Skip to main content
Erschienen in: Clinical Research in Cardiology 11/2016

18.06.2016 | Original Paper

Sustained clinical benefit of cardiac resynchronization therapy in non-LBBB patients with prolonged PR-interval: MADIT-CRT long-term follow-up

verfasst von: Martin Stockburger, Arthur J. Moss, Helmut U. Klein, Wojciech Zareba, Ilan Goldenberg, Yitschak Biton, Scott McNitt, Valentina Kutyifa

Erschienen in: Clinical Research in Cardiology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Objective

In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only.

Methods

Non-LBBB patients (n = 534) were dichotomized based on baseline PR-interval: normal PR (PR < 230 ms), and markedly prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death.

Results

In patients with a prolonged PR-interval, CRT-D treatment related to a 67 % significant reduction in the risk of HF/death (HR = 0.33, 95 % CI 0.16–0.69, p = 0.003), 69 % decrease in HF (HR = 0.31, 95 % CI 0.14–0.68, p = 0.003), and 76 % reduction in the risk of death (HR = 0.24, 95 % CI 0.07–0.80, p = 0.020) compared to ICD-only (median follow-up 5.8 years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR = 1.49, 95 % CI 0.98–2.25, p = 0.061), and significantly increased mortality (HR = 2.27, 95 % CI 1.16–4.44, p = 0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130–150 ms and QRS > 150 ms.

Conclusion

In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration.
Literatur
1.
Zurück zum Zitat 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, Trial Investigators MADIT-CRT (2009) Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361(14):1329–1338CrossRefPubMed 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, Trial Investigators MADIT-CRT (2009) Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361(14):1329–1338CrossRefPubMed
2.
Zurück zum Zitat Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M, Cannom D, Daubert JP, Eldar M, Gold MR, Goldberger JJ, Goldenberg I, Lichstein E, Pitschner H, Rashtian M, Solomon S, Viskin S, Wang P, Moss AJ, Investigators MADIT-CRT (2011) Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation 123(10):1061–1072CrossRefPubMed Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M, Cannom D, Daubert JP, Eldar M, Gold MR, Goldberger JJ, Goldenberg I, Lichstein E, Pitschner H, Rashtian M, Solomon S, Viskin S, Wang P, Moss AJ, Investigators MADIT-CRT (2011) Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation 123(10):1061–1072CrossRefPubMed
3.
Zurück zum Zitat Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Kautzner J, Klempfner R, Kuniss M, Merkely B, Pfeffer MA, Quesada A, Viskin S, McNitt S, Polonsky B, Ghanem A, Solomon SD, Wilber D, Zareba W, Moss AJ (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370(18):1694–1701CrossRefPubMed Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW, Dan A, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Kautzner J, Klempfner R, Kuniss M, Merkely B, Pfeffer MA, Quesada A, Viskin S, McNitt S, Polonsky B, Ghanem A, Solomon SD, Wilber D, Zareba W, Moss AJ (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370(18):1694–1701CrossRefPubMed
4.
Zurück zum Zitat Kutyifa V, Stockburger M, Daubert JP, Holmqvist F, Olshansky B, Schuger C, Klein H, Goldenberg I, Brenyo A, McNitt S, Merkely B, Zareba W, Moss AJ (2014) PR-interval identifies clinical response in patients with non-left bundle branch block: a multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy substudy. Circ Arrhythm Electrophysiol 7(4):645–651CrossRefPubMed Kutyifa V, Stockburger M, Daubert JP, Holmqvist F, Olshansky B, Schuger C, Klein H, Goldenberg I, Brenyo A, McNitt S, Merkely B, Zareba W, Moss AJ (2014) PR-interval identifies clinical response in patients with non-left bundle branch block: a multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy substudy. Circ Arrhythm Electrophysiol 7(4):645–651CrossRefPubMed
5.
Zurück zum Zitat Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE, ESC Committee for Practice Guidelines (CPG), Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document Reviewers, Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bänsch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM (2013) 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 34:2281–2329CrossRefPubMed Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE, ESC Committee for Practice Guidelines (CPG), Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document Reviewers, Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bänsch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM (2013) 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 34:2281–2329CrossRefPubMed
6.
Zurück zum Zitat 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 (2010) Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363(25):2385–2395CrossRefPubMed 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 (2010) Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363(25):2385–2395CrossRefPubMed
7.
Zurück zum Zitat Gold MR, Thébault C, Linde C, Abraham WT, Gerritse B, Ghio S, St John Sutton M, Daubert JC (2012) Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study. Circulation 126(7):822–829CrossRefPubMed Gold MR, Thébault C, Linde C, Abraham WT, Gerritse B, Ghio S, St John Sutton M, Daubert JC (2012) Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study. Circulation 126(7):822–829CrossRefPubMed
8.
Zurück zum Zitat Birnie DH, Ha A, Higginson L, Sidhu K, Green M, Philippon F, Thibault B, Wells G, Tang A (2013) Impact of QRS morphology and duration on outcomes after cardiac resynchronization therapy: results from the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail 6(6):1190–1198CrossRefPubMed Birnie DH, Ha A, Higginson L, Sidhu K, Green M, Philippon F, Thibault B, Wells G, Tang A (2013) Impact of QRS morphology and duration on outcomes after cardiac resynchronization therapy: results from the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail 6(6):1190–1198CrossRefPubMed
9.
Zurück zum Zitat Moss AJ, Brown MW, Cannom DS, Daubert JP, Estes M, Foster E, Greenberg HM, Hall WJ, Higgins SL, Klein H, Pfeffer M, Wilber D, Zareba W (2005) Multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol. Ann Noninvasive Electrocardiol 10(4 Suppl):34–43CrossRefPubMed Moss AJ, Brown MW, Cannom DS, Daubert JP, Estes M, Foster E, Greenberg HM, Hall WJ, Higgins SL, Klein H, Pfeffer M, Wilber D, Zareba W (2005) Multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol. Ann Noninvasive Electrocardiol 10(4 Suppl):34–43CrossRefPubMed
10.
Zurück zum Zitat Willems JL, Robles de Medina EO, Bernard R, Coumel P, Fisch C, Krikler D, Mazur NA, Meijler FL, Mogensen L, Moret P, Pisa Z, Rautaharju PM, Surawicz B, Watanabe Y, Wellens HJJ (1985) Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 5(6):1261–1275CrossRefPubMed Willems JL, Robles de Medina EO, Bernard R, Coumel P, Fisch C, Krikler D, Mazur NA, Meijler FL, Mogensen L, Moret P, Pisa Z, Rautaharju PM, Surawicz B, Watanabe Y, Wellens HJJ (1985) Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 5(6):1261–1275CrossRefPubMed
11.
Zurück zum Zitat Schoeller R, Andresen D, Buttner P, Oezcelik K, Vey G, Schroder R (1993) First- or second-degree atrioventricular block as a risk factor in idiopathic dilated cardiomyopathy. Am J Cardiol 71(8):720–726CrossRefPubMed Schoeller R, Andresen D, Buttner P, Oezcelik K, Vey G, Schroder R (1993) First- or second-degree atrioventricular block as a risk factor in idiopathic dilated cardiomyopathy. Am J Cardiol 71(8):720–726CrossRefPubMed
12.
Zurück zum Zitat Olshansky B, Day JD, Sullivan RM, Yong P, Galle E, Steinberg JS (2012) Does cardiac resynchronization therapy provide unrecognized benefit in patients with prolonged PR-intervals? The impact of restoring atrioventricular synchrony: an analysis from the COMPANION Trial. Heart Rhythm 9(1):34–39CrossRefPubMed Olshansky B, Day JD, Sullivan RM, Yong P, Galle E, Steinberg JS (2012) Does cardiac resynchronization therapy provide unrecognized benefit in patients with prolonged PR-intervals? The impact of restoring atrioventricular synchrony: an analysis from the COMPANION Trial. Heart Rhythm 9(1):34–39CrossRefPubMed
13.
Zurück zum Zitat Cheng S, Keyes MJ, Larson MG, McCabe EL, Newton-Cheh C, Levy D, Benjamