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.

Adults with patent atrial septal defect (ASD) usually find their exercise capacity satisfactory, and therefore hesitate to accept proposed surgical treatment of the heart disease. The aim of our study was to evaluate both the exercise capacity, using the cardio-pulmonary stress test, and brain natriuretic peptide (BNP) levels in asymptomatic adults with ASD. Thirty-six patients with patent secundum type ASD (aged mean 44.7 ± 8.2 years) were studied. The control group consisted of 25 healthy subjects at the mean age of 45.6 ± 6.1 years. Echocardiography and CPST were performed and BNP levels measured in all subjects. Oxygen uptake (VO_{2 max}) was lower in ASD patients than in controls (22.1 ± 5.6 vs. 30.0 ± 6.8 ml/kg/min, p = 0.00001); the VE/VO₂ slope was elevated in ASD patients compared with healthy subjects (31.3 ± 6.6 vs. 26.9 ± 3.3, p = 0.001), and exceeded 34 in 5 patients. VO_{2 max} showed a negative correlation with the pulmonary to systemic flow ratio Qp:Qs (r = –0.46, p = 0.004), and a positive correlation was found between the VE/VO₂ slope and Qp:Qs (r = 0.32, p = 0.05). BNP levels were higher in the ASD group than in the controls (60.6 ± 49.9 vs. 32.6 ± 24.5 pg/ml, p = 0.02). BNP correlated positively with RV diameter and Qp:Qs (r = 0.38 and 0.39 respectively, p = 0.03) and negatively with maximum VO₂ (r = –0.5, p = 0.004) and VO₂% (r = –0.32, p = 0.07). Conclusions: Although most adult patients with ASD perceive their exercise capacity as satisfactory, objective assessment reveals that in fact it is significantly decreased. BNP levels are increased comparing to healthy individuals. Decreased exercise capacity and increased BNP levels seem to result from right ventricular volume overload.

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IntroductionThe aim of the study was to evaluate exercise capacity using cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP) levels in patients with single or systemic right ventricles.Material and methodsThe study group included 40 patients (16 males) – 17 with transposition of the great arteries after Senning operation, 13 with corrected transposition of the great arteries and 10 with single ventricle after Fontan operation, aged 19–55 years (mean 28.8 ±9.5 years). The control group included 22 healthy individuals (10 males) aged 23–49 years (mean 30.6 ±6.1 years).ResultsThe majority of patients reported good exercise tolerance – accordingly 27 were classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in class III. Cardiopulmonary exercise test revealed significantly lower exercise capacity in study patients than in control subjects. In the study vs. control group VO2max was 21.7 ±5.9 vs. 34.2 ±7.4 ml/kg/min (p = 0.00001), maximum heart rate at peak exercise (HRmax) 152.5 ±32.3 vs. 187.2 ±15.6 bpm (p = 0.00001), VE/VCO2 slope 34.8 ±7.1 vs. 25.7 ±3.2 (p = 0.00001), forced vital capacity (FVC) 3.7 ±0.9l vs. 4.6 ±0.3 (p = 0.03), forced expiratory volume in 1 s (FEV1) 3.0 ±0.7 vs. 3.7 ±0.9l (p = 0.0002) respectively. Serum BNP concentrations were higher in study patients than in control subjects; 71.8 ±74.4 vs. 10.7 ±8.1 (pg/ml) respectively (p = 0.00001). No significant correlations between BNP levels and CpET parameters were found.ConclusionsPatients with a morphological right ventricle serving the systemic circulation and those with common ventricle physiology after Fontan operation show markedly reduced exercise capacity. They are also characterized by higher serum BNP concentrations, which do not however correlate with CpET parameters.