Will Elevated Left Ventricle Filling Pressures Decrease by a Group Exercise Program in Patients With Hypertrophic CardioMyopathy? (WEDGE-HCM)

• ClinicalTrials.gov Identifier: NCT03537183
• Recruitment Status: Recruiting
• First Posted: May 25, 2018
• Last Update Posted: March 3, 2022
• Sponsor: Bispebjerg Hospital
• Collaborator: Rigshospitalet, Denmark
• Information provided by (Responsible Party): Helga Gudmundsdottir, Bispebjerg Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertrophic Cardiomyopathy	Other: Exercise training	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Will Elevated Left Ventricle Filling Pressures Decrease by a Group Exercise Program in Patients With Hypertrophic CardioMyopathy? - A Randomized Clinical Trial
• Actual Study Start Date: September 1, 2018
• Estimated Primary Completion Date: November 1, 2022
• Estimated Study Completion Date: November 1, 2022

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Usual activity level; 12 weeks of usual activity level
Active Comparator: Exercise training; 12 weeks of moderate intensity exercise training, 3 hours a week	Other: Exercise training; 12 weeks, 3 hours a week, moderate intensity exercise training

Outcome Measures

Primary Outcome Measures :

1. Change from baseline to follow-up in PCWP at 25 W [ Time Frame: 12 weeks ]
   Pulmonary capillary wedge pressure (mmHg)

Secondary Outcome Measures :

1. Pulmonary capillary wedge pressure [ Time Frame: 12 weeks ]
   At rest, at 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg)
2. Workload adjusted Pulmonary capillary wedge pressure [ Time Frame: 12 weeks ]
   At rest, at 25% and 50% of the maximum workload and at maximum workload, measured as mmHg/kg/W
3. Systemic vascular resistance [ Time Frame: 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)
4. Exercise capacity [ Time Frame: 12 weeks ]
   Measured as watt at maximum workload
5. Heart rate [ Time Frame: 12 weeks ]
   At rest, during exercise and at maximum exercise capacity (beats/min)
6. Blood pressure [ Time Frame: 12 weeks ]
   At rest, at maximum workload, 6 minutes after cease of workload (mmHg)
7. Cardiac index [ Time Frame: 12 weeks ]
   At rest, 25W and at maximum workload (L/min/m2):
8. Arterio-venous difference [ Time Frame: 12 weeks ]
   At rest, 25W and at maximum workload (ml O2/L)and workload corrected (mlO2/L/W)
9. VO2 max [ Time Frame: 12 weeks ]
   Measered as ml O2/min/kg
10. Quality of life questionnaire [ Time Frame: 12 weeks ]
    Measured by Kansas City Cardiomyopathy score
11. NT-Pro-BNP [ Time Frame: 12 weeks ]
    (pmol/L)
12. Troponin-T [ Time Frame: 12 weeks ]
    (mmol/L)
13. Echocardiographic parameters [ Time Frame: 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).

Other Outcome Measures:

1. Left ventricular fibrosis [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Helga L Gudmundsdottir, MD; 40632147 ext 0045; helgalilliang@gmail.com

Locations

Denmark

Rigshospitalet; Recruiting

Copenhagen, Denmark, 2100

Contact: Helga L Gudmundsdottir 40632147 helga.lillian.gudmundsdottir@regionh.dk

Sponsors and Collaborators

Bispebjerg Hospital

Rigshospitalet, Denmark

More Information

• Responsible Party: Helga Gudmundsdottir, MD, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT03537183
• Other Study ID Numbers: 63446
• First Posted: May 25, 2018
• Last Update Posted: March 3, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Helga Gudmundsdottir, Bispebjerg Hospital:

hypertrophic cardiomyopathy; exercise training; PCWP

Additional relevant MeSH terms:

Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases