New Diagnostic Strategy in Hypertrophic Cardiomyopathy (HYPERGEN)

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

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.

Study Overview

• Status: Unknown
• Conditions: Hypertrophic Cardiomyopathy
• Intervention / Treatment: Other: blood sample

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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Gilbert HABIB, Professor; Email: gilbert.habib@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypertrophic cardiomyopathy; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: August 5, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 7, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 2014-29; RCAPHM14_0358 (Registry Identifier: Assistance Publique Hôpitaux de Marseille)