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Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience.

ABSTRACT: BACKGROUND: Some patients with Takotsubo cardiomyopathy (TTC) develop cardiogenic shock due to left ventricular outflow tract (LVOT) obstruction - there is, however, a paucity of data regarding this condition. METHODS: Prevalence, associated factors and management implications of LVOT obstruction in TTC was explored, based on two-year data from two Belgian heart centres. RESULTS: A total of 32 patients with TTC were identified out of 3,272 patients presenting with troponin-positive acute coronary syndrome. In six patients diagnosed with TTC (19%), a significant LVOT obstruction was detected by transthoracic echocardiography. Patients with LVOT obstruction were older and had more often septal bulging, and presented more frequently in cardiogenic shock as compared to those without LVOT obstruction (P < 0.05). Moreover, all patients with LVOT obstruction showed systolic anterior motion (SAM) of the anterior mitral valve leaflet, which was associated with a higher grade of mitral regurgitation (2.2±0.7 vs. 1.0±0.6, P<0.001). Adequate therapeutic management including fluid resuscitation, cessation of inotropic therapy, intravenous ?-blocker, and the use of intra-aortic balloon pump resulted in non-inferior survival in TTC patients with LVOT obstruction as compared to those without LVOT obstruction. CONCLUSIONS: TTC is complicated by LVOT obstruction in approximately 20% of cases. Older age, septal bulging, SAM-induced mitral regurgitation and hemodynamic instability are associated with this condition. Timely and accurate diagnosis of LVOT obstruction by echocardiography is key to successful management of these TTC patients with LVOT obstruction and results in a non-inferior outcome as compared to those patients without LVOT obstruction.

SUBMITTER: De Backer O

PROVIDER: S-EPMC4210484 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience.

De Backer Ole O Debonnaire Philippe P Gevaert Sofie S Missault Luc L Gheeraert Peter P Muyldermans Luc L

BMC cardiovascular disorders 20141022

<h4>Background</h4>Some patients with Takotsubo cardiomyopathy (TTC) develop cardiogenic shock due to left ventricular outflow tract (LVOT) obstruction - there is, however, a paucity of data regarding this condition.<h4>Methods</h4>Prevalence, associated factors and management implications of LVOT obstruction in TTC was explored, based on two-year data from two Belgian heart centres.<h4>Results</h4>A total of 32 patients with TTC were identified out of 3,272 patients presenting with troponin-pos ...[more]

PMID: 25339604

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Project description:Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.

Dataset Information

Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience.

Publications

Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience.

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