New Diagnostic Strategy in Hypertrophic Cardiomyopathy

Study Overview
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Brief Summary
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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
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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. 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 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.

Official Title
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New Diagnostic Strategy in Hypertrophic Cardiomyopathy Including a New Genetic Approach: A Multicentric Prospective Study

Conditions
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Hypertrophic Cardiomyopathy

Intervention / Treatment
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* Other: blood sample


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertrophic cardiomyopathy<br>All patients with newly diagnosed unexplained HCM will be prospectively included. All patients will undergo both classical genetic analysis and WES technology. | Other: blood sample<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| whole exome sequencing |  | 12 months | 
| Classic genetic analysis |  | 12 months |