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.

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Active RV pacing is associated with a significant increase in TR grade. This effect is not induced by acute changes in the RV area and is unrelated to an interference with leaflet closure by the electrode.

Objectives: To identify the determinants of appropriate and inappropriate implantable cardioverterdefibrillator (ICD) discharges in patients with hypertrophic cardiomyopathy (HCM). Design: Retrospective cohort study. Setting: ICD clinic at an academic hospital. Patients: 61 patients with HCM who received ICDs for the primary or secondary prevention of sudden cardiac death (SCD). Outcome measures: (a) Analysis of appropriate and inappropriate ICD discharges; (b) predictors of ICD discharges. Results: Mean (SD) age at ICD insertion was 46 (18) years (range 10-79). Follow-up time was 40 (27) months (range 7-151). Eight patients experienced an appropriate discharge, occurring 24.5 (13.6) months after ICD insertion. Appropriate ICD intervention was more common in the secondary (36%) than the primary (8%) prevention group (p = 0.02). Inappropriate ICD discharges occurred in 20 (33%) patients. Multivariate Cox regression analysis identified two significant predictors of inappropriate ICD discharges: (a) age ,30 years at the time of ICD insertion (hazard ratio (HR) = 3.0 (95% CI 1.1 to 8.0; p = 0.03) and (b) history of atrial fibrillation (HR = 3.1 (95% CI 1.2 to 8.1; p = 0.02). Conclusions: ICDs are effective in the prevention of SCD in HCM. However, there is a high incidence of inappropriate ICD discharges.