To determine whether a standardized exercise workload elicits a different response on 1) metabolites/cardiac biomarkers in the general circulation (measured by blood values), and 2) contraction patterns in local myocardium (measured by…
ID
Source
Brief title
Condition
- Myocardial disorders
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
There will be two main study parameters: 1) blood metabolite/biomarker levels
(e.g. fatty acids, ketones, troponin and nt-proBNP); and 2) echocardiographic
parameters (e.g. right ventricular dimension/function and systolic right
ventricular pressure, as well as deformation patterns).
As a primary analysis, the main study parameters will be univariably compared
between affected ACM patients and controls.
Secondary outcome
Secondary study parameters include the occurrence of VA during the exercise
test (defined as (non-) sustained ventricular tachycardia, ventricular
fibrillation, or appropriate intervention from an implantable
cardioverter-defibrillator).
As a secondary analysis, the main study parameters will be compared between
preclinical ACM mutation carriers and controls, and the main study parameters
will be associated with the occurrence of VAs.
Background summary
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease that
is associated with a risk of potentially life-threatening ventricular
arrhythmias (VAs). The disease is caused by pathogenic DNA variants
(*mutations*). Remarkably, the majority of VAs in ACM patients occur during
exercise, and exercise increases penetrance among ACM-associated pathogenic
mutation carriers. While this suggests that exercise is an environmental
modifier of ACM, evidence that explains the interaction between exercise and
ACM expression is lacking. We hypothesize that patients with ACM have impaired
metabolic function, which makes them susceptible to disease development upon
exercise.
Study objective
To determine whether a standardized exercise workload elicits a different
response on 1) metabolites/cardiac biomarkers in the general circulation
(measured by blood values), and 2) contraction patterns in local myocardium
(measured by echocardiography) between affected ACM patients and healthy
controls. As a secondary objective, we aim to determine whether similar
differences can be observed in unaffected ACM mutation carriers versus
controls, and whether these metabolic changes are related to VA occurrence.
Study design
Cross-sectional single-center observational case-control study.
Study burden and risks
Affected and preclinical ACM mutation carriers routinely undergo exercise
testing and echocardiography as part of their annual ACM workup. This study
adds non-invasive breath-gas analysis, two blood draws and an overnight fast.
These procedures are thought to have a negligible risk to the patient, while
the potential benefit of understanding the role of exercise in ACM pathogenesis
is large.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
Affected ACM patients:
- Carrier of a (likely) pathogenic PKP2 variant (i.e. class 4 or 5 variant as
per American College of Medical Genetics guidelines).
- Fulfillment of definite ACM diagnosis as per 2010 Task Force Criteria.
- Written informed consent.
Preclinical ACM mutation carriers:
- Carrier of a (likely) pathogenic PKP2 variant (i.e. class 4 or 5 variant as
per American College of Medical Genetics guidelines).
- No fulfillment of definite ACM diagnosis as per 2010 Task Force Criteria.
- Written informed consent.
Healthy controls:
- No prior history of cardiac complaints.
- Normal echocardiogram.
- Normal ECG.
- Written informed consent.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
Affected and preclinical ACM mutation carriers:
- Not carrying a (likely) pathogenic PKP2 variant (i.e. class 4 or 5 variant as
per American College of Medical Genetics guidelines).
- Prior life-threatening arrhythmia during exercise (including sudden cardiac
arrest, ventricular fibrillation, sustained ventricular tachycardia,
appropriate implantable cardioverter-defibrillator intervention)
- Unwilling or unable to provide written informed consent
Healthy controls:
- Prior history of cardiac complaints
- Abnormal echocardiogram
- Abnormal ECG
- Unwilling or unable to provide written informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84335.041.23 |