Mavacamten Enables Exercise in Hypertrophic Obstructive Cardiomyopathy

Official title

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

Overview

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

• Other Exercise training
  Supervised, combined endurance and resistance training

Primary outcome measures

• Incidence of Treatment-Emergent Adverse Events [Time frame: 6 weeks]

Secondary outcome measures (7)

• Change of resting left ventricular ejection fraction [Time frame: 6 weeks]
• Change of tissue Doppler velocity during peak exercise [Time frame: 6 weeks]
• Change of minute ventilation to carbon dioxide production [Time frame: 6 weeks]
• Change of Kansas City Cardiomyopathy Score [Time frame: 6 weeks]
• Change of N-terminal pro-B-type natriuretic peptide and troponin I [Time frame: 6 weeks]
• Differences of incidence of atrial fibrillation, atrial or ventricular tachycardia on electrocardiograms [Time frame: 6 weeks]
• Change of peak oxygen consumption [Time frame: 6 weeks]

Eligibility criteria

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%

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Other

Study locations

Germany · 1 center

• Technical University Munich — Munich

Publications

• Sachdev V, Sharma K, Keteyian SJ, Alcain CF, Desvigne-Nickens P, Fleg JL, Florea VG, Franklin BA, Guglin M, Halle M, Leifer ES, Panjrath G, Tinsley EA, Wong RP, Kitzman DW; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and American College of Cardiology. Supervised Exercise PMID 36943925
• Ommen SR, Ho CY, Asif IM, Balaji S, Burke MA, Day SM, Dearani JA, Epps KC, Evanovich L, Ferrari VA, Joglar JA, Khan SS, Kim JJ, Kittleson MM, Krittanawong C, Martinez MW, Mital S, Naidu SS, Saberi S, Semsarian C, Times S, Waldman CB; Peer Review Committee Members. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Associati PMID 38718139
• Bertero E, Canepa M, Olivotto I. Hypertrophic cardiomyopathy evolving management: American Heart Association/American College of Cardiology vs. European Society of Cardiology guidelines. Eur Heart J. 2025 Jan 21;46(4):359-361. doi: 10.1093/eurheartj/ehae507. No abstract available. PMID 39504436
• Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, Bezzina CR, Biagini E, Blom NA, de Boer RA, De Winter T, Elliott PM, Flather M, Garcia-Pavia P, Haugaa KH, Ingles J, Jurcut RO, Klaassen S, Limongelli G, Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Van Tintelen JP, Ware JS, Kaski JP; ESC Scientific Document Group. 2023 ESC Guidelines for the management of car PMID 37622657
• Kim JH, Baggish AL, Levine BD, Ackerman MJ, Day SM, Dineen EH, Guseh Ii JS, La Gerche A, Lampert R, Martinez MW, Papadakis M, Phelan DM, Shafer KM; American Heart Association Leadership Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Peripheral Vascu PMID 39976316
• Basu J, Nikoletou D, Miles C, MacLachlan H, Parry-Williams G, Tilby-Jones F, Bulleros P, Fanton Z, Baker C, Purcell S, Lech C, Chapman T, Sage P, Wahid S, Sheikh N, Jayakumar S, Malhotra A, Keteepe-Arachi T, Gray B, Finocchiaro G, Carr-White G, Behr E, Tome M, O'Driscoll J, Chis Ster I, Sharma S, Papadakis M. High intensity exercise programme in patients with hypertrophic cardiomyopathy: a randomi PMID 40037382
• Olivotto I, D'Ascenzi F. Exercise prescription in hypertrophic cardiomyopathy: Dr Lown's lesson to break taboos. Eur Heart J. 2025 May 14;46(19):1816-1818. doi: 10.1093/eurheartj/ehae659. No abstract available. PMID 40037289
• Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obst PMID 32871100

Identifiers

NCT: NCT07077005 · 2025-125-S-SB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