Real-world symptom and echocardiographic improvement in obstructive HCM patients treated with mavacamten: evidence of favorable disease modification

Abstract Background Mavacamten is approved for clinical use in symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), as it reduces the eligibility for septal reduction therapy (SRT) with sustained improvement in left ventricular outflow tract gradients (LVOTG) and symptoms, along with favorable cardiac remodeling. Objective We sought to assess symptomatic improvement, serial echocardiographic changes (including strain) and safety in oHCM patients treated with commercial mavacamten in a multi-hospital referral center. Methods We included 244 oHCM patients (baseline mean age 64 years, 57% female, 21% atrial fibrillation AF, 51% New York Heart Association NYHA class III, 82% on betablockers) who were treated with commercial mavacamten for atleast 3 months (171 patients were treated for at least 12 months). Various echocardiographic measurements (including LV ejection fraction, LVOTG, LV wall thickness, LV mass index, E/e’, LV global longitudinal strain (GLS), left atrial volume index LAVI, LA GLS, right ventricular RV GLS and RV function) were measured according to guidelines. Results Distribution of NYHA Classes were as follows: 3 months (20% Class I, 61% Class II and 18% Class III), 6 months (28% Class I, 60% Class II and 10% Class III) and 12 months (35% Class I, 57% Class II and 8% Class III). At a mean follow-up of 1.02±0.4 years, there were significant and sustained improvements in various echocardiographic parameters at baseline, 3, 6 and 12 months as shown in Figure. Eleven (4.5%) patients needed temporary interruption, of which 3 needed permanent discontinuation of mavacamten due to side-effects and LVEF30%. There was 1 death (due to noncardiac causes), 7 (3%) admissions for heart failure and 14 (6%) patients with new-onset AF, while 1 patient proceeded with SRT due to persistent symptoms. At last visit, mavacamten doses were as follows: 2.5 mg (n=39 16%), 5 mg (n=120 49%), 10 mg (n=63 26%) and 15 mg (n=18 7%). Conclusions In a real-world report on symptomatic oHCM patients treated with commercially available mavacamten at multi-hospital referral center, in addition to significant symptomatic and LVOTG improvement, there was sustained and significant favorable cardiac remodeling including improvements in LV wall thickness, LV mass, LV strain, RV function and strain, LV diastolic function and LA size and function. Mavacamten was tolerated safely with the lowest doses providing adequate efficacy and symptom relief.Echo changes on clinical mavacamten