded recommendations regarding how to optimize survivorship for patients, caregivers, and rescuers are reviewed. Finally, the potential role of organ donation in the patient resuscitated from cardiac arrest is reviewed.

This executive summary provides an overview of the 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, which is organized around the Utstein Formula for Survival and provides updated recommendations aimed at improving survival rates and neurological outcomes following cardiac arrest. This executive summary outlines key changes, emphasizing the importance of high-quality chest compressions, early defibrillation, and the integration of advanced resuscitation techniques. These Guidelines also highlight critical post-cardiac arrest care strategies, including targeted temperature management and hemodynamic stabilization. Additionally, they stress the need for population-specific resuscitation approaches, particularly for pediatric patients, pregnant individuals, and individuals with cardiac arrest due to special circumstances. A strong focus is placed on continuous training and education for both medical professionals and lay rescuers to enhance the implementation and effectiveness of these lifesaving interventions. The 2025 Guidelines also highlight the importance of an integrated system of people, protocols, policies, and resources to achieve quality improvement in cardiac arrest care. An overview of ethical considerations relevant to emergency cardiovascular care, resuscitation, and approaches to decision-making surrounding cardiac arrest is also included. By following these updated recommendations, the American Heart Association seeks to optimize resuscitation efforts and improve patient outcomes in cardiac emergencies.

The 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care is based on the extensive evidence evaluation performed in conjunction with the International Liaison Committee on Resuscitation. The Adult Basic and Advanced Life Support, Pediatric Basic and Advanced Life Support, Neonatal Resuscitation, Resuscitation Education Science, Special Circumstances, Post-Cardiac Arrest Care, Ethics, and Systems of Care Writing Groups drafted, reviewed, and approved recommendations, assigning to each recommendation a Class of Recommendation (ie, strength) and Level of Evidence (ie, quality). The 2025 Guidelines are organized in knowledge chunks that are grouped into discrete modules of information on specific topics or management issues. Each chapter of the 2025 Guidelines underwent blinded peer review by subject matter experts and was also reviewed and approved for publication by the American Heart Association Science Advisory and Coordinating Committee and the American Heart Association Executive Committee. Chapters with pediatric content (Neonatal Resuscitation, Pediatric Basic and Advanced Life Support) were also co-led by the American Academy of Pediatrics, and thereby the content was reviewed and approved by the American Academy of Pediatrics Board of Directors. The American Heart Association has rigorous conflict of interest policies and procedures to minimize the risk of bias or improper influence during development of the guidelines. Anyone involved in any part of the guideline development process disclosed all commercial relationships and other potential conflicts of interest.

Codeveloped by the American Heart Association and the American Academy of Pediatrics, this publication presents the 2025 guidelines for basic life support during cardiopulmonary resuscitation and emergency cardiovascular care of the pediatric patient, excluding the newborn infant, and represents the first comprehensive update of treatment recommendations since 2020. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines are for lay rescuers and health care professionals with recommendations designed to improve survival from sudden cardiac arrest and acute life-threatening cardiopulmonary problems. Existing guidelines remain relevant unless specifically updated in this publication. Topics reviewed include the initiation of cardiopulmonary resuscitation; pulse check; components of high-quality cardiopulmonary resuscitation; chest compression technique; support surfaces for cardiopulmonary resuscitation; opening the airway; coordination of shock and cardiopulmonary resuscitation; types of defibrillators or automated external defibrillators; defibrillator paddle or pad size, type, position; treatment of inadequate breathing with a pulse; and foreign-body airway obstruction. Key topics that are new, are substantially revised, or have significant new literature include the elimination of 2-finger chest compressions in infants due to ineffectiveness of achieving proper depth with a recommendation of 1-hand or 2 thumb-encircling hands technique; the immediate application and use of an automated external defibrillator with a pediatric attenuator if available for cardiac arrest; and in infants with severe foreign-body airway obstruction repeated cycles of 5 back blows alternating with 5 chest thrusts (no abdominal thrusts), and in children with severe foreign-body airway obstruction repeated cycles of 5 back blows alternating with 5 abdominal thrusts.

