Prevalence and incidence of intra-ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from PARADIGM-HF and ATMOSPHERE

Søren Lund Kristensen, Davide Castagno, Li Shen, Pardeep S Jhund, Kieran F Docherty, Rasmus Rørth, William T Abraham, Akshay S Desai, Kenneth Dickstein, Jean L Rouleau, Michael R Zile, Karl Swedberg, Milton Packer, Scott D Solomon, Lars Køber, John J V McMurray, PARADIGM-HF and ATMOSPHERE Committees and Investigators., Søren Lund Kristensen, Davide Castagno, Li Shen, Pardeep S Jhund, Kieran F Docherty, Rasmus Rørth, William T Abraham, Akshay S Desai, Kenneth Dickstein, Jean L Rouleau, Michael R Zile, Karl Swedberg, Milton Packer, Scott D Solomon, Lars Køber, John J V McMurray, PARADIGM-HF and ATMOSPHERE Committees and Investigators.

Abstract

Aims: The importance of intra-ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials.

Methods and results: The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device. At baseline, 1789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) right bundle branch block (RBBB), 454 (3.8%) non-specific IVCD, 2588 (21.8%) 'mildly abnormal' QRS (110-129 ms) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% confidence interval) LBBB 1.36 (1.23-1.50), RBBB 1.54 (1.31-1.79), non-specific IVCD 1.65 (1.40-1.94) and QRS 110-129 ms 1.35 (1.23-1.47), compared with QRS duration <110 ms. A total of 1234 (15.6%) patients developed new-onset QRS widening ≥130 ms (6.1 per 100 patient-years). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 patient-years) and was associated with a higher risk of the primary composite outcome [hazard ratio 1.42 (1.12-1.82)].

Conclusion: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat electrocardiogram review.

Trial registration: ClinicalTrials.gov Identifier NCT0083658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).

Trial registration: ClinicalTrials.gov NCT01035255 NCT00853658.

Keywords: Cardiac resynchronization therapy; Electrocardiography; Heart failure; Left bundle branch block; Prognosis.

© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

References

    1. Grines CL, Marsalese DL, Brodie B, Griffin J, Donohue B, Costantini CR, Balestrini C, Stone G, Wharton T, Esente P, Spain M, Moses J, Nobuyoshi M, Ayres M, Jones D, Mason D, Sachs D, Grines LL, O'Neill W. Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocardial Infarction. J Am Coll Cardiol 1998;31:967-972.
    1. Lund LH, Jurga J, Edner M, Benson L, Dahlstrom U, Linde C, Alehagen U. Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction. Eur Heart J 2013;34:529-539.
    1. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
    1. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549.
    1. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W; MADIT-CRT Trial Investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:1329-1338.
    1. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS, Rouleau JL; 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.
    1. Hawkins NM, Wang D, McMurray JJ, Pfeffer MA, Swedberg K, Granger CB, Yusuf S, Pocock SJ, Ostergren J, Michelson EL, Dunn FG; CHARM Investigators and Committees. Prevalence and prognostic impact of bundle branch block in patients with heart failure: evidence from the CHARM programme. Eur J Heart Fail 2007;9:510-517.
    1. Zannad F, Huvelle E, Dickstein K, van Veldhuisen DJ, Stellbrink C, Kober L, Cazeau S, Ritter P, Maggioni AP, Ferrari R, Lechat P. Left bundle branch block as a risk factor for progression to heart failure. Eur J Heart Fail 2007;9:7-14.
    1. Lee SJ, McCulloch C, Mangat I, Foster E, De Marco T, Saxon LA. Isolated bundle branch block and left ventricular dysfunction. J Card Fail 2003;9:87-92.
    1. McMurray JJ, Krum H, Abraham WT, Dickstein K, Kober LV, Desai AS, Solomon SD, Greenlaw N, Ali MA, Chiang Y, Shao Q, Tarnesby G, Massie BM; ATMOSPHERE Committees Investigators. Aliskiren, enalapril, or aliskiren and enalapril in heart failure. N Engl J Med 2016;374:1521-1532.
    1. Krum H, Massie B, Abraham WT, Dickstein K, Kober L, McMurray JJ, Desai A, Gimpelewicz C, Kandra A, Reimund B, Rattunde H, Armbrecht J; ATMOSPHERE Investigators. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study. Eur J Heart Fail 2011;13:107-114.
    1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail 2013;15:1062-1073.
    1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz M, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Committees Investigators. Baseline characteristics and treatment of patients in Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail 2014;16:817-825.
    1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
    1. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.
    1. Sohaib SM, Finegold JA, Nijjer SS, Hossain R, Linde C, Levy WC, Sutton R, Kanagaratnam P, Francis DP, Whinnett ZI. Opportunity to increase life span in narrow QRS cardiac resynchronization therapy recipients by deactivating ventricular pacing: evidence from randomized controlled trials. JACC Heart Fail 2015;3:327-336.
    1. Cannon JA, Collier TJ, Shen L, Swedberg K, Krum H, Van Veldhuisen DJ, Vincent J, Pocock SJ, Pitt B, Zannad F, McMurray JJ. Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail 2015;17:707-716.
    1. Abdel-Qadir HM, Tu JV, Austin PC, Wang JT, Lee DS. Bundle branch block patterns and long-term outcomes in heart failure. Int J Cardiol 2011;146:213-218.
    1. Baldasseroni S, Gentile A, Gorini M, Marchionni N, Marini M, Masotti G, Porcu M, Maggioni AP; Italian Network on Congestive Heart Failure Investigators. Intraventricular conduction defects in patients with congestive heart failure: left but not right bundle branch block is an independent predictor of prognosis. A report from the Italian Network on Congestive Heart Failure (IN-CHF database). Ital Heart J 2003;4:607-613.
    1. Braunschweig F, Linde C, Benson L, Stahlberg M, Dahlstrom U, Lund LH. New York Heart Association functional class, QRS duration, and survival in heart failure with reduced ejection fraction: implications for cardiac resychronization therapy. Eur J Heart Fail 2017;19:366-376.
    1. Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN; Department of Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. QRS duration and mortality in patients with congestive heart failure. Am Heart J 2002;143:1085-1091.
    1. Shenkman HJ, Pampati V, Khandelwal AK, McKinnon J, Nori D, Kaatz S, Sandberg KR, McCullough PA. Congestive heart failure and QRS duration: establishing prognosis study. Chest 2002;122:528-534.
    1. Kalra PR, Sharma R, Shamim W, Doehner W, Wensel R, Bolger AP, Genth-Zotz S, Cicoira M, Coats AJ, Anker SD. Clinical characteristics and survival of patients with chronic heart failure and prolonged QRS duration. Int J Cardiol 2002;86:225-231.
    1. Hofmann M, Bauer R, Handrock R, Weidinger G, Goedel-Meinen L. Prognostic value of the QRS duration in patients with heart failure: a subgroup analysis from 24 centers of Val-HeFT. J Card Fail 2005;11:523-528.
    1. Wang NC, Maggioni AP, Konstam MA, Zannad F, Krasa HB, Burnett JC Jr, Grinfeld L, Swedberg K, Udelson JE, Cook T, Traver B, Zimmer C, Orlandi C, Gheorghiade M; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Clinical implications of QRS duration in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction. JAMA 2008;299:2656-2666.
    1. Fosbol EL, Seibaek M, Brendorp B, Moller DV, Ersboll M, Torp-Pedersen C, Kober L; Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) Study Group. Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction. Eur J Heart Fail 2007;9:814-819.
    1. Leyva F, Foley PW, Chalil S, Ratib K, Smith RE, Prinzen F, Auricchio A. Cardiac resynchronization therapy guided by late gadolinium-enhancement cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2011;13:29.
    1. Giudici MC, Abu-El-Haija B, Schrumpf PE, Bhave PD, Al Khiami B, Barold SS. Right ventricular septal pacing in patients with right bundle branch block. J Electrocardiol 2015;48:626-629.
    1. Sharma PS, Naperkowski A, Bauch TD, Chan JYS, Arnold AD, Whinnett ZI, Ellenbogen KA, Vijayaraman P. Permanent his bundle pacing for cardiac resynchronization therapy in patients with heart failure and right bundle branch block. Circ Arrhythm Electrophysiol 2018;11:e006613.
    1. Clark AL, Goode K, Cleland JG. The prevalence and incidence of left bundle branch block in ambulant patients with chronic heart failure. Eur J Heart Fail 2008;10:696-702.
    1. Rav-Acha M, Nujidat A, Farkash R, Medina A, Ilan M, Klutstein M, Butnaru A, Weitsman T, Glikson M, Hasin T. Delayed prolongation of the QRS interval in patients with left ventricular dysfunction. Int J Cardiol 2019;296:71-75.

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