Title

Pacemaker-induced transient asynchrony suppresses heart failure progression

UMMS Affiliation

Department of Cell and Developmental Biology

Publication Date

2015-12-23

Document Type

Article

Disciplines

Biophysics | Cardiology | Cardiovascular Diseases | Cell Biology

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 beta-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.

DOI of Published Version

10.1126/scitranslmed.aad2899

Source

Sci Transl Med. 2015 Dec 23;7(319):319ra207. doi: 10.1126/scitranslmed.aad2899. Link to article on publisher's site

Journal/Book/Conference Title

Science translational medicine

Comments

Full author list omitted for brevity. For full list of authors see article.

Related Resources

Link to Article in PubMed

PubMed ID

26702095

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