title: Mechanical dyssynchrony precedes QRS widening in ATP-sensitive K⁺ channel-deficient dilated cardiomyopathy.
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.
  
  
  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.
authors.affiliation: Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Yamada
authors.forename: D Kent
authors.initials: DK
authors.lastname: Arrell
authors.forename: Garvan C
authors.initials: GC
authors.lastname: Kane
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Perez-Terzic
authors.forename: Atta
authors.initials: A
authors.lastname: Behfar
authors.forename: Saranya
authors.initials: S
authors.lastname: Purushothaman
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.forename: Angelo
authors.initials: A
authors.lastname: Auricchio
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D015150:Echocardiography, Doppler; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D054086:KATP Channels / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D000099161:Kcnj11 Channel
chemical_list: D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel
keywords: ATP‐sensitive K+ channel; Kir6.2; QRS complex; heart failure; speckle‐tracking