Assessment of Cardiac Function, Microvascular Function and Cardiac Perfusion in Different Disease Stages of Hypertrophic Cardiomyopathy (FUSION-HCM)

Assessment of Myocardial Function, (Peripheral) Endothelial Function and Perfusion in Early and Advanced Disease Stages of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by asymmetric hypertrophy of the heart in absence of loading conditions like hypertension. The genetic mutation underlying HCM sets in motion a cascade of functional and metabolic changes ultimately leading to disease. HCM patients often have microvascular dysfunction and myocardial perfusion deficits, of which the aetiology has not been elucidated. Whether these changes are secondary to remodelling or primarily caused by endothelial dysfunction is unclear. As the pathomechanism of HCM is thought to be a cascade of changes, it is important to gain more insight in the perfusion and endothelial function changes throughout different stages of disease: no phenotype, mild phenotype, and advanced HCM phenotype. In this study we aim to investigate these changes in the two most common genetic mutations.

Study Overview

• Status: Recruiting
• Conditions: Hypertrophic Cardiomyopathy; Hypertrophic Cardiomyopathy, Obstructive

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Julia E Visch, MD; Phone Number: +31629349699; Email: j.visch@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081HV
      • Recruiting
      • Amsterdam UMC - location VUMC
      • Contact: Julia E Visch, MD; Phone Number: +31629349699; Email: j.visch@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Potential study subjects are recruited from different hospitals and will be invited to the VUmc. Our research consortium consists of cardiologists and cardiogeneticists who will spread our call for participants to their patients. We will also work together with the HCM patient organization. Potential study subjects will be invited to contact us by phone or e-mail, after which an information letter will be sent. If someone is interested in participation in the study, they will be invited to the VUmc to sign informed consent and undergo day 1 of the study.

Description

Inclusion Criteria:

One of below:

• MYBPC3 mutation carrier
• MYH7 mutation carrier
• Genotype-negative first degree relative of a MYBPC3 or MYH7 mutation carrier

All of the following criteria:

• For the mutation carrier group: ≥18 years old
• For the genotype-negative group: ≥30 years old

MYBPC3 and MYH7 mutation carriers will be designated to one of three groups based on their maximum wall thickness, measured by echocardiography and MRI:

• No phenotype: MWT <12mm
• Mild Phenotype: MWT ≥12 until <15mm
• HCM phenotype: MWT ≥15mm

Exclusion Criteria:

• ≥70 years old
• Insulin-dependent diabetes mellitus
• Pregnancy
• Smoking
• Claustrophobia
• Pacemaker/ICD
• Renal insufficiency <30 GFR
• Hypertension (systolic >140mmHg or diastolic >90mmHg)
• For the genotype negative group, no phenotype group, and mild phenotype group: the use of blood pressure medication (diuretics, beta-blockers, ACE-inhibitors, angiotensin II receptor blockers, calcium channel blockers, alpha blockers)
• For the HCM phenotype group: when it is unsafe to withhold from blood pressure medication (as specified above) for two days, as assessed by their own cardiologist
• Left ventricular outflow tract gradient > 50mmHg
• Aortic valve disease
• Left bundle branch block
• (History of) Obstructive coronary artery disease
• Chronic atrial fibrillation
• Hormone replacement therapy
• Second or third-degree AV-block, sick-sinussyndrome, prolonged QT-interval
• Asthma and other obstructive pulmonary diseases
• Previous adverse reaction to adenosine or dotarem

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy controls
Mutation carriers
Mild hypertrophy
Overt hypertrophy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
myocardial blood flow	assessed by PET and CMR	1 month
peripheral endothelial function	assessed by EndoPAT and LASCA	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue characterization	assessed by CMR	1 month
Diastolic dysfunction	assessed by echocardiography	1 month
Fibrosis	assessed by CMR	1 month

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: endothelial function; perfusion; hypertrophic cardiomyopathy
• 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: NL83573.018.23

Drug and device information, study documents

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