Randomized controlled trial comparing simultaneous versus optimized sequential interventricular stimulation during cardiac resynchronization therapy

William T. Abraham, Angel R. León, Martin G. St. John Sutton, Steven J. Keteyian, Ann M. Fieberg, Ed Chinchoy, Garrie Haas

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality and improves symptoms in patients with systolic heart failure (HF) and ventricular dyssynchrony. This randomized, double-blind, controlled study evaluated whether optimizing the interventricular stimulating interval (V-V) to sequentially activate the ventricles is clinically better than simultaneous V-V stimulation during CRT. Methods: Patients with New York Heart Association (NYHA) III or IV HF, meeting both CRT and implantable cardioverter-defibrillator indications, randomly received either simultaneous CRT or CRT with optimized V-V settings for 6 months. Patients also underwent echocardiography-guided atrioventricular delay optimization to maximize left ventricular filling. The V-V optimization involved minimizing the left ventricular septal to posterior wall motion delay during CRT. The primary objective was to demonstrate noninferiority using a clinical composite end point that included mortality, HF hospitalization, NYHA functional class, and patient global assessment. Secondary end points included changes in NYHA classification, 6-minute hall walk distance, quality of life, peak VO2, and event-free survival. Results: The composite score improved in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized patients (P <.001, for noninferiority). A prespecified test of superiority showed that more optimized patients improved (P =.03). New York Heart Association functional class improved in 58.0% of simultaneous patients versus 75.0% of optimized patients (P =.01). No significant differences in exercise capacity, quality of life, peak VO 2, or HF-related event rate between the 2 groups were observed. Conclusions: These findings demonstrate modest clinical benefit with optimized sequential V-V stimulation during CRT in patients with NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool for increasing the proportion of patients who respond to CRT.

Original languageEnglish (US)
Pages (from-to)735-741
Number of pages7
JournalAmerican Heart Journal
Issue number5
StatePublished - Nov 2012

Bibliographical note

Funding Information:
This study was supported by Medtronic, Inc, Minneapolis, MN.


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