1) To demonstrate an elevated troponin concentration before exercise and a rise of troponin after exercise in both pre-clinical HCM mutation carriers and HCM patients with the hypertrophic phenotype, 2) To evaluate the troponin rise in relation to…
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Source
Brief title
Condition
- Myocardial disorders
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients (pre-clinical HCM mutation carriers and clinical HCM
patients) with 1) a baseline troponin concentration above the upper reference
limit (the 99th percentile) of the high-sensitivity troponin assay that will be
used, and 2) a troponin rise after exercise testing (more than or equal to 20%
of the baseline concentration) using the same high sensitivity-troponin assay.
Secondary outcome
Pre-clinical HCM-group (genotype positive, no hypertrophy)
-The correlation between troponin (baseline concentration, rise after
exercise) and MRI parameters (i.e. myocardial mass and function, number of
segments with and volume (in mL) of LGE, presence of edema);
-The correlation between troponin ( baseline, rise after exercise) and
clinical follow-up (development of the hypertrophic phenotype, septum wall
thickness >13mm).
Clinical HCM group (genotype positive or negative, with hypertrophy)
-The correlation between troponin ( baseline concentration, rise after
exercise) and MRI parameters (i.e. myocardial mass and function, number of
segments with and volume (in mL) of LGE, presence of edema);
-The correlation between troponin (baseline concentration, rise after exercise)
and: a) death due to all causes, cardiovascular death, and sudden cardiac death
at two and 5 year follow-up; b) admission to the hospital for cardiac reasons
(i.e. new episode of heart failure, arrhythmia, syncope) during two and five
year follow-up; c) event free survival at two and 5 year, defined as alive at
the time of telephone call and not admitted for any cardiac adverse event
during follow-up.
Background summary
Hypertrophic cardiomyopathy (HCM) is the most common inheritable heart disease,
characterized by marked left ventricular hypertrophy (LVH) in the absence of a
disease that can cause hypertrophy to such extent. The clinical course in
patients with a full-blown hypertrophic phenotype is very heterogeneous,
ranging from early sudden cardiac death to late onset heart failure. Current
risk stratification to predict the outcome of individual HCM patients is still
unsatisfactory. From studies on gene carriers with a proven causal mutation but
without the hypertrophic phenotype, we know that the hypertrophy and subsequent
clinical course may develop later in life. The pathophysiology of both the
onset of hypertrophy in gene carriers and the development of disease in
clinical HCM patients with hypertrophic hearts is incompletely understood. It
is however recognized that ischemia plays a significant role. Interestingly,
although playing an important role in ischemic heart disease cardiac troponin
has received little attention in HCM patients. Against this background, we will
study the release of cardiac troponin after stress testing in 1) mutation
carriers without the hypertrophic phenotype (pre-clinical HCM) and in 2)
patients with clinically overt HCM (clinical HCM).
Study objective
1) To demonstrate an elevated troponin concentration before exercise and a rise
of troponin after exercise in both pre-clinical HCM mutation carriers and HCM
patients with the hypertrophic phenotype, 2) To evaluate the troponin rise in
relation to phenotypic characteristics, 3) To study the correlation between a
troponin rise and development of hypertrophy in pre-clinical mutation carriers
and the association between adverse cardiac events at two and 5-year follow-up.
Study design
All eligible subjects either mutation carriers without hypertrophy or clinical
HCM patients with hypertrophic hearts will undergo a baseline MRI, a bicycle
exercise test and blood sampling to assess serum troponin levels. Six and 24
hours after the exercise test repeat blood samples will be drawn. Troponin rise
of more than or equal to 20% will be called significant. Telephone follow-up
will occur on day 730 (+ 7 days) and on day 1826 (+ 35 days). A troponin rise
will be associated with the presence and extent of fibrosis and edema of the
heart as assessed with MRI. In mutation carriers the development of the
hypertrophic phenotype will be checked during follow-up. In patients with
clinical HCM clinical endpoints such as sudden cardiac death, new episodes of
heart failure and rhythm disturbances will be scored. The exercise induced
troponin rise will be analysed in multivariable analysis to assess its
association with the abovementioned outcome parameters.
Study burden and risks
Participants will have to pay 3 visits to the hospital at baseline and will be
followed-up by telephone call after two and five years. The risks are limited
to a potential allergic reaction to the MRI contrast agent Gadolinium (0-1%)
and in highly rare instances nephrogenic systemic fibrosis (NSF) may develop
(see references 80-82 in the study protocol). The MRI investigation in the
present study is regarded safe in the HCM population we will study, bearing in
mind the in- and exclusion criteria (i.e. patients with impaired renal function
defined as a glomerular filtration rate below 30 mL/min/m2 will be excluded).
The same is true for undergoing an exercise test, which in general is regarded
as a safe test in HCM patients. Only in patients with HCM and a severe
obstruction of the left ventricular outflow tract an exercise test may pose a
risk. Therefore, these participants will be excluded.
Participation will take time and effort. To partly compensate for this,
participants will receive reimbursements for travelling costs.
Participants will have no direct benefit. Hopefully our findings will enhance
our knowledge and improve risk stratification in these patients in the future.
Ziekerstraat 12D
6511LH Nijmegen
NL
Ziekerstraat 12D
6511LH Nijmegen
NL
Listed location countries
Age
Inclusion criteria
•Patients with an echocardiographically proven hypertrophic cardiomyopathy according to the ESC guidelines;
•Individuals with a HCM associated mutation without the clinical characteristics of hypertrophic cardiomyopathy (pre-clinical HCM patients);
•Age >= 18 years;
•Able to comply with the protocol;
•Written informed consent.
Exclusion criteria
•Known significant epicardial coronary artery disease;
•Patients with LVH in the clinical setting of other disorders that explain the myocardial hypertrophy (amyloidosis, MELAS, Anderson-Fabry, WPW etc.);
•Heart failure NYHA class III-IV;
•Patients with known hemodynamic instability or syncope during exercise due to left ventricular
outflow gradient or occurrence of ventricular arrhythmia;
•History of PTSMA (percutaneous transluminal septal myocardial ablation) or Morrow myectomy;
•Patients not able to complete a bicycle test;
•Any contraindication to MR imaging (MR imaging is not obligatory for assessment of the primary objective, therefore relative exclusion criterion);
•Recent (within 30 days) admittance to the hospital for any cardiac reason (myocardial infarction, heart failure, cardiac arrhythmia, etc.);
•Severe renal insufficiency (eGFR < 30 ml/min);
•Any other condition which, in the opinion of the investigator, may pose a significant hazard to the subject if he or she participates in the present study.
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 | NL37776.091.11 |