In this chapter, the American Heart Association provides guidance on ethical considerations relevant to cardiopulmonary resuscitation and emergency cardiovascular care. An overview is provided of ethical frameworks that provide a structure through which difficult decisions can be analyzed. These include principlism, currently the predominant medical ethical framework, which considers moral principles of beneficence, nonmaleficence, respect for autonomy, and justice. Additional consideration is given to the value of dignity, and other ethical frameworks such as narrative ethics, crisis standards of care, utilitarianism, virtue ethics, and deontology. The importance of equity and the imperative for health care professionals and their organizations to actively address structural inequities, social determinants of health and resulting disparities related to Emergency Cardiovascular Care is highlighted. Processes for decision-making are discussed, including guidance on advance directives and shared decision-making. Decisions to initiate or withhold and subsequently to continue or terminate resuscitation are reviewed at length. In addition to considering this decision in adults and geriatric patients, specific attention is given to decision-making in children, newborn infants, and pregnant patients. The impact of prognostic uncertainty on these decisions is discussed, as well as the evaluation of potentially ineffective therapies and cultural and religious considerations. Other ethical topics are addressed briefly, including processes for research and knowledge generation; the impact of resuscitation on health care professionals, survivors, laypersons, families, and caregivers; family presence during resuscitation; crisis standards of care; advanced therapies, including extracorporeal support; and organ and tissue donation.

The American Heart Association's 2025 Adult Basic Life Support Guidelines build upon prior versions with updated recommendations for assessment and management of persons with cardiac arrest, as well as respiratory arrest and foreign-body airway obstruction. The chapter addresses the important elements of adult basic life support including initial recognition of cardiac arrest, activation of emergency response, provision of high-quality cardiopulmonary resuscitation, and use of an automated external defibrillator. In addition, there are updated recommendations on the treatment of foreign-body airway obstruction. The use of opioid antagonists (eg, naloxone) during respiratory or cardiac arrest is incorporated into the adult basic life support algorithms, with more detailed information provided in "Part 10: Adult and Pediatric Special Circumstances of Resuscitation."

The guidelines in this document from the American Heart Association and the American Academy of Pediatrics focus upon optimal care of the newborn infant, including those who are proceeding to a normal transition from the fluid-filled uterine environment to birth. Newborn infants who are proceeding to normal transition can benefit from deferred cord clamping for at least 60 seconds in most instances, skin-to-skin with their parent soon after birth, and appropriate assistance with thermoregulation. Some newborn infants require assistance during transition, with interventions ranging from warming and tactile stimulation to advanced airway management, assisted ventilation, oxygen therapy, intravascular access, epinephrine, and volume expansion. In this context, individuals, teams, and health care settings that care for newborn infants should be prepared and have access to appropriate training and resources for neonatal resuscitation. The newborn chain of care provides guidance on considerations that may lead to optimal outcomes for newborn infants starting from prenatal care to recovery and follow-up.

Improving survival and quality of life after cardiac arrest requires integrated systems of people, protocols, policies, and resources along with ongoing data acquisition and review. Such systems of care, which are highly influenced by the environment in which they operate, produce efficiency and effectiveness in responding to cardiac arrest. Part 4 of the 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care focuses on systems of care, emphasizing elements that are relevant to a broad range of resuscitation situations. The chapter follows the Chain of Survival, beginning with prevention and preparedness to resuscitate, proceeding to early identification of cardiac arrest, and moving to effective resuscitation through to post-cardiac arrest care, survivorship, and recovery. This Part provides cardiac arrest systems of care guidelines on how to train specific personnel, protocols that have been demonstrated to be effective, as well as the incorporation of nonhuman resources to optimize cardiac arrest care with ongoing debriefing and quality improvement strategies. Specific to out-of-hospital cardiac arrest, included are recommendations about emergency medical services team composition and transport recommendations, community initiatives to promote lay rescuer response, public access defibrillation and naloxone, and an enhanced role for emergency telecommunicators. Germane to in-hospital cardiac arrest are recommendations about cardiac arrest prevention and code team composition. Specific recommendations about extracorporeal membrane oxygenation cardiopulmonary resuscitation, transport to specialized cardiac arrest centers, organ donation, survivorship systems, and performance measurement across the continuum of resuscitation situations are also included.