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Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, with an overall prevalence of at least 1:500 in the adult population although only a fraction of affected patients come to clinical recognition. It is also the most common cause of sudden cardiac death in young adults and a major cause of morbidity caused by chronic heart failure symptoms. However, more than half a century since the original description of the disease, there is no currently approved therapy for the treatment of patients with HCM, and to date there have been only 5 randomized studies of medical therapies in HCM. As such, unmet medical need in HCM has been highlighted by the National Heart, Lung, and Blood Institute (NHLBI) as a research priority. Encouragingly, the infrastructure needed to conduct rigorous clinical trials in HCM has recently emerged because of the heightened awareness and understanding of the disease, development of clinical centers of excellence, and advances in diagnostic imaging. In this article, we will discuss the complex pathophysiology of HCM, review the current therapeutic landscape, describe new mechanistic insights into the central role of the late sodium current in HCM, and introduce the scientiic rationale and execution of the Impact of Late Sodium Current Inhibition on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy (LIBERTY-HCM) trial, the largest randomized, double-blind, placebo controlled clinical trial, now underway, designed to evaluate the effect of a novel pharmacological approach in patients with symptomatic HCM. [ABSTRACT FROM AUTHOR]

Multiple studies have demonstrated strong associations between cardiorespiratory fitness and lower cardiovascular disease mortality. In contrast, little is known about associations of fitness with nonfatal cardiovascular events.Linking individual participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 20 642 participants (21% women) with fitness measured at the mean age of 49 years and who survived to receive Medicare coverage from 1999 to 2009. Fitness was categorized into age- and sex-specific quintiles (Q) according to Balke protocol treadmill time with Q1 as low fitness. Fitness was also estimated in metabolic equivalents according to treadmill time. Associations between midlife fitness and hospitalizations for heart failure and acute myocardial infarction after the age of 65 years were assessed by applying a proportional hazards model to the multivariate failure time data. After 133 514 person-years of Medicare follow-up, we observed 1051 hospitalizations for heart failure and 832 hospitalizations for acute myocardial infarction. Compared with high fitness (Q4-5), low fitness (Q1) was associated with a higher rate of heart failure hospitalization (14.3% versus 4.2%) and hospitalization for myocardial infarction (9.7% versus 4.5%). After multivariable adjustment for baseline age, blood pressure, diabetes mellitus, body mass index, smoking status, and total cholesterol, a 1 unit greater fitness level in metabolic equivalents achieved in midlife was associated with ≈20% lower risk for heart failure hospitalization after the age of 65 years (men: hazard ratio [95% confidence intervals], 0.79 [0.75-0.83]; P<0.001 and women: 0.81 [0.68-0.96]; P=0.01) but just a 10% lower risk for acute myocardial infarction in men (0.91 [0.87-0.95]; P<0.001) and no association in women (0.97 [0.83-1.13]; P=0.68).Fitness in healthy, middle-aged adults is more strongly associated with heart failure hospitalization than acute myocardial infarction outcomes decades later in older age. [ABSTRACT FROM AUTHOR]

Background: Telomere shortening has been proposed as a marker of biological aging. Whether leukocyte telomere length is associated with mortality among patients with stable coronary artery disease (CAD) is unknown., Methods and Results: We measured leukocyte telomere length in 780 patients with stable CAD in a prospective cohort study. Participants were categorized by quartiles of telomere length. Hazard Ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure (HF) hospitalization, and cardiovascular (CV) events. After 4.4 years of follow-up there were 166 deaths. Compared with participants in the highest telomere length quartile, those in the lowest quartile were at increased risk of death (age-adjusted HR 1.8; 95% CI 1.2 to 2.9). After multivariate adjustment for clinical (HR 2.1; CI 1.3 to 3.3), inflammatory (HR 2.0; CI 1.2 to 3.2), and echocardiographic (HR 1.9; CI 1.0 to 3.5) risk factors, patients in the lowest quartile of telomere length remained at significantly increased risk of death compared to those in the highest quartile. Patients in the lowest quartile of telomere length were also at significantly increased risk of HF hospitalization (HR 2.6; CI 1.1 to 6.0) but not CV events (HR 1.7; CI 0.9 to 3.5)., Conclusions: Reduced leukocyte telomere length is associated with all-cause mortality in patients with stable CAD. The prognostic value of short telomeres in predicting death is not completely captured by existing clinical, inflammatory, and echocardiographic markers of risk.