Impact of physiologic pacing versus right ventricular pacing among patients with left ventricular ejection fraction greater than 35%: A systematic review for the 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay

A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
Published:November 06, 2018DOI:


      It is unclear whether physiologic pacing by either cardiac biventricular pacing (BiVP) or His bundle pacing (HisBP) may prevent adverse structural and functional consequences known to occur among some patients who receive right ventricular pacing (RVP).


      Our analysis sought to review existing literature to determine if BiVP and/or HisBP might prevent adverse remodeling and be associated with structural, functional, and clinical advantages compared with RVP among patients without severe left ventricular dysfunction (>35%) who required permanent pacing because of heart block.


      A literature search was conducted using MEDLINE (through PubMed) and Embase to identify randomized trials and observational studies comparing the effects of BiVP or HisBP versus RVP on measurements of left ventricular dimensions, left ventricular ejection fraction (LVEF), heart failure functional classification, quality of life, 6-minute walk, hospitalizations, and mortality. Data from studies that met the appropriate population, intervention, comparator, and outcomes of interest were abstracted for meta-analysis. Studies that reported pooled outcomes among patients with LVEF both above and below 35% could not be included in the meta-analysis because of strict relationships with industry procedures that preclude retrieval of industry-retained unpublished data on the subset of patients with preserved left ventricular function.


      Evidence from 8 studies, including a total of 679 patients meeting the prespecified criteria for inclusion, was identified. Results were compared for BiVP versus RVP, HisBP versus RVP, and BiVP+HisBP versus RVP. Among patients who received physiologic pacing with either BiVP or HisBP, the LV end-diastolic and end-systolic volumes were significantly lower (mean duration of follow-up: 1.64 years; –2.77 mL [95% CI –4.37 to –1.1 mL]; p=0.001; and –7.09 mL [95% CI –11.27 to –2.91; p=0.0009) and LVEF remained preserved or increased (mean duration of follow-up: 1.57 years; 5.328% [95% CI: 2.86%–7.8%; p<0.0001). Data on clinical impact such as functional status and quality of life were not definitive. Data on hospitalizations were unavailable. There was no effect on mortality. Several studies stratified results by LVEF and found that patients with LVEF >35% but ≤52% were more likely to receive benefit from physiologic pacing. Patients with chronic atrial fibrillation who underwent atrioventricular node ablation and pacemaker implant demonstrated clear improvement in LVEF with BiVP or HisBP versus RVP.


      Among patients with LVEF >35%, the LVEF remained preserved or increased with either BiVP or HisBP compared with RVP. However, patient-centered clinical outcome improvement appears to be limited primarily to patients who have chronic atrial fibrillation with rapid ventricular response rates and have undergone atrioventricular node ablation.


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        • Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine (U.S.)
        Clinical Practice Guidelines We Can Trust.
        National Academies Press, Washington, DC2011
        • Committee on Standards for Systematic Reviews of Comparative Effectiveness Research, Institute of Medicine (U.S.)
        Finding What Works in Health Care: Standards for Systematic Reviews.
        National Academies Press, Washington, DC2011
      1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Available at: and Accessed: September 23, 2018.

