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ABSTRACT: Background
Cardiac resynchronization therapy using bi-ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS-complex. In the absence of QRS prolongation, however, device-based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell-based approach in the setting of narrow QRS-complex HF.Methods and results
Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of stress-triggered dilated cardiomyopathy. In contrast to rampant end-stage disease afflicting untreated cohorts, stem cell intervention early in disease, characterized by mechanical dyssynchrony and a narrow QRS-complex, aborted progressive dyssynchronous HF and prevented QRS widening. Stem cell-treated hearts acquired coordinated ventricular contraction and relaxation supporting systolic and diastolic performance. Rescue of contractile dynamics was underpinned by a halted left ventricular dilatation, limited hypertrophy, and reduced fibrosis. Reverse remodeling reflected a restored cardiomyopathic proteome, enforced at systems level through correction of the pathological molecular landscape and nullified adverse cardiac outcomes. Cell therapy of a dyssynchrony-prone cardiomyopathic cohort translated prospectively into improved exercise capacity and prolonged survivorship.Conclusions
In narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device-autonomous resynchronization therapy for refractory disease.
SUBMITTER: Yamada S
PROVIDER: S-EPMC4599402 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Yamada Satsuki S Arrell D Kent DK Martinez-Fernandez Almudena A Behfar Atta A Kane Garvan C GC Perez-Terzic Carmen M CM Crespo-Diaz Ruben J RJ McDonald Robert J RJ Wyles Saranya P SP Zlatkovic-Lindor Jelena J Nelson Timothy J TJ Terzic Andre A
Journal of the American Heart Association 20150511 5
<h4>Background</h4>Cardiac resynchronization therapy using bi-ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS-complex. In the absence of QRS prolongation, however, device-based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell-based approach in the setting of narrow QRS-complex HF.<h4>Methods and results</h4>Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of stress-tr ...[more]