Skip to main content

Pacemaker-induced transient asynchrony suppresses heart failure progression.

Publication ,  Journal Article
Kirk, JA; Chakir, K; Lee, KH; Karst, E; Holewinski, RJ; Pironti, G; Tunin, RS; Pozios, I; Abraham, TP; de Tombe, P; Rockman, HA; Van Eyk, JE ...
Published in: Sci Transl Med
December 23, 2015

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 23, 2015

Volume

7

Issue

319

Start / End Page

319ra207

Location

United States

Related Subject Headings

  • Sarcomeres
  • Receptors, Adrenergic, beta
  • Proteomics
  • Pacemaker, Artificial
  • Myofibrils
  • Myocytes, Cardiac
  • Heart Failure
  • Dogs
  • Disease Progression
  • Calcium
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kirk, J. A., Chakir, K., Lee, K. H., Karst, E., Holewinski, R. J., Pironti, G., … Kass, D. A. (2015). Pacemaker-induced transient asynchrony suppresses heart failure progression. Sci Transl Med, 7(319), 319ra207. https://doi.org/10.1126/scitranslmed.aad2899
Kirk, Jonathan A., Khalid Chakir, Kyoung Hwan Lee, Edward Karst, Ronald J. Holewinski, Gianluigi Pironti, Richard S. Tunin, et al. “Pacemaker-induced transient asynchrony suppresses heart failure progression.Sci Transl Med 7, no. 319 (December 23, 2015): 319ra207. https://doi.org/10.1126/scitranslmed.aad2899.
Kirk JA, Chakir K, Lee KH, Karst E, Holewinski RJ, Pironti G, et al. Pacemaker-induced transient asynchrony suppresses heart failure progression. Sci Transl Med. 2015 Dec 23;7(319):319ra207.
Kirk, Jonathan A., et al. “Pacemaker-induced transient asynchrony suppresses heart failure progression.Sci Transl Med, vol. 7, no. 319, Dec. 2015, p. 319ra207. Pubmed, doi:10.1126/scitranslmed.aad2899.
Kirk JA, Chakir K, Lee KH, Karst E, Holewinski RJ, Pironti G, Tunin RS, Pozios I, Abraham TP, de Tombe P, Rockman HA, Van Eyk JE, Craig R, Farazi TG, Kass DA. Pacemaker-induced transient asynchrony suppresses heart failure progression. Sci Transl Med. 2015 Dec 23;7(319):319ra207.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 23, 2015

Volume

7

Issue

319

Start / End Page

319ra207

Location

United States

Related Subject Headings

  • Sarcomeres
  • Receptors, Adrenergic, beta
  • Proteomics
  • Pacemaker, Artificial
  • Myofibrils
  • Myocytes, Cardiac
  • Heart Failure
  • Dogs
  • Disease Progression
  • Calcium