Association of interventricular activation delay with clinical outcomes in cardiac resynchronization therapy

Published:November 23, 2022DOI:


      Pacing at sites of longest interventricular delay has been associated with greater reverse remodeling in cardiac resynchronization therapy (CRT). However, the effects of pacing at such sites on clinical outcomes is less well studied.


      The purpose of this study was to assess the association between interventricular delay and clinical outcomes in CRT patients implanted with quadripolar left ventricular (LV) leads.


      RALLY-X4 was a registry study of the Acuity X4 quadripolar LV leads. Interventricular delay was measured during unpaced basal rhythm from the right ventricular (RV) lead to the LV lead electrode (E1 to E4) chosen for CRT pacing. Patients were stratified by median RV-LV delay (80 ms) into short and long delay groups; they also were analyzed by multivariable modeling. The primary composite outcome measure was all-cause mortality and heart failure hospitalization (HFH) at 18 months.


      A total of 581 patients had complete RV-LV delay data. Mean LV ejection fraction was 27%, and 73% had typical left bundle branch block. Predictors of long RV-LV delay included female sex, left bundle branch block, and QRS duration >150 ms. Survival free of the primary outcome at 18-month follow-up was 87% in the long activation delay group compared with 77% in the short delay group (P = .0042). Multivariate analysis showed that RV-LV delay was an independent predictor of survival free of HFH (P = .028).


      Among CRT patients with quadripolar LV pacing leads, longer baseline interventricular activation delay was significantly associated with the composite endpoint of all-cause mortality and HFH.


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        • Cleland J.G.
        • Abraham W.T.
        • Linde C.
        • et al.
        An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure.
        Eur Heart J. 2013; 34: 3547-3556
        • Moss A.J.
        • Hall W.J.
        • Cannom D.S.
        • et al.
        Cardiac-resynchronization therapy for the prevention of heart-failure events.
        N Engl J Med. 2009; 361: 1329-1338
        • Gold M.R.
        • Rickard J.
        • Daubert J.C.
        • Zimmerman P.
        • Linde C.
        Redefining the classifications of response to cardiac resynchronization therapy: results from the REVERSE study.
        JACC Clin Electrophysiol. 2021; 7: 871-880
        • Chung E.S.
        • Gold M.R.
        • Abraham W.T.
        • et al.
        The importance of early evaluation after cardiac resynchronization therapy to redefine response: pooled individual patient analysis from 5 prospective studies.
        Heart Rhythm. 2022; 19: 595-603
        • Thebault C.
        • Donal E.
        • Meunier C.
        • et al.
        • REVERSE study group
        Sites of left and right ventricular lead implantation and response to cardiac resynchronization therapy observations from the REVERSE trial.
        Eur Heart J. 2012; 33: 2662-2671
        • Singh J.P.
        • Klein H.U.
        • Huang D.T.
        • et al.
        Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial.
        Circulation. 2011; 123: 1159-1166
        • Gold M.R.
        • Birgersdotter-Green U.
        • Singh J.P.
        • et al.
        The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy.
        Eur Heart J. 2011; 32: 2516-2524
        • Gold M.R.
        • Singh J.P.
        • Ellenbogen K.A.
        • et al.
        Interventricular electrical delay is predictive of response to cardiac resynchronization therapy.
        JACC Clin Electrophysiol. 2016; 2: 438-447
        • Field M.E.
        • Yu N.
        • Wold N.
        • Gold M.R.
        Comparison of measures of ventricular delay on cardiac resynchronization therapy response.
        Heart Rhythm. 2020; 17: 615-620
        • Soejima K.
        • Kondo Y.
        • Sasaki S.
        • et al.
        Intracardiac conduction time as a predictor of cardiac resynchronization therapy response: results of the BIOSELECT pilot study.
        Heart Rhythm O2. 2021; 2: 588-596
        • Kosztin A.
        • Kutyifa V.
        • Nagy V.K.
        • et al.
        Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients.
        Europace. 2016; 18: 550-559
        • Mittal S.
        • Nair D.
        • Padanilam B.J.
        • et al.
        Performance of anatomically designed quadripolar left ventricular leads: results from the NAVIGATE X4 clinical trial.
        J Cardiovasc Electrophysiol. 2016; 27: 1199-1205
        • Turakhia M.P.
        • Cao M.
        • Fischer A.
        • et al.
        Reduced mortality associated with quadripolar compared to bipolar left ventricular leads in cardiac resynchronization therapy.
        JACC Clin Electrophysiol. 2016; 2: 426-433
        • Erath J.W.
        • Benz A.P.
        • Hohnloser S.H.
        • Vamos M.
        Clinical outcomes after implantation of quadripolar compared to bipolar left ventricular leads in patients undergoing cardiac resynchronization therapy: a systematic review and meta-analysis.
        Europace. 2019; 21: 1543-1549
        • Leyva F.
        • Zegard A.
        • Qiu T.
        • Acquaye E.
        • Ferrante G.
        • Walton J.
        • Marshall H.
        Cardiac resynchronization therapy using quadripolar versus non-quadripolar left ventricular leads programmed to biventricular pacing with single-site left ventricular pacing: impact on survival and heart failure hospitalization.
        J Am Heart Assoc. 2017; 6e007026
        • Hakemi E.U.
        • Doukky R.
        • Parzynski C.S.
        • Curtis J.P.
        • Madias C.
        Quadripolar versus bipolar leads in cardiac resynchronization therapy: an analysis of the National Cardiovascular Data Registry.
        Heart Rhythm. 2020; 17: 81-89
        • Burri H.
        • Schrage M.O.
        • Morani G.
        • et al.
        Effect of lead design and pacing vector on electrical parameters of quadripolar coronary sinus leads: the RALLY-X4 study.
        Pacing Clin Electrophysiol. 2019; 42: 1018-1025
        • Chatterjee N.A.
        • Gold M.R.
        • Waggoner A.D.
        • et al.
        Longer left ventricular electric delay reduces mitral regurgitation after cardiac resynchronization therapy: mechanistic insights from the SMART-AV study (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy).
        Circ Arrhythm Electrophysiol. 2016; 9e004346
        • Gold M.R.
        • Yu Y.
        • Wold N.
        • Day J.D.
        The role of interventricular conduction delay to predict clinical response with cardiac resynchronization therapy.
        Heart Rhythm. 2017; 14: 1748-1755
        • Kandala J.
        • Upadhyay G.A.
        • Altman R.K.
        • et al.
        Electrical delay in apically positioned left ventricular leads and clinical outcome after cardiac resynchronization therapy.
        J Cardiovasc Electrophysiol. 2013; 24: 182-187
        • Koerber S.M.
        • Field M.E.
        • Cobb D.B.
        • Gregoski M.J.
        • Sturdivant J.L.
        • Gold M.R.
        Electrical delays in quadripolar leads with cardiac resynchronization therapy.
        J Cardiovasc Electrophysiol. 2021; 32: 2498-2503

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      • In the right place at the right (conduction) time
        Heart Rhythm
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          Approximately one-third of patients with cardiac resynchronization therapy (CRT) do not experience clinical benefit despite fulfilling the criteria for guideline-recommended device implant. To reduce the non-responder rate and enhance the benefit of CRT in responders, robust research studies on CRT have concentrated on the optimal selection of CRT candidates and ideal sites of ventricular leads. Based on acute hemodynamic data from early CRT studies, the left ventricular (LV) lead position was guided by anatomical criteria with the lateral wall being the preferable location.
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