Clinical trial NCT06400524: Assessment of Cardiac Function, Microvascular Function and Cardiac Perfusion in Different Disease Stages of Hypertrophic Cardiomyopathy
Official title: Assessment of Myocardial Function, (Peripheral) Endothelial Function and Perfusion in Early and Advanced Disease Stages of Hypertrophic Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy, Obstructive
Keywords: hypertrophic cardiomyopathy
perfusion
endothelial function
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2024-05-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: myocardial blood flow
timeFrame: 1 month
measure: peripheral endothelial function
timeFrame: 1 month
Secondary outcomes:
measure: Tissue characterization
timeFrame: 1 month
measure: Diastolic dysfunction
timeFrame: 1 month
measure: Fibrosis
timeFrame: 1 month
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - location VUmc
state: Noord-Holland
Study officials:
References: