TAKO-TSUBO Cardiomyopathy and Genetic

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.

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.

Eligibility Criteria:
"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