Long-term outcomes in nonprogressors to cardiac resynchronization therapy

Published:November 07, 2022DOI:


      Among patients with heart failure undergoing cardiac resynchronization therapy (CRT), patients with a minimal change in left ventricular ejection fraction (LVEF) have recently been defined as “nonprogressors” rather than as “nonresponders.” Little is known regarding long-term outcomes of nonprogressors.


      We sought to evaluate outcomes in patients undergoing CRT on the basis of echocardiographically determined response status.


      We reviewed the medical charts of patients with an LVEF of ≤35% and a QRS duration of ≥120 ms undergoing CRT at the Cleveland Clinic, Johns Hopkins Hospital, and Johns Hopkins Bayview Medical Center between 2003 and 2014. Response to CRT was defined on the basis of LVEF change as follows: super-responders ≥20%, responders 6%–19%, nonprogressors 0%–5%, and progressors <0%. Survival free of left ventricular assist device (LVAD) and heart transplant was compared on the basis of response classification.


      A total of 1058 patients were included and had a mean follow-up 8.7 ± 5.4 years, over which time there were 606 end points (37 LVAD implants, 32 heart transplants, and 537 deaths). Survival free of LVAD and heart transplant differed significantly between response groups after CRT both in the mid-term (4 years) and in the long-term (8.7 ± 5.4 years), with super-responders achieving the best outcomes and progressors the worst (P < .001). In multivariate analysis, nonprogressors had superior outcomes to progressors (P = .02) at 4 years of follow-up. Over the duration of follow-up (8.7 ± 5.4 years), there was no significant difference in survival between those 2 groups (P = .18).


      Nonprogressors to CRT have superior medium-term outcomes but similar long-term outcomes to progressors and inferior outcomes to responders and super-responders.


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        • Moss A.J.
        • Hall W.J.
        • Cannom D.S.
        • et al.
        • MADIT-CRT Trial Investigators
        Cardiac- resynchronization therapy for the prevention of heart-failure events.
        N Engl J Med. 2009; 361: 1329-1338
        • Tang A.S.
        • Wells G.A.
        • Talajic M.
        • et al.
        Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure.
        N Engl J Med. 2010; 363: 2385-2395
        • Cleland J.G.
        • Daubert J.C.
        • Dermann E.
        • et al.
        The effect of cardiac resynchronization on morbidity and mortality in heart failure.
        N Engl J Med. 2005; 352: 1539-1549
        • Birne D.H.
        • Tang A.S.
        The problem of non-response to cardiac resynchronization therapy.
        Curr Opin Cardiol. 2006; 219: 20-26
        • Rickard J.
        • Kumbhani D.J.
        • Popovic Z.
        • et al.
        Characterization of super-response to cardiac resynchronization therapy.
        Heart Rhythm. 2010; 7: 885-889
        • Antonio N.
        • Teixeira R.
        • Coelho L.
        • et al.
        Identification of ‘super-responders’ to cardiac resynchronization therapy: the importance of symptom duration and left ventricular geometry.
        Europace. 2009; 11: 343-349
        • Steffel J.
        • Ruschtizka F.
        Superreponse to cardiac resynchronization therapy.
        Circulation. 2014; 130: 87-90
        • Mullens W.
        • Aurrichio A.
        • Martens P.
        • et al.
        Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care. A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.
        Eur J Heart Fail. 2020; 12: 2349-2369
        • 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 form 5 prospective studies.
        Heart Rhythm. 2022; 19: 595-603
        • 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
        • Rickard J.
        • Michtalik H.
        • Sharma R.
        • et al.
        Predictors of response to cardiac resynchronization therapy: a systematic review.
        Int J Cardiol. 2016; 225: 345-352
        • Manne M.
        • Rickard J.
        • Varma N.
        • Chung M.K.
        • Tchou P.
        Normalization of left ventricular ejection fraction after cardiac resynchronization therapy normalizes survival.
        Pacing Clin Electrophysiol. 2013; 36: 970-977
        • Nijst P.
        • Martens P.
        • Dauw J.
        • et al.
        Withdrawal of neurohumoral blockade after cardiac resynchronization therapy.
        J Am Coll Cardiol. 2020; 12: 1426-1438
        • Varma N.
        • Boehmer J.
        • Bharghava K.
        • et al.
        Evaluation, management, and outcomes of patients poorly responsive to cardiac resynchronization device therapy.
        J Am Coll Cardiol. 2019; 74: 2588-2603
        • Altman R.K.
        • Parks K.A.
        • Schlett C.L.
        • et al.
        Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes.
        Eur Heart J. 2012; 33: 2181-2188
        • Gorodeski E.Z.
        • Magnelli-Reyes C.
        • Moennich L.A.
        • Grimaldi A.
        • Rickard J.
        Cardiac resynchronization therapy-heart failure (CRT-HF) clinic: a novel model of care.
        PLoS One. 2019; 14e0222610
        • Mullens W.
        • Grimm R.A.
        • Verga T.
        • et al.
        Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program.
        J Am Coll Cardiol. 2009; 53: 765-773
        • Jastrzebski M.
        • Kielbasa G.
        • Cano O.
        • et al.
        Left bundle area pacing outcomes: the multicenter European MELOS study.
        Eur Heart J. 2022; 43: 4161-4173
        • Vijayaraman P.
        • Herweg B.
        • Verma A.
        • et al.
        Rescue left bundle branch area pacing in coronary venous lead failure or nonresponse to biventricular pacing: results from International LBBAP Collaborative Study Group.
        Heart Rhythm. 2022; 8: 1272-1280

      Linked Article

      • Redefining the Response to CRT – Mission Possible?
        Heart Rhythm
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          Cardiac resynchronization therapy (CRT) is one of the most effective treatment modalities for patients with systolic heart failure and a wide QRS complex as it can improve survival, reduce hospitalization, and provide symptomatic relief (1). However, not all patients respond even when the therapy is indicated. Alternatively, a super response has been seen in select patients who have normalization or near normalization of the systolic function and elimination of symptoms. Definitions of CRT response vary widely and depend upon endpoints used.
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