Cardiomyopathy, Hypertrophic
Conditions
Keywords
exercise capacity, mavacamten, safety, exercise training
Brief summary
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.
Detailed description
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.
Interventions
OTHERExercise training
Supervised, combined endurance and resistance training
Sponsors
Technical University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Investigator)
Masking description
The investigator will have no knowledge of group allocation.
Intervention model description
Patients will be allocated to an exercise intervention group undergoing combined endurance and resistance training for 6 weeks or to a usual care group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 6 weeks | Safety is defined by the abscence of adverse or serious adverse events during exercise training or within 1h of exercise termination. Adverse events include non-sustained ventricular tachycardia (nsVT) and atrial fibrillation. Serious adverse events contain hospitalization due to cardiovascular events, sustained ventricular tachycardia, nsVT with hemodynamic compromise, syncope, cardiac arrest and sudden cardiac death. Higher scores mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of tissue Doppler velocity during peak exercise | 6 weeks | Changes of tissue Doppler velocity (average between medial and lateral velocities) during peak exercise between visit 1 and visit 2 between the exercise and usual care group. Higher scores mean a better diastolic function. |
| Change of minute ventilation to carbon dioxide production | 6 weeks | Changes of minute ventilation to carbon dioxide production between visit 1 and visit 2 between the exercise and usual care group. Higher scores mean a worse outcome. |
| Change of Kansas City Cardiomyopathy Score | 6 weeks | Changes of quality of life between visit 1 and visit 2 between the exercise and usual care group. Quality of life is assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ), a difference of at least five points is considered significant. KCCQ ranges from 0 to 100 points, while 0 means worst quality of life, 100 being best quality of life. |
| Change of resting left ventricular ejection fraction | 6 weeks | Changes of resting left ventricular ejection fraction between visit 1 and visit 2 between the exercise and usual care group. |
| Differences of incidence of atrial fibrillation, atrial or ventricular tachycardia on electrocardiograms | 6 weeks | Between group differences of incidence of atrial fibrillation, atrial tachycardia or ventricular tachycardia on electrocardiograms triggered by the smart watch electrocardiograms or displayed by electrocardiograms during visits. |
| Change of peak oxygen consumption | 6 weeks | Changes of peak oxygen consumption between visit 1 and visit 2 between the exercise and usual care group. A change of 1.5mL/kg/min is considered significant. Higher scores mean a better outcome. |
| Change of N-terminal pro-B-type natriuretic peptide and troponin I | 6 weeks | Changes of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP, pg/ml) and troponin I (pg/ml) between visit 1 and visit 2 between the exercise and usual care group. Higher scores mean a worse outcome. |
Countries
Germany
Contacts
Primary ContactSimon Wernhart, MD
Backup ContactMartin Halle, Professor
Outcome results
None listed