Clinical trial NCT02520856: New Diagnostic Strategy in Hypertrophic Cardiomyopathy
Official title: New Diagnostic Strategy in Hypertrophic Cardiomyopathy Including a New Genetic Approach: A Multicentric Prospective Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypertrophic Cardiomyopathy
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2015-08-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients with unexplained Hypertrophic cardiomyopathy will be prospectively included.

HCM diagnosis will be based on conventional echocardiographic criteria and will be considered definite in the presence of LV hypertrophy without cavity dilatation and without other cardiac or systemic disease able to produce the magnitude of hypertrophy.

Brief summary: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by unexplained hypertrophy of the left ventricle, often with predominant involvement of the interventricular septum, and characterized by myocyte disarray and fibrosis.

HCM is the most common familial heart disease with strong genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of the cardiac sarcomere are responsible for (or associated with) HCM.

However, 30-40% of sporadic and familial cases of HCM are still genetically unlabelled. In addition, secondary HCM caused by Fabry's disease or amyloidosis, may mimic primary HCM and may be under diagnosed. This may result in a delay in accurate diagnosis and instauration of specific treatment, with possible clinical consequences for the patients.

For these reasons, we decided to apply a new diagnostic strategy for patients with newly diagnosed HCM, including the whole exome sequencing (WES) technology.

If correctly applied, this new technology has the potential to strongly reduce the diagnostic wavering leading to earlier diagnosis and genetic counseling in sarcomeric HCM and rarer forms of secondary HCM including Fabry's disease and amyloidosis, and also specific therapy set-up in secondary forms of HCM. It should also allow identifying new genes responsible for HCM.

Detailed description: Background : Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by unexplained hypertrophy of the left ventricle, often with predominant involvement of the interventricular septum, and characterized by myocyte disarray and fibrosis.

HCM is the most common familial heart disease with strong genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of the cardiac sarcomere are responsible for (or associated with) HCM.

However, 30-40% of sporadic and familial cases of HCM are still genetically unlabelled. In addition, secondary HCM caused by Fabry's disease or amyloidosis, may mimic primary HCM and may be under diagnosed. This may result in a delay in accurate diagnosis and instauration of specific treatment, with possible clinical consequences for the patients.

Objectives : For these reasons, we decided to apply a new diagnostic strategy for patients with newly diagnosed HCM, including the whole exome sequencing (WES) technology.

1. Main objective: to evaluate the additional diagnostic value of the new proposed strategy for the identification of a specific cause of HCM as compared with conventional diagnostic strategy
2. Secondary objectives:

To evaluate the frequency of secondary HCM (Fabry's disease, amyloidosis, mitochondrial cardiomyopathies, and others) observed by this systematic screening in a population of newly diagnosed HCM

Perspectives: If correctly applied, this new technology has the potential to strongly reduce the diagnostic wavering leading to earlier diagnosis and genetic counseling in sarcomeric HCM and rarer forms of secondary HCM including Fabry's disease and amyloidosis, and also specific therapy set-up in secondary forms of HCM. It should also allow identifying new genes responsible for HCM.

Eligibility criteria: Inclusion Criteria:

* patient with newly diagnosed hypertrophic cardiomyopathy (HCM), based on conventional echocardiographic criteria.The diagnosis of HCM will be considered definite in the presence of left ventricle hypertrophy without cavity dilatation and without other cardiac or systemic disease able to produce the magnitude of hypertrophy.

Exclusion Criteria:

* Associated cardiac or non cardiac disease known to cause left ventricle hypertrophy (uncontrolled systemic Hypertension, severe aortic stenosis)

Primary outcomes:
measure: whole exome sequencing
timeFrame: 12 months
measure: Classic genetic analysis
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille
Study officials:
affiliation: Assistance Publique Hôpitaux de Marseille
name: Urielle DESALBRES
role: STUDY_DIRECTOR
References: