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Mechanical dyssynchrony precedes QRS widening in ATP-sensitive K⁺ channel-deficient dilated cardiomyopathy


Yamada, Satsuki; Arrell, D Kent; Kane, Garvan C; Nelson, Timothy J; Perez-Terzic, Carmen M; Behfar, Atta; Purushothaman, Saranya; Prinzen, Frits W; Auricchio, Angelo; Terzic, Andre (2013). Mechanical dyssynchrony precedes QRS widening in ATP-sensitive K⁺ channel-deficient dilated cardiomyopathy. Journal of the American Heart Association, 2(6):e000410.

Abstract

BACKGROUND: Contractile discordance exacerbates cardiac dysfunction, aggravating heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would enable an early diagnosis before advanced disease.
METHODS AND RESULTS: High-resolution speckle-tracking echocardiography was applied in a knockout murine surrogate of adult-onset human cardiomyopathy caused by mutations in cardioprotective ATP-sensitive K(+) (K(ATP)) channels. Preceding the established criteria of cardiac dyssynchrony, multiparametric speckle-based strain resolved nascent erosion of dysfunctional regions within cardiomyopathic ventricles of the K(ATP) channel-null mutant exposed to hemodynamic stress. Not observed in wild-type counterparts, intraventricular disparity in wall motion, validated by the degree, direction, and delay of myocardial speckle patterns, unmasked the disease substrate from asymptomatic to overt heart failure. Mechanical dyssynchrony preceded widening of the QRS complex and exercise intolerance and progressed into global myocardial discoordination and decompensated cardiac pump function, precipitating a low output syndrome.
CONCLUSIONS: The present study, with the use of high-resolution imaging, prospectively resolved the origin and extent of intraventricular motion disparity in a K(ATP) channel-knockout model of dilated cardiomyopathy. Mechanical dyssynchrony established as an early marker of cardiomyopathic disease offers novel insight into the pathodynamics of dyssynchronous heart failure.

Abstract

BACKGROUND: Contractile discordance exacerbates cardiac dysfunction, aggravating heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would enable an early diagnosis before advanced disease.
METHODS AND RESULTS: High-resolution speckle-tracking echocardiography was applied in a knockout murine surrogate of adult-onset human cardiomyopathy caused by mutations in cardioprotective ATP-sensitive K(+) (K(ATP)) channels. Preceding the established criteria of cardiac dyssynchrony, multiparametric speckle-based strain resolved nascent erosion of dysfunctional regions within cardiomyopathic ventricles of the K(ATP) channel-null mutant exposed to hemodynamic stress. Not observed in wild-type counterparts, intraventricular disparity in wall motion, validated by the degree, direction, and delay of myocardial speckle patterns, unmasked the disease substrate from asymptomatic to overt heart failure. Mechanical dyssynchrony preceded widening of the QRS complex and exercise intolerance and progressed into global myocardial discoordination and decompensated cardiac pump function, precipitating a low output syndrome.
CONCLUSIONS: The present study, with the use of high-resolution imaging, prospectively resolved the origin and extent of intraventricular motion disparity in a K(ATP) channel-knockout model of dilated cardiomyopathy. Mechanical dyssynchrony established as an early marker of cardiomyopathic disease offers novel insight into the pathodynamics of dyssynchronous heart failure.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Cardiocentro Ticino
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:04 Feb 2014 09:55
Last Modified:05 Apr 2016 17:29
Publisher:Wiley Open Access
ISSN:2047-9980
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/JAHA.113.000410
PubMed ID:24308936

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