Pacemaker-induced transient asynchrony suppresses heart failure progression
Jonathan A Kirk1, Khalid Chakir1, Kyoung Hwan Lee2
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Insights
Pacemaker-induced transient asynchrony (PITA) improves heart failure by temporarily inducing dyssynchrony, offering a new therapy for patients ineligible for cardiac resynchronization therapy (CRT). This novel approach benefits hearts with synchronous contractions, unlike traditional CRT.
Area of Science:
- Cardiology
- Biomedical Engineering
- Heart Failure Pathophysiology
Background:
- Uncoordinated heart contractions (electromechanical delay) worsen heart failure. Cardiac resynchronization therapy (CRT) improves heart failure by coordinating contractions but isn't suitable for all patients.
- Heart failure can present with synchronous contractions, a condition not currently addressed by CRT.
Purpose of the Study:
- To investigate the efficacy of pacemaker-induced transient asynchrony (PITA) in improving heart failure with synchronous contractions.
- To determine if PITA can offer an alternative therapeutic strategy for heart failure patients ineligible for CRT.
Main Methods:
- A canine model of heart failure was established using atrial tachypacing.
- PITA was implemented by daily 6-hour right ventricular pacing in heart failure dogs.
- Physiological and cellular responses, including cardiac function, β-adrenergic responsiveness, and myocyte structure, were assessed.
Main Results:
- PITA suppressed progressive cardiac dilation and improved chamber and myocyte dysfunction in heart failure dogs.
- PITA enhanced in vivo β-adrenergic responsiveness and normalized myocyte function.
- Beneficial effects were dependent on the continuity of dyssynchrony exposure, not random pacing.
Conclusions:
- PITA demonstrates potential as a novel treatment for heart failure patients with synchronous contractions who are not candidates for CRT.
- The findings suggest that transiently induced dyssynchrony can trigger beneficial biological responses leading to improved cardiac function.
- PITA offers a promising new avenue for managing heart failure by leveraging controlled asynchrony.
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.
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