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Editorial
. 2014 Aug;14(8):1055-60.
doi: 10.1517/14712598.2014.922536. Epub 2014 May 19.

Reparative resynchronization in ischemic heart failure: an emerging strategy

Satsuki Yamada  1 , Andre Terzic
Affiliations
Editorial

Reparative resynchronization in ischemic heart failure: an emerging strategy

Satsuki Yamada et al. Expert Opin Biol Ther. 2014 Aug.

Abstract

Cardiac dyssynchrony refers to disparity in cardiac wall motion, a serious consequence of myocardial infarction associated with poor outcome. Infarct-induced scar is refractory to device-based cardiac resynchronization therapy, which relies on viable tissue. Leveraging the prospect of structural and functional regeneration, reparative resynchronization has emerged as a potentially achievable strategy. In proof-of-concept studies, stem-cell therapy eliminates contractile deficit originating from infarcted regions and secures long-term synchronization with tissue repair. Limited clinical experience suggests benefit of cell interventions in acute and chronic ischemic heart disease as adjuvant to standard of care. A regenerative resynchronization option for dyssynchronous heart failure thus merits validation.

Keywords: biologics; cardiac resynchronization therapy; clinical trial; dyssynchrony; heart failure; myocardial infarction; regenerative medicine; stem cells.

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Figures

Figure 1.
Figure 1.
Stem-cell intervention rescues disparity in ventricular wall motion post-infarction. Impact of stem-cell biotherapy on cardiac dyssynchrony deconvoluted in a murine infarction model. A total dose of 200,000 undifferentiated induced pluripotent stem (iPS) cells per heart (40,000 cells/site × 5 sites) was delivered by epicardial route into the peri-infarcted anterior wall of the left ventricle within 30 min following coronary ligation. Pre-infarction, all segments of the left ventricle demonstrate harmonious contraction during systole (left top) and relaxation during diastole (left middle) documented by in vivo speckle-tracking echocardiography. At 1 month, infarction precipitated dyssynchronous motion characterized by early stretch followed by delayed contraction (middle) with correction afforded by iPS cell therapy (right). Bottom row depicts fitted strain patterns reflecting normokinesis pre-infarction (left), dyssynchrony post-infarction without treatment (middle), and resynchronization following cell therapy (right). See also Ref. .
Figure 2.
Figure 2.
Stem-cell–based resynchronization complements standard of care. Dyssynchronous heart failure is a malignant disorder commonly refractory to the existing therapeutic armamentarium that currently combines pharmacotherapy with device-based resynchronization. Responsiveness to pacing devices is impeded by the scar burden post-infarction, mandating approaches capable to promote tissue repair. Potential applications of stem-cell–based reparative resynchronization include cardioprotection in acute/subacute phases of disease to prevent disease progression, and normative restitution to restore structure and function in the setting of chronic dyssynchronous heart failure.
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