        • Jacobs A.K.
        • Kushner F.G.
        • Ettinger S.M.
        • et al.
        ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2013; 61: 213-265
        • Halperin J.L.
        • Levine G.N.
        • Al-Khatib S.M.
        • et al.
        Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2016; 67: 1572-1574
        • Jacobs A.K.
        • Anderson J.L.
        • Halperin J.L.
        The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 64: 1373-1384
        • Uslan D.Z.
        • Tleyjeh I.M.
        • Baddour L.M.
        • et al.
        Temporal trends in permanent pacemaker implantation: a population-based study.
        Am Heart J. 2008; 155: 896-903
        • Karpawich P.P.
        • Rabah R.
        • Haas J.E.
        Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block.
        Pacing Clin Electrophysiol. 1999; 22: 1372-1377
        • van Oosterhout M.F.
        • Prinzen F.W.
        • Arts T.
        • et al.
        Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall.
        Circulation. 1998; 98: 588-595
        • Thambo J.B.
        • Bordachar P.
        • Garrigue S.
        • et al.
        Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing.
        Circulation. 2004; 110: 3766-3772
        • O’Keefe Jr., J.H.
        • Abuissa H.
        • Jones P.G.
        • et al.
        Effect of chronic right ventricular apical pacing on left ventricular function.
        Am J Cardiol. 2005; 95: 771-773
        • Lee M.A.
        • Dae M.W.
        • Langberg J.J.
        • et al.
        Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology.
        J Am Coll Cardiol. 1994; 24: 225-232
        • Tse H.F.
        • Yu C.
        • Wong K.K.
        • et al.
        Functional abnormalities in patients with permanent right ventricular pacing: the effect of sites of electrical stimulation.
        J Am Coll Cardiol. 2002; 40: 1451-1458
        • Nielsen J.C.
        • Andersen H.R.
        • Thomsen P.E.
        • et al.
        Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single-chamber atrial or ventricular pacing.
        Circulation. 1998; 97: 987-995
        • Sweeney M.O.
        • Hellkamp A.S.
        • Ellenbogen K.A.
        • et al.
        Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction.
        Circulation. 2003; 107: 2932-2937
        • 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
        • Abraham W.T.
        • Fisher W.G.
        • Smith A.L.
        • et al.
        Cardiac resynchronization in chronic heart failure.
        N Engl J Med. 2002; 346: 1845-1853
        • Bristow M.R.
        • Saxon L.A.
        • Boehmer J.
        • et al.
        Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.
        N Engl J Med. 2004; 350: 2140-2150
        • Cleland J.G.
        • Daubert J.C.
        • Erdmann E.
        • et al.
        The effect of cardiac resynchronization on morbidity and mortality in heart failure.
        N Engl J Med. 2005; 352: 1539-1549
        • Kindermann M.
        • Hennen B.
        • Jung J.
        • et al.
        Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE).
        J Am Coll Cardiol. 2006; 47: 1927-1937
        • Young J.B.
        • Abraham W.T.
        • Smith A.L.
        • et al.
        Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial.
        JAMA. 2003; 289: 2685-2694
        • Catanzariti D.
        • Maines M.
        • Cemin C.
        • et al.
        Permanent direct His bundle pacing does not induce ventricular dyssynchrony unlike conventional right ventricular apical pacing. An intrapatient acute comparison study.
        J Interv Card Electrophysiol. 2006; 16: 81-92
        • Deshmukh P.
        • Casavant D.A.
        • Romanyshyn M.
        • et al.
        Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation.
        Circulation. 2000; 101: 869-877
        • Fang F.
        • Zhang Q.
        • Chan J.Y.
        • et al.
        Early pacing-induced systolic dyssynchrony is a strong predictor of left ventricular adverse remodeling: analysis from the Pacing to Avoid Cardiac Enlargement (PACE) trial.
        Int J Cardiol. 2013; 168: 723-728
        • Zanon F.
        • Bacchiega E.
        • Rampin L.
        • et al.
        Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study.
        Europace. 2008; 10: 580-587
        • Curtis A.B.
        • Worley S.J.
        • Chung E.S.
        • et al.
        Improvement in clinical outcomes with biventricular versus right ventricular pacing: The BLOCK HF Study.
        J Am Coll Cardiol. 2016; 67: 2148-2157
        • Borenstein M.
        • Hedges L.V.
        • Higgins J.P.T.
        • Rothstein H.R.
        Introduction to Meta-Analysis.
        John Wiley & Sons, West Sussex, UK2009
        • Albertsen A.E.
        • Mortensen P.T.
        • Jensen H.K.
        • et al.
        Adverse effect of right ventricular pacing prevented by biventricular pacing during long-term follow-up: a randomized comparison.
        Eur J Echocardiogr. 2011; 12: 767-772
        • 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
        • Yu C.M.
        • Fang F.
        • Luo X.X.
        • et al.
        Long-term follow-up results of the pacing to avoid cardiac enlargement (PACE) trial.
        Eur J Heart Fail. 2014; 16: 1016-1025
        • Stockburger M.
        • Gomez-Doblas J.J.
        • Lamas G.
        • et al.
        Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: results from a multicentre international randomized trial (PREVENT-HF).
        Eur J Heart Fail. 2011; 13: 633-641
        • Kronborg M.B.
        • Mortensen P.T.
        • Poulsen S.H.
        • et al.
        His or para-His pacing preserves left ventricular function in atrioventricular block: a double-blind, randomized, crossover study.
        Europace. 2014; 16: 1189-1196
        • Sharma P.S.
        • Dandamudi G.
        • Naperkowski A.
        • et al.
        Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice.
        Heart Rhythm. 2015; 12: 305-312
        • Occhetta E.
        • Bortnik M.
        • Magnani A.
        • et al.
        Prevention of ventricular desynchronization by permanent para-Hisian pacing after atrioventricular node ablation in chronic atrial fibrillation: a crossover, blinded, randomized study versus apical right ventricular pacing.
        J Am Coll Cardiol. 2006; 47: 1938-1945
        • Brignole M.
        • Botto G.
        • Mont L.
        • et al.
        Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial.
        Eur Heart J. 2011; 32: 2420-2429
        • Funck R.C.
        • Blanc J.J.
        • Mueller H.H.
        • et al.
        Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the ‘Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)’ study.
        Europace. 2006; 8: 629-635
        • Funck R.C.
        • Mueller H.H.
        • Lunati M.
        • et al.
        Characteristics of a large sample of candidates for permanent ventricular pacing included in the Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization Study (BioPace).
        Europace. 2014; 16: 354-362