Mavacamten Enables Exercise in Hypertrophic Obstructive Cardiomyopathy

MavaEnEx-HOCM: Mavacamten Enables Exercise Training in Patients With Hypertrophic Obstructive CardioMyopathy. A Pilot Study

Patients with hypertrophic obstructive cardiomyopathy and New York Heart Association Class I-II under stable treatment with mavacamten (at least 12 weeks without change of dosage) and a peak left ventricular outflow tract obstruction <50mmHg undergo either 6 weeks of structured moderate intensity endurance and resistance training (supervised, 3x/week, intervention, IT) or usual care (UC). Patients within 1 hour of travel to the training venue will be referred to IT, while those with more than 1 hour will join UC.

At baseline (visit 1, V1) and after 6 weeks of exercise intervention (visit 2, V2) all patients undergo a medical exam, resting and stress echocardiography and receive a questionnaire on the quality of life (Kansas City Cardiomyopathy Questionnaire). Cardiac biomarkers are assessed. 3 hours after stress echocardiography cardiopulmonary exercise testing is performed to measure peak oxygen consumption (VO2peak).

The primary outcome is safety. Secondary outcomes include the change of VO2peak, changes in cardiac biomarkers, resting and stress echocardiographic variables, quality of life and variables of cardiopulmonary exercise testing from V1 to V2.

Patients with hypertrophic obstructive cardiomyopathy and New York Heart Association Class I-II under stable treatment with mavacamten (at least 12 weeks without change of dosage) and a peak left ventricular outflow tract obstruction <50mmHg at rest and during peak exercise undergo either 6 weeks of structured moderate intensity endurance and resistance training (supervised, 3x/week, intervention group, IT) or usual care (UC). UC will receive standard recommendations on physical activity but no supervised training. All patients receive smart watches and electrocardiograms can be triggered upon symptoms.

Patients previously treated with transcoronary septal ablation or surgical myectomy, more than low grade valve pathology during resting echocardiography, syncope or sustained ventricular tachycardia within 6 months prior to study inclusion, prior implantable cardioverter defibrillator implantation, persistent or permanent atrial fibrillation (AF) without anticoagulation for ≥4 weeks or paroxysmal or intermittent AF on screening electrocardiogram, or a corrected QT-interval (Fridericia-formula) ≥ 500 ms will be excluded. Patients with a Sudden Cardiac Death Risk Score ≥4% are excluded from the study.

Due to the rare nature of the disease and the large geographical variation, patients within 1 hour of travel to the training site will join IT, patients travelling more than 1 hour will be grouped into UC.

At baseline (visit 1, V1) and after 6 weeks of exercise intervention (visit 2, V2) all patients undergo a medical exam, resting and stress echocardiography and receive a questionnaire on the quality of life (Kansas City Cardiomyopathy Questionnaire). Cardiac biomarkers are assessed. 3 hours after stress echocardiography cardiopulmonary exercise testing (CPET) is performed to measure peak oxygen consumption (VO2peak).

The primary outcome is safety (no ventricular arrhythmias during exercise intervention or within 1 hour after completion of exercise). Secondary outcomes include changes in VO2peak, changes in cardiac biomarkers, resting and stress echocardiographic variables, quality of life and CPET variables. Physicians performing the echocardiographies and CPET analyses will be blinded to group allocation.

Inclusion Criteria:

• Age ≥18 years of age
• Diagnosis of hypertrophic obstructive cardiomyopathy
• ≥12 weeks of unchanged dosage of mavacamten
• Peak left ventricular outflow tract gradient ≤ 50 mmHg at rest and during stress echocardiography
• Left ventricular ejection fraction ≥50% at study inclusion
• New York Heart Association classes I-II

Exclusion Criteria:

• Syncope or sustained ventricular tachycardia within 6 months prior to study inclusion
• Corrected QT-interval (Fridericia-formula) ≥ 500 ms
• Paroxysmal or intermittent atrial fibrillation (AF) on screening electrocardiogram
• Persistent or permanent AF without anticoagulation for ≥4 weeks
• Previous transcoronary ablation of septal hypertrophy or surgical myectomy
• Ventricular tachycardia, significant ST-elevation or depression upon baseline cardiopulmonary exercise testing
• ≥ grade II valve insufficiencies or stenoses during resting echocardiography
• Prior implantable cardioverter defibrillator-implantation
• Sudden Cardiac Death Risk Score ≥4%