Hypertrophic Cardiomyopathy
Conditions
Keywords
hypertrophic cardiomyopathy, exercise training, PCWP
Brief summary
Aims and objectives: The primary objective of this study is to assess whether a structured exercise program improves cardiac relaxing properties in patients with hypertrophic cardiomyopathy (HCM). Background: HCM is a hereditary disease in which the myocardium becomes thickened without an identifiable cause (other than genetic). It is the most common genetic cardiovascular disease with an estimated prevalence of 1/500 (i.e. 10.000 affected individuals in Denmark). The majority of patients with HCM suffers from shortness of breath and reduced exercise capacity due to increased left ventricular (LV) stiffness. Exercise training has been shown to improve exercise capacity and symptoms in patients with HCM, but the mechanisms responsible for this improvement are not known. Methods and materials: The study is a randomized, single blinded, prospective, controlled clinical trial. Eighty patients are recruited from outpatient clinics in the Capital Region of Denmark. Patients are randomized in a 1:1 ratio to 12 week of moderate-intensity exercise training or usual activity level. Assessments will include right heart catheterization, echocardiography, cardiopulmonary exercise testing, blood-samples, quality of life, and, in a subgroup of patients, cardiac magnetic resonance imaging. The primary end-point is change in LV filling pressure assessed as pulmonary capillary wedge pressure at 25 W workload. Expected outcome and perspectives: The investigators hypothesize that an exercise training program will reduce cardiac stiffness and improve symptoms in patients with HCM. Training of HCM patients has long been debated and the topic is poorly researched. The effects of exercise on hemodynamics in HCM patients are unknown and a better understanding of these mechanisms is pivotal for improving treatment.
Interventions
OTHERExercise training
12 weeks, 3 hours a week, moderate intensity exercise training
Sponsors
Rigshospitalet, Denmark
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥18 years at the time of screening 2. Documented phenotypic HCM (maximal wall thickness ≥15mm, or ≥13mm in a first degree relative with a definite or likely disease causing genetic mutation (appendix 1) 3. Not exercising regularly (dedicated moderate or high-intensity exercise \>1 hour weekly) 4. NYHA class I-IV.
Exclusion criteria
1. Phenocopies (i.e. syndromes, metabolic disorders (appendix 2)) 2. A history of exercise induced syncope within the last year, severe angina (CCS III-IV), hemodynamically severe valvular disorders 3. Scheduled septal reduction therapy, less than 3 months after septal reduction therapy or known LVOT gradient above 30 mmHg at rest 4. Severe hypertension (Systolic blood pressure \>200 mmHg or diastolic blood pressure \>110 mmHg). 5. Inability to exercise due to orthopedic or other non-cardiovascular limitations. 6. Pregnancy 7. Changes in medication that may affect exercise capacity and/or hemodynamics (i.e. beta blockers and calcium channel blockers) 8. Any condition (eg, psychiatric illness) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to follow-up in PCWP at 25 W | 12 weeks | Pulmonary capillary wedge pressure (mmHg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary capillary wedge pressure | 12 weeks | At rest, at 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg) |
| Workload adjusted Pulmonary capillary wedge pressure | 12 weeks | At rest, at 25% and 50% of the maximum workload and at maximum workload, measured as mmHg/kg/W |
| Systemic vascular resistance | 12 weeks | Resting and exercise systemic vascular resistance at rest, 25 W, 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg) |
| Exercise capacity | 12 weeks | Measured as watt at maximum workload |
| Heart rate | 12 weeks | At rest, during exercise and at maximum exercise capacity (beats/min) |
| Blood pressure | 12 weeks | At rest, at maximum workload, 6 minutes after cease of workload (mmHg) |
| Arterio-venous difference | 12 weeks | At rest, 25W and at maximum workload (ml O2/L)and workload corrected (mlO2/L/W) |
| VO2 max | 12 weeks | Measered as ml O2/min/kg |
| Quality of life questionnaire | 12 weeks | Measured by Kansas City Cardiomyopathy score |
| NT-Pro-BNP | 12 weeks | (pmol/L) |
| Troponin-T | 12 weeks | (mmol/L) |
| Echocardiographic parameters | 12 weeks | At rest: E/e'-ratio, E/A-ratio, deceleration time, LVOT gradient (mmHg). During exercise from 25W to maximum workload: E/e'-ratio, E/A-ratio, deceleration time, LVOT gradient(mmHg). |
| Cardiac index | 12 weeks | At rest, 25W and at maximum workload (L/min/m2): |
Other
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular fibrosis | 12 weeks | (assessed as late gadolinum enhancement) and extracellular volume (assessed using T1-mapping) will be assessed in the subgroup of patients without contraindications to CMR and will be correlated to LV filling pressures. |
Countries
Denmark
Outcome results
None listed