Background Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1•5 mL/kg per min or greater increase in peak oxygen consumption (pVO 2) and at least one NYHA class reduction or a 3•0 mL/kg per min or greater pVO 2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO 2 , NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545.

Background-Thoracic radiation results in radiation-associated heart disease (RAHD), often requiring cardiothoracic surgery (CTS). We sought to measure long-term survival in RAHD patients undergoing CTS, to compare them with a matched control population undergoing similar surgical procedures, and to identify potential predictors of long-term survival. Methods and Results-In this retrospective observational cohort study of patients undergoing CTS, matched on the basis of age, sex, and type/time of CTS, 173 RAHD patients (75% women; age, 63±14 years) and 305 comparison patients (74% women; age, 63±4 years) were included. The vast majority of RAHD patients had prior breast cancer (53%) and Hodgkin lymphoma (27%), and the mean time from radiation was 18±12 years. Clinical and surgical parameters were recorded. The preoperative EuroSCORE and all-cause mortality were recorded. The mean EuroSCOREs were similar in the RAHD and comparison groups (7.8±3 versus 7.4±3, respectively; P=0.1). Proximal coronary artery disease was higher in patients with RAHD versus the comparison patients (45% versus 38%; P=0.09), whereas redo CTS was lower in the RACD versus the comparison group (20% versus 29%; P=0.02). About two thirds of patients in either group had combination surgical procedures. During a mean follow-up of 7.6±3 years, a significantly higher proportion of patients died in the RAHD group than in the comparison group (55% versus 28%; P<0.001). On multivariable Cox proportional hazard analysis, RAHD (2.47; 95% confidence interval, 1.82-3.36), increasing EuroSCORE (1.22; 95% confidence interval, 1.16-1.29), and lack of β-blockers (0.66; 95% confidence interval, 0.47-0.93) were associated with increased mortality (all P<0.01). Conclusions-In patients undergoing CTS, RAHD portends increased long-term mortality. Alternative treatment strategies may be required in RAHD to improve long-term survival. (Circulation. 2013;127:1476-1484.) Key Words: heart disease ◼ radiation ◼ surgery ◼ survival © 2013 American Heart Association, Inc. history of a documented malignancy requiring chest irradiation who subsequently developed coronary/valvular disease significant enough to require cardiothoracic surgery (radiation heart disease group). The diagnosis of radiation heart disease was made after a thorough clinical and echocardiographic evaluation by experienced cardiologists. In this group, type of prior malignancy and area of radiation were ascertained. When available, the year of the last radiation dose was recorded. All patients were cleared by oncology for a cardiac surgical procedure. The second group consisted of 305 patients without a history of malignancy or chest irradiation (comparison group) who were matched with group 1 for type and time of cardiothoracic surgery, age, and sex (in that order). In the vast majority of cases, we were able to achieve a 1:2 match of radiation to comparison group. In 41 instances, there was only a 1:1 match. Clinical DataData were assembled after individual analysis of electronic medical records after...

We performed a systematic review of the current state of the literature regarding the natural history and outcomes of bicuspid aortic valve (BAV). PubMed and the reference lists of the included articles were searched for relevant studies reporting on longitudinal follow-up of BAV cohorts (mean follow-up ≥2 years). Studies limited to patients undergoing surgical interventions were excluded. 13 studies (11 502 patients with 2-16 years of follow-up) met the inclusion criteria. There was a bimodal age distribution (30-40 vs ≥50 years), with a 3:1 male to female ratio. Complications included moderate to severe aortic regurgitation (prevalence 13%-30%), moderate to severe aortic stenosis (12%-37%), infective endocarditis (2%-5%) and aortic dilatation (20%-40%). Aortic dissection or rupture was rare, occurring in 38 patients (0.4%, 27/6446 in native BAV and 11/2232 in post). With current aggressive surveillance and prophylactic surgical interventions, survival in three out of four studies was similar to that of a matched general population. In this systematic review, valvular dysfunction warranting surgical intervention in patients with BAV were common, aortic dissection was rare and, with the current management approach, survival was similar to that of the general population.

Advances in diagnostic imaging have increased the recognition of coexisting transthyretin cardiac amyloidosis (ATTR-CA) and severe aortic stenosis (AS), with a reported prevalence between 8-16%. In this prospective study, we aimed to evaluate the implications of ATTR-CA on outcomes after transcatheter aortic valve replacement (TAVR).

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