• Satsuki Yamada, D Kent Arrell, Almudena Martinez-Fernandez, Atta Behfar, Garvan C Kane, Carmen M Perez-Terzic, Ruben J Crespo-Diaz, Robert J McDonald, Saranya P Wyles, Jelena Zlatkovic-Lindor, Timothy J Nelson, and Andre Terzic.
• Center for Regenerative Medicine, Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, MN (S.Y., K.A., A.M.F., A.B., G.C.K., C.M.P.T., R.J.C.D., R.J.M.D., S.P.W., J.Z.L., T.J.N., A.T.).
• J Am Heart Assoc. 2015 May 1;4(5).

BackgroundCardiac 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 ResultsProgressive 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.ConclusionsIn narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device-autonomous resynchronization therapy for refractory disease.© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

42 keywords...

hide…