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

Satsuki Yamada, D. Kent Arrell, Almudena Martinez-Fernandez, Atta Behfar, Garvan M Kane, Carmen M Terzic, Ruben J. Crespo-Diaz, Robert McDonald, Saranya P. Wyles, Jelena Zlatkovic-Lindor, Timothy J Nelson, Andre Terzic

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume4
Issue number5
DOIs
StatePublished - May 11 2015

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Cardiomyopathies
Heart Failure
Stem Cells
Equipment and Supplies
Cardiac Resynchronization Therapy
Dilated Cardiomyopathy
Proteome
Therapeutics
Cell- and Tissue-Based Therapy
Hypertrophy
Dilatation
Fibrosis

Keywords

  • mechanical discordance
  • proteome
  • resynchronization
  • speckle‐tracking
  • stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy. / Yamada, Satsuki; Arrell, D. Kent; Martinez-Fernandez, Almudena; Behfar, Atta; Kane, Garvan M; Terzic, Carmen M; Crespo-Diaz, Ruben J.; McDonald, Robert; Wyles, Saranya P.; Zlatkovic-Lindor, Jelena; Nelson, Timothy J; Terzic, Andre.

In: Journal of the American Heart Association, Vol. 4, No. 5, 11.05.2015.

Research output: Contribution to journalArticle

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