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.

Use of anabolic androgenic steroids (AASs) is associated with increased mortality, and case reports have suggested that some of these deaths are due to cardiovascular disease. However, the epidemiology of cardiovascular disease in AAS users is still relatively unexplored. This study aimed to measure the incidence of cardiovascular disease in male AAS users and to compare these rates with those of a cohort from the general population matched by age and sex.

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.

Although cell therapy has emerged as a promising approach to promote neovascularization, its effects are mostly limited to capillaries. To generate larger or more stable vessels, layering of mural cells such as smooth muscle cells (SMCs) or pericytes is required. Recently, direct reprogramming approaches have been developed for generating SMCs. However, such reprogrammed SMCs lack genuine features of contractile SMCs, a native SMC phenotype; thus, their therapeutic and vessel-forming potential in vivo was not explored. Therefore, we aimed to directly reprogram human dermal fibroblasts toward contractile SMCs (rSMCs) and investigated their role for generating vascular mural cells in vivo and their therapeutic effects on ischemic disease.

It remains challenging to determine which hypertrophic cardiomyopathy (HCM) family members will subsequently develop HCM. Standard 2-dimensional and conventional Doppler echocardiography have been unable to reliably distinguish HCM genotype-positive and phenotype-negative (G+P-) from genotype-negative and phenotype-negative (G-P-) family members. We aimed to determine if advanced echocardiographic modalities can discriminate HCM G+P- from G-P- individuals.

TTN (titin) is the third myofilament type of the cardiac sarcomere and performs important functions that include generating passive tension. Changes in TTN expression are associated with cardiac dysfunction, and TTN is one of the main genes linked to dilated cardiomyopathy (DCM). DCM is frequently associated with changes in the expression of N2BA (compliant cardiac TTN isoform), 1 of the 2 major TTN isoforms found in the heart (the other isoform being the N2B [stiff cardiac TTN isoform]). Whether altered expression of N2BA TTN causes DCM or is a secondary change remains unclear.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib.

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.

It is difficult to identify patients with atrial fibrillation (AF) most likely to respond to ablation. While any arrhythmia patient may recur after acutely successful ablation, AF is unusual in that patients may have long-term arrhythmia freedom despite a lack of acute success. We hypothesized that acute and chronic AF ablation outcomes may reflect distinct physiology and used machine learning of multimodal data to identify their phenotypes.

The developmental diversity among smooth muscle cells (SMCs) plays a crucial role in segment-specific aortic diseases. However, traditional genetic approaches are inadequate for enabling in vivo analysis of disease susceptibility associated with cellular origin. There is an urgent need to build genetic technologies that target different developmental origins to investigate the mechanisms of aortopathies, thereby facilitating the development of effective therapeutics.

The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses.

Cytokinesis is the last step in the eukaryotic cell cycle, which physically separates a mitotic cell into 2 daughter cells. A few days after birth in mouse cardiomyocytes, DNA synthesis occurs without cytokinesis, leading to the majority of cardiomyocytes becoming binucleated instead of generating 2 daughter cells with 1 nucleus each. This results in cell cycle arrest of cardiomyocytes, and the mouse heart is no longer able to regenerate. A longstanding unanswered question is whether binucleation of cardiomyocytes is a result of cytokinesis failure.

The optimal coronary stenting technique for true left main bifurcation lesions is uncertain. EBC MAIN (European Bifurcation Club Left Main Trial) aimed to evaluate clinical outcomes of a stepwise provisional strategy compared with a systematic dual-stent approach.

Although combination antiretroviral therapy has increased life expectancy in people living with HIV, it has led to a marked increase in the prevalence of hypertension, the cause of which is unknown. Despite combination antiretroviral therapy, HIV-derived proteins remain expressed and produced by CD4+ T lymphocytes in people living with HIV. However, their contribution to HIV-associated hypertension and impaired endothelium-dependent relaxation remains ill defined.

Vascular Ehlers-Danlos syndrome is a rare genetic disorder characterized by defective type III collagen and a high risk of arterial morbidity and mortality. Several cardiovascular drugs are used for treatment, including celiprolol, but no controlled trial in this condition has been conducted to date. We hypothesized the benefit of the addition of an angiotensin II receptor blocker.

Infective endocarditis (IE) can be challenging to diagnose. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]-fluoro-d-glucose ([18F]FDG) is recommended as a diagnostic tool in the guidelines, but holds limitations. The aim of this study was to compare the tracer uptake between the novel [64Cu]Cu-DOTATATE, which has low cardiac uptake and does not require fasting or dietary restrictions, and [18F]FDG in patients with IE and examine the sensitivity and specificity.

Immune checkpoint inhibitors (ICIs), though revolutionary in cancer treatment, may accelerate atherosclerosis by inducing arterial inflammation. Due to a lack of controlled studies, the capacity of arterial 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake in patients with cancer to detect this arterial inflammation remains unclear.

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.