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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertrophic Cardiomyopathy
• Intervention / Treatment: Other: Exercise training

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Helga L Gudmundsdottir, MD; Phone Number: 0045 40632147; Email: helgalilliang@gmail.com

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to follow-up in PCWP at 25 W	Pulmonary capillary wedge pressure (mmHg)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary capillary wedge pressure	At rest, at 25% and 50% of the maximum workload and at maximum workload ( measured as mmHg)	12 weeks
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
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
Exercise capacity	Measured as watt at maximum workload	12 weeks
Heart rate	At rest, during exercise and at maximum exercise capacity (beats/min)	12 weeks
Blood pressure	At rest, at maximum workload, 6 minutes after cease of workload (mmHg)	12 weeks
Cardiac index	At rest, 25W and at maximum workload (L/min/m2):	12 weeks
Arterio-venous difference	At rest, 25W and at maximum workload (ml O2/L)and workload corrected (mlO2/L/W)	12 weeks
VO2 max	Measered as ml O2/min/kg	12 weeks
Quality of life questionnaire	Measured by Kansas City Cardiomyopathy score	12 weeks
NT-Pro-BNP	(pmol/L)	12 weeks
Troponin-T	(mmol/L)	12 weeks
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): April 1, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: May 9, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: exercise training; hypertrophic cardiomyopathy; PCWP
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 63446

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No