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Background and Aims: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten., Methods: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion., Results: At the latest data cut-off, 211 (91.3%) of the 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the Week 156 and 180 visits, respectively. Sustained reductions from baseline to Week 180 occurred in left ventricular outflow tract gradients [mean (standard deviation): resting, -40.3 (32.7) mmHg; Valsalva, -55.3 (33.7) mmHg], N-terminal pro B-type natriuretic peptide [median (interquartile range): -562 (-1162.5, -209) ng/L], and EQ-5D-5L score [mean (standard deviation): 0.09 (0.17)]. Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (Week 24) and 63.9% (Week 180). At Week 180, 74 (77.9%) of the 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten)., Conclusions: Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate the effect of treatment with aficamten on biomarker concentrations., Methods: Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and evaluated whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity., Results: Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% confidence interval 76%-83%, P < .001) and hs-cTnI by 41% (95% confidence interval 32%-49%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. N-Terminal pro-B-type natriuretic peptide reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints., Conclusions: N-Terminal pro-B-type natriuretic peptide and hs-cTnI concentrations are associated with key variables in obstructive hypertrophic cardiomyopathy. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Adults who engage in leisure-time physical activity (LTPA) have a reduced risk of developing heart failure. We hypothesized that high levels of LTPA are associated with diminished adverse age-related changes in cardiac structure and function., Methods and Results: We studied 4342 Atherosclerosis Risk in Communities Study participants free of cardiovascular disease who underwent standardized echocardiography. In a cross-sectional analysis, we related LTPA (poor, intermediate, or ideal) to cardiac structure and function. We also related cumulative average LTPA over 24 years and changes in LTPA categories to echocardiographic measures. Cross-sectional analysis demonstrated that ideal LTPA, compared with poor LTPA, was associated with better diastolic function [prevalence of normal diastolic function: 39.8% vs. 31.5%, P < 0.001; mean E/E' ratio (95% CI): 9.8 (9.6, 9.9) vs. 10.4 (10.2, 10.5), P = 0.001] and better systolic function [left-ventricular (LV) longitudinal strain: -18.3 (-18.4, -18.2) vs. -17.9 (-18.0, -17.8), P < 0.001] after adjusting for age, sex, race, and centre. Higher cumulative average LTPA over 24 years or an improvement in LTPA category were also, respectively, related to a more favourable E/E' ratio (P < 0.0001, P = 0.004) and longitudinal LV strain (P = 0.0002, P = 0.002)., Conclusion: Ideal LTPA, higher average levels of LTPA over a 24-year period, and an improvement in LTPA even later in life were associated with more favourable indices of LV diastolic and systolic function in older adults. Sustaining higher levels of LTPA, and even increasing physical activity later in life, may be beneficial for older adults in attenuating expected age-related changes in cardiac structure and function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)