TAKO-TSUBO Cardiomyopathy and Genetic

Acute Coronary Syndrome Clinical Trial

Official title:

Genetic Polymorphisms in Catecholamine Pathway Responsible for the Tako-TSUBO Cardiomyopathy Susceptibly (TAKO-GENE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01520610
• Other study ID #: AOR 10018
• Status: Completed
• Phase: N/A
• First received: December 23, 2011
• Last updated: September 14, 2016
• Start date: November 2011
• Est. completion date: May 2016

Study information

• Verified date: February 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

This is a case-control association study with multicentric prospective recruitment.

Tako-TSUBO cardiomyopathy is a new clinical entity mimicking an acute coronary syndrome. It is characterized by reversible left ventricular dysfunction that is frequently precipitated by a stressful event and most of patients are postmenopausal women.

Several hypotheses concerning pathogenesis of Tako-TSUBO cardiomyopathy have been proposed, but at present, exaggerated sympathetic stimulation is the main hypothesis. However, the investigators don't know why some patients with stressful event may present Tako-TSUBO cardiomyopathy whereas most of them don't.

The investigators hypothesize that polymorphisms in the genes involved in the adrenergic pathway resulting in greater catecholamine sensitivity would be associated with an increased risk of Tako-TSUBO cardiomyopathy.

Description:

We hypothesize that polymorphisms in the genes involved in the adrenergic pathway resulting in greater catecholamine sensitivity would be associated with an increased risk of Tako-TSUBO cardiomyopathy.

Aim of this study:

Primary endpoint: Cognitive study aiming at identifying genetic polymorphisms in adrenergic pathway responsible for the Tako-TSUBO cardiomyopathy susceptibly.

Secondary endpoint: Study of clinical, ECG, angiographic, echocardiographic characteristics and outcome of patients presenting with Tako-TSUBO cardiomyopathy.

Methods:

Case-control association study with multicentric prospective recruitment. The study population will be consisted of 800 Caucasians subjects: 200 patients with Tako-TSUBO cardiomyopathy and an age- and sex-matched control group (n = 600) of 400 patients with acute coronary syndrome and 200 patients with stressful event (emergency postoperative patients) but without Tako-TSUBO cardiomyopathy. Sixteen candidates genes from the catecholamine pathway will be studied.

The diagnosis of Tako-TSUBO cardiomyopathy will be defined as (1) an acute chest pain during a stressful incident associated with ST-segment abnormalities and/or increased serum troponin level, (2) transient left ventricular systolic dysfunction, and (3) no coronary lesions related to the left ventricular dysfunction.

Diagnosis of acute coronary syndrome will be performed according to the definition of the American Heart Association/American College of Cardiology and European Society of Cardiology.

We will genotype all the known functional SNPs (Single Nucleotide Polymorphisms) and the Tag SNPs representative of at least 80% of the total genetic diversity (available at HapMap web site). SNPs will be studied alone or combined in haplotype.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 530
• Est. completion date: May 2016
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

"Tako-TSUBO" group:

Inclusion criteria :

• Patients presenting with Tako-TSUBO cardiomyopathy defined as: 1) an acute chest pain during a stressful incident associated with ST-segment abnormalities and/or increased serum troponin level, 2) transient left ventricular systolic dysfunction, and 3) no coronary lesions related to the left ventricular dysfunction

• Age > 18

• Written consent

• Caucasian origin

• Affiliation to health care system

Exclusion criteria :

• Patients presenting with pheochromocytoma

• Patients presenting with myocarditis

• Patients presenting with subarachnoid hemorrhage

"Acute coronary syndrome" group (age- and sex-matched control group):

Inclusion criteria :

• Patients presenting with an acute coronary syndrome (according to the definitions of guidelines)

• Age > 18

• written consent

• Caucasian origin

• Affiliation to health care system

Exclusion criteria :

• Patients presenting with a suspicion of Tako-TSUBO cardiomyopathy

• Patients presenting with a history of Tako-TSUBO cardiomyopathy

"Surgical stress" group (age- and sex-matched control group):

Inclusion criteria :

• Patients hospitalized for an urgent surgery

• Age > 18

• Written consent

• Caucasian origin

• Affiliation to health care system

Exclusion criteria :

• Patients presenting with increase of troponin after surgery

• Patients presenting with ECG abnormalities after surgery

• Patients presenting with a suspicion of Tako-TSUBO cardiomyopathy

• Patients presenting with a history of Tako-TSUBO cardiomyopathy

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Cardiomyopathies
• Tako-TSUBO Cardiomyopathy
• Takotsubo Cardiomyopathy

Locations

Country	Name	City	State
France	Name: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré. Université de Versailles-Saint Quentin en Yvelines	Boulogne Billancourt	Hautes des Seine

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fédération Française de Cardiologie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA analysis	To identify genetic polymorphisms in adrenergic pathway responsible for the Tako-TSUBO cardiomyopathy susceptibly	48 months	No
Secondary	Diagnosis and prognosis of Tako-TSUBO cardiomyopathy	To assess diagnostic criteria of Tako-TSUBO cardiomyopathy To assess the prognosis of Tako-TSUBO cardiomyopathy	48 months	No