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.