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Sci Transl Med. 2015 Dec 23;7(319):319ra207. doi: 10.1126/scitranslmed.aad2899.

Pacemaker-induced transient asynchrony suppresses heart failure progression.

Author information

1
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
3
St. Jude Medical, Sunnyvale, CA 94085, USA.
4
Advanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
5
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
6
Department of Cell and Molecular Physiology, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.
7
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Advanced Clinical Biosystems Research Institute, Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
8
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dkass@jhmi.edu.

Abstract

Uncoordinated contraction from electromechanical delay worsens heart failure pathophysiology and prognosis, but restoring coordination with biventricular pacing, known as cardiac resynchronization therapy (CRT), improves both. However, not every patient qualifies for CRT. We show that heart failure with synchronous contraction is improved by inducing dyssynchrony for 6 hours daily by right ventricular pacing using an intracardiac pacing device, in a process we call pacemaker-induced transient asynchrony (PITA). In dogs with heart failure induced by 6 weeks of atrial tachypacing, PITA (starting on week 3) suppressed progressive cardiac dilation as well as chamber and myocyte dysfunction. PITA enhanced β-adrenergic responsiveness in vivo and normalized it in myocytes. Myofilament calcium response declined in dogs with synchronous heart failure, which was accompanied by sarcomere disarray and generation of myofibers with severely reduced function, and these changes were absent in PITA-treated hearts. The benefits of PITA were not replicated when the same number of right ventricular paced beats was randomly distributed throughout the day, indicating that continuity of dyssynchrony exposure is necessary to trigger the beneficial biological response upon resynchronization. These results suggest that PITA could bring the benefits of CRT to the many heart failure patients with synchronous contraction who are not CRT candidates.

PMID:
26702095
PMCID:
PMC4858435
DOI:
10.1126/scitranslmed.aad2899
[Indexed for MEDLINE]
Free PMC Article

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