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.

Representativeness in randomized clinical trials remains a critical concern, affecting the external validity of trial results, equitable access to the risks and benefits of research participation, and public trust in clinical research. Although representative participation by members of groups traditionally underrepresented in clinical trials is just a surrogate for true diversity, equity, inclusion, and belonging in clinical trials, it can be quantified, allowing stakeholders to add empirical rigor to diversity, equity, inclusion, and belonging efforts. Multiple ways to measure representativeness have been proposed, including the participation-to-prevalence ratio, raw participation proportions or numbers for relevant subgroups, and enrollment fraction for relevant subgroups. These methods have strengths and weaknesses and may be appropriate to report in certain circumstances, depending on why stakeholders seek to assess representativeness. Stakeholders-including regulatory agencies, journal editors, clinical trial investigators, and trial sponsors-may use quantitative measures of representativeness to establish trial enrollment standards, monitor equitable participation in ongoing trials, and condition funding or drug or device approval on achieving specific representativeness targets. However, using quantitative measures of representativeness in this way could have unintended consequences, including researchers "gaming" recruitment strategies to meet target numbers, overlooking nuanced variations within communities, and potentially incentivizing problematic and exploitative recruitment strategies. Although no single method of measuring representativeness offers a comprehensive solution for increasing diversity, equity, inclusion, and belonging in all randomized clinical trials, a carefully designed, multifaceted approach to measuring representativeness may provide stakeholders with useful perspectives for measuring progress in increasing the diversity of clinical trial participation. For stakeholders seeking a single number to assess the representativeness of a trial enrolling patients with a disease state with well-delineated demographics, the participation-to-prevalence ratio is ideal; however, for a more nuanced view of representativeness, the combination of enrollment fraction in subgroups of relevance plus a full report of the demographics of patients approached for enrollment may be more appropriate.

Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation.

Despite advancements in diagnostics and therapeutics for cardiovascular disease, significant health disparities persist among patients from historically marginalized racial and ethnic groups, women, individuals who are socioeconomically under-resourced or underinsured, and those living in rural communities. While transcatheter interventions have revolutionized the treatment landscape in cardiology, populations bearing the greatest burden of disease continue to face inequitable access and poorer outcomes. A notable gap in the literature concerns the role of modern approaches to cardiovascular device innovation in shaping and perpetuating health disparities. Health equity has been declared one of the top strategic initiatives for 2022 to 2025 by the Food and Drug Administration Center for Devices and Radiological Health, underscoring the need for greater attention, dialogue, and targeted interventions in this space. This narrative review uses the cardiovascular device life cycle as a conceptual framework to enhance understanding and guide future efforts to mitigate disparities in the field of interventional cardiology. Drawing on illustrative examples from interventional cardiology, we examine current practices in cardiovascular device regulation and approval, clinical trial evaluation, adoption patterns, and postprocedural outcomes with the aim of uncovering potential mechanisms of disparities and identifying opportunities for targeted interventions.

Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than in female patients. This could be attributed to underdiagnosis in female patients or sex differences in susceptibility. Up to 30% of cases have an autosomal dominant monogenic cause, where equal sex prevalence would be expected. The aim of this systematic review, meta-analysis, and population study was to assess the sex ratio in patients with DCM, stratified by genetic status, and evaluate whether this is influenced by diagnostic bias.

Over the past decades, hypertrophic cardiomyopathy has become a contemporary treatable disease. However, limited data exist on the global trends of implantable cardioverter defibrillator (ICD) utilization and its impact on mortality/morbidity burden reduction.

The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

Some patients with aortic stenosis may require multiple valve interventions in their lifetime, and choosing transcatheter aortic valve replacement (TAVR) as the initial intervention may be appealing to many. If their transcatheter heart valve degenerates later in life, most will hope to undergo redo-TAVR. However, if redo-TAVR is not feasible, some may have to undergo surgical explantation of their transcatheter heart valve (TAVR-explant). With rising numbers of TAVR in younger patients, we address the practical implications of choosing a TAVR-first strategy. In this review we explore potential factors contributing to higher-than-expected mortality after TAVR-explant, synthesize available outcomes data for TAVR-explant for structurally degenerated valves, and describe strategies to standardize and optimize surgical techniques for TAVR-explant. We also discuss clinical outcomes of redo-TAVR within the context of limitations in currently published series and highlight the potential benefit of virtual planning to assess the feasibility of future redo-TAVR before implanting the first valve. Finally, we highlight areas for future investigation to inform management strategies in patients who may require multiple aortic valve interventions.

Advances in critical care therapies for patients with cardiogenic shock (CS), including temporary mechanical circulatory support and multidisciplinary shock teams, have led to improved survival to hospital discharge, ranging from 60% to 70%. After their index hospitalization, however, survivors of CS may continue to face cardiac as well as extracardiac sequelae of these therapies and complications for years to come. Most studies in CS have focused primarily on survival, with limited data on long-term recovery measures among survivors. In other forms of critical illness, research indicates that many intensive care unit survivors experience impairments in multiple domains, such as cognitive function, physical ability, and mental health. These impairments, collectively referred to as Post-Intensive Care Syndrome, in turn impact survivors' quality of life and future prognosis. This review identifies unique aspects of CS-related survivorship, highlights lessons learned from other forms of critical illness, and outlines future research directions to determine specific strategies to enhance recovery and survivorship after CS.

The integrative physiology of the left ventricle and systemic circulation is fundamental to our understanding of advanced heart failure and cardiogenic shock. In simplest terms, any increase in aortic stiffness increases the vascular afterload presented to the failing left ventricle. The net effect is increased myocardial oxygen demand and reduced coronary perfusion pressure, thereby further deteriorating contractile function. Although mechanical circulatory support devices should theoretically work in concert with guideline-directed medical therapy, cardiac resynchronization and inotropic and vasopressor agents designed to support myocardial performance and enhance left ventricle recovery, this does not always occur. Each therapy and intervention may result in vastly different and sometimes deleterious effects on vascular afterload. Although best described by a combination of both steady-state and pulsatile components, the latter is frequently overlooked when mean arterial pressure or systemic vascular resistance alone is used to quantify vascular afterload in advanced heart failure and cardiogenic shock. In this state-of-the-art review, we examine what is known about vascular afterload in advanced heart failure and cardiogenic shock, including the use of temporary and permanent mechanical circulatory support systems. Importantly, we outline 4 key components for a more complete assessment of vascular afterload. Unlike previous discussions on this topic, we set aside considerations of venous return and ventricular preload, as important as they are, to focus exclusively on the hydraulic load within the systemic circulation against which the impaired left ventricle must contract.