His-bundle pacing vs biventricular pacing following atrioventricular nodal ablation in patients with atrial fibrillation and reduced ejection fraction: A multicenter, randomized, crossover study—The ALTERNATIVE-AF trial


      Atrioventricular nodal ablation (AVNA) combined with biventricular pacing (BVP) improves outcomes in patients with persistent atrial fibrillation (AF), adequate rate control, and reduced left ventricular ejection fraction (LVEF). His-bundle pacing (HBP) delivers physiological ventricular activation and is a promising alternative to BVP.


      The purpose of this trial was to compare HBP with BVP following AVNA.


      In this multicenter, prospective, randomized crossover trial, we recruited patients with persistent AF and reduced LVEF (≤40%). All patients underwent AVNA and received both HBP and BVP. Patients were randomized to either HBP or BVP for 9 months (phase 1), then were switched to the alternative pacing modality for the next 9 months (phase 2). The primary endpoint was change in LVEF.


      Fifty patients (age 64.3 ± 10.3 years; ventricular rate 93.1 ± 19.9 bpm; 72% male) were enrolled. Thirty-eight patients completed the 2 phases and were included in the crossover analysis. A significant improvement in LVEF was observed with HBP compared to BVP (phase 1: ΔLVEFHBP 21.3% and ΔLVEFBVP 16.7%; phase 2: ΔLVEFHBP 3.5% and ΔLVEFBVP –2.4%; Pgeneralized additive model = 0.015). Significant improvements in left ventricular end-diastolic diameter, New York Heart Association functional class, and B-type natriuretic peptide level were observed with both pacing modalities compared with baseline, whereas no significant differences were observed between HBP and BVP.


      HBP delivers a modest but significant improvement in LVEF in patients with persistent AF, impaired ventricular function, and narrow QRS duration post-AVNA compared with BVP. Larger long-term trials are required to confirm the additional improvements in function with HBP.

      Graphical abstract


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        • Wang T.J.
        • Larson M.G.
        • Levy D.
        • et al.
        Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study.
        Circulation. 2003; 107: 2920-2925
        • Al-Khatib S.M.
        • Benjamin E.J.
        • Albert C.M.
        • et al.
        Advancing research on the complex interrelations between atrial fibrillation and heart failure: a report from a US National Heart, Lung, and Blood Institute Virtual Workshop.
        Circulation. 2020; 141: 1915-1926
        • Maisel W.H.
        • Stevenson L.W.
        Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy.
        Am J Cardiol. 2003; 91 (2D–8D)
        • Huang W.
        • Su L.
        • Wu S.
        Pacing treatment of atrial fibrillation patients with heart failure: His bundle pacing combined with atrioventricular node ablation.
        Card Electrophysiol Clin. 2018; 10: 519-535
        • Wood M.A.
        • Brown-Mahoney C.
        • Kay G.N.
        • Ellenbogen K.A.
        Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis.
        Circulation. 2000; 101: 1138-1144
        • Glikson M.
        • Nielsen J.C.
        • Kronborg M.B.
        • et al.
        2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy.
        Eur Heart J. 2021; 42: 3427-3520
        • Wilkoff B.L.
        • Cook J.R.
        • Epstein A.E.
        • et al.
        Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial.
        JAMA. 2002; 288: 3115-3123
        • Tops L.F.
        • Schalij M.J.
        • Holman E.R.
        • van Erven L.
        • van der Wall E.E.
        • Bax J.J.
        Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrioventricular node ablation.
        J Am Coll Cardiol. 2006; 48: 1642-1648
        • Doshi R.N.
        • Daoud E.G.
        • Fellows C.
        • et al.
        Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study).
        J Cardiovasc Electrophysiol. 2005; 16: 1160-1165
        • Orlov M.V.
        • Gardin J.M.
        • Slawsky M.
        • et al.
        Biventricular pacing improves cardiac function and prevents further left atrial remodeling in patients with symptomatic atrial fibrillation after atrioventricular node ablation.
        Am Heart J. 2010; 159: 264-270
        • Leclercq C.
        • Walker S.
        • Linde C.
        • et al.
        Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation.
        Eur Heart J. 2002; 23: 1780-1787
        • Brignole M.
        • Pokushalov E.
        • Pentimalli F.
        • et al.
        A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS.
        Eur Heart J. 2018; 39: 3999-4008
        • Brignole M.
        • Pentimalli F.
        • Palmisano P.
        • et al.
        AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial.
        Eur Heart J. 2021; 42: 4731-4739
        • Ploux S.
        • Eschalier R.
        • Whinnett Z.I.
        • et al.
        Electrical dyssynchrony induced by biventricular pacing: Implications for patient selection and therapy improvement.
        Heart Rhythm. 2015; 12: 782-791
        • Huang W.
        • Su L.
        • Wu S.
        • et al.
        Benefits of permanent His bundle pacing combined with atrioventricular node ablation in atrial fibrillation patients with heart failure with both preserved and reduced left ventricular ejection fraction.
        J Am Heart Assoc. 2017; 6e005309
        • Vijayaraman P.
        • Subzposh F.A.
        • Naperkowski A.
        Atrioventricular node ablation and His bundle pacing.
        Europace. 2017; 19 (:iv10–iv16)
        • Su L.
        • Cai M.
        • Wu S.
        • Wang S.
        • et al.
        Long-term performance and risk factors analysis after permanent His-bundle pacing and atrioventricular node ablation in patients with atrial fibrillation and heart failure.
        Europace. 2020; 22 (:ii19–ii26)
        • Wang S.
        • Wu S.
        • Xu L.
        • et al.
        Feasibility and efficacy of His bundle pacing or left bundle pacing combined with atrioventricular node ablation in patients with persistent atrial fibrillation and implantable cardioverter-defibrillator therapy.
        J Am Heart Assoc. 2019; 8e014253
        • Keene D.
        • Arnold A.D.
        • Jastrzebski M.
        • et al.
        His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: insights from a large international observational study.
        J Cardiovasc Electrophysiol. 2019; 30: 1984-1993
        • Su L.
        • Wu S.
        • Wang S.
        • et al.
        Pacing parameters and success rates of permanent His-bundle pacing in patients with narrow QRS: a single-centre experience.
        Europace. 2019; 21: 763-770
        • Sato T.
        • Soejima K.
        • Maeda A.
        • et al.
        Safety of distal His bundle pacing via the right ventricle backed up by adjacent ventricular capture.
        JACC Clin Electrophysiol. 2021; 7: 513-521
        • Huang W.
        • Su L.
        • Wu S.
        • et al.
        Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block.
        Heart. 2019; 105: 137-143
        • Vinther M.
        • Risum N.
        • Svendsen J.H.
        • Møgelvang R.
        • Philbert B.T.
        A randomized trial of His pacing versus biventricular pacing in symptomatic HF patients with left bundle branch block (His-alternative).
        JACC Clin Electrophysiol. 2021; 7: 1422-1432
        • Žižek D.
        • Antolič B.
        • Mežnar A.Z.
        • et al.
        Biventricular versus His bundle pacing after atrioventricular node ablation in heart failure patients with narrow QRS.
        Acta Cardiol. 2022; 77: 222-230
        • Ruschitzka F.
        • Abraham W.T.
        • Singh J.P.
        • et al.
        Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.
        N Engl J Med. 2013; 369: 1395-1405
        • Su L.
        • Wang S.
        • Wu S.
        • et al.
        Long-term safety and feasibility of left bundle branch pacing in a large single-center study.
        Circ Arrhythm Electrophysiol. 2021; 14: e009261
        • Wu S.
        • Cai M.
        • Zheng R.
        • et al.
        Impact of QRS morphology on response to conduction system pacing after atrioventricular junction ablation.
        ESC Heart Fail. 2021; 8: 1195-1203

      Linked Article

      • Advancing alternatives for atrial fibrillation in heart failure: Ablate and pace is back
        Heart RhythmVol. 19Issue 12
        • Preview
          The physiological pacing movement continues its rapid evolution, perhaps faster than any other advances in the field of electrophysiology over the past 5 years. While stimulation and recruitment of the intrinsic conduction system is intuitive, teleological, and physiologically compelling, the mounting evidence still lags behind the enthusiasm that is driving widespread clinical adoption. Single-arm feasibility registries populate the literature, and comparative studies between His bundle pacing (HBP) and conventional biventricular pacing (BiV) are few to date.
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