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Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy.


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

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Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy.

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]

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