Will Elevated Left Ventricle Filling Pressures Decrease by a Group Exercise Program in Patients With Hypertrophic CardioMyopathy?

Hypertrophic Cardiomyopathy Clinical Trial

— WEDGE-HCM  

Official title:

Will Elevated Left Ventricle Filling Pressures Decrease by a Group Exercise Program in Patients With Hypertrophic CardioMyopathy? - A Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537183
• Other study ID #: 63446
• Status: Completed
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: April 1, 2023

Study information

• Verified date: April 2023
• Source: Bispebjerg Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Other:
• Exercise training
12 weeks, 3 hours a week, moderate intensity exercise training

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Bispebjerg Hospital	Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Left ventricular fibrosis	(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.	12 weeks
Primary	Change from baseline to follow-up in PCWP at 25 W	Pulmonary capillary wedge pressure (mmHg)	12 weeks
Secondary	Pulmonary capillary wedge pressure	At rest, at 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg)	12 weeks
Secondary	Workload adjusted Pulmonary capillary wedge pressure	At rest, at 25% and 50% of the maximum workload and at maximum workload, measured as mmHg/kg/W	12 weeks
Secondary	Systemic vascular resistance	Resting and exercise systemic vascular resistance at rest, 25 W, 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg)	12 weeks
Secondary	Exercise capacity	Measured as watt at maximum workload	12 weeks
Secondary	Heart rate	At rest, during exercise and at maximum exercise capacity (beats/min)	12 weeks
Secondary	Blood pressure	At rest, at maximum workload, 6 minutes after cease of workload (mmHg)	12 weeks
Secondary	Cardiac index	At rest, 25W and at maximum workload (L/min/m2):	12 weeks
Secondary	Arterio-venous difference	At rest, 25W and at maximum workload (ml O2/L)and workload corrected (mlO2/L/W)	12 weeks
Secondary	VO2 max	Measered as ml O2/min/kg	12 weeks
Secondary	Quality of life questionnaire	Measured by Kansas City Cardiomyopathy score	12 weeks
Secondary	NT-Pro-BNP	(pmol/L)	12 weeks
Secondary	Troponin-T	(mmol/L)	12 weeks
Secondary	Echocardiographic parameters	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).	12 weeks