Real world scenario of Mavacamten therapy in patients with symptomatic obstructive hypertrophic cardiomyopathy Patients

Background: There has been no causal pharmacological therapy for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) to date. Patients were rather treated symptomatically, which led to a worsening of clinical symptoms and advancing, hemodynamically relevant impairment of left ventricular outflow obstruction and output.  over time. Therefore, progressive and symptomatic HOCM is associated with poor prognosis and increased risk of sudden cardiac death. Recently, a specific therapy with the myosin ATPase inhibitor Mavacamten has been available for the treatment of these patients. Beneficial effects of Mavacamten have been shown in randomized studies, however only few data are available on HOCM patients undergoing therapy in a real-world scenario.

Methods: In our center, we treated 10 patients with symptomatic hypertrophic obstructive cardiomyopathy with mavacamten, who had previously received symptomatic therapy mainly with beta-blockers. During a one-year follow-up, repeated clinical, echocardiographic (including speckle tracking analysis and longitudinal function, 4D echo), cardiac magnetic resonance imaging (cMRI), and laboratory parameters were recorded in order to evaluate both, the effects of Mavacamten as described before in the EXPLORER-HCM study and possible additional benficial or unfavorable effects.

Results: In our center, ten patients with HOCM underwent Mavacamten therapy after careful evaluation. Patients were monitored every two to four weeks during our clinical follow up in our outpatient clinic. We were able to confirm that measurable changes in laboratory tests, clinical and echocardiographic parameters occurred after treatment for just four to eight weeks in our patient cohort. In line with the EXPLORER-HCM approval study, we observed a significant reduction in left ventricular outflow obstruction gradients (P < 0.05) after eight weeks of treatment when compared to baseline measurements. Interestingly, we did not detect significant deterioration of systolic left ventricular function, even though left ventricular ejection fraction decreased by trend.  In most cases, we determined normalization of the NTproBNP levels as well as an improvement of the NYHA class by at least one class during follow up. In none of the cases therapy had to be discontinued due to adverse effects. No serious adverse events such as relevant deterioration in left ventricular function, heart failure or relevant cardiac arrhythmias occurred in any of the patients. In addition, we were able to determine a significant reduction in septal wall thickness (p<0.05), a reduction of mitral valve insufficiency and a positive effect on diastolic dysfunction and longitudinal left ventricular function, which could be partially confirmed by MR morphology.

Conclusions: To date, there is little experience with the new specific therapy with Mavacamten in HOCM patients in an all-comers cohort. Our data support the results of the mavacamten approval study and also provide additional aspects that further beneficial effects may be expected, particularly in regards of concomitant mitral regurgitation, improvement of diastolic dysfunction and longitudinal left ventricular function. However, due to the small number of patients, our results are rather observational. Therefore, larger randomized studies are needed to obtain further reliable data on long-term effects and side effects as well as suitability for long-term therapy.