Abstract 4144145: Mavacamten-induced Augmentation of Exercise Strain is the Mechanical Basis for Improvement in Exercise Capacity in Obstructive Hypertrophic Cardiomyopathy

Background : Mavacamten reduces left ventricular outflow tract gradients (LVOTg), improves symptoms and increases exercise capacity in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients. We investigated the potential myocardial mechanical basis for improved exercise capacity in these patients. Methods: We evaluated symptoms, exercise capacity in metabolic equivalents (METs), LVOTg at rest, at Valsalva and peak-exercise, and global left ventricular longitudinal strain (GLS) at rest and peak-exercise in patients before and during mavacamten therapy. Results: oHCM patients at a single tertiary center (n=22, 56% female, mean age 64 ± 12 years) were evaluated pre- and post-mavacamten initiation (Table). Mean duration of treatment was 22 ± 14 weeks. There was significant improvement in NYHA class – proportion of NYHA I increased from 0 to 64% and NYHA II and III decreased from 77 to 34% and 23 to 5%, respectively (Figure B). All patients underwent a symptom-limited Bruce protocol treadmill stress echocardiogram and there was a significant improvement in exercise capacity pre- vs. on-mavacamten (7.6± 3.4 vs. 8.6± 3.4 METs, respectively, p 0.01). There was a significant decrease in LVOTg at rest, at Valsalva and post-exercise (47 ± 43 vs. 9.8 ±6 mmHg, 82 ± 46 vs 20 ± 19 and 114 ± 54 vs. 43 ± 40 mmHg, respectively, all p < 0.001). Rest GLS did not change pre- vs. on-Mavacamten (15 ± 3 vs. 16 ± 3%, p 0.07). However, peak-exercise GLS improved significantly (16 ± 4 vs. 18 ± 4%, pre vs. on-mavacamten, p < 0.01) (Figure A). Conclusion: Mavacamten-induced augmentation of exercise strain may be the mechanical basis for exercise capacity improvements in oHCM. Rest GLS non-significantly increased on mavacamten. Our results will need validation in a larger cohort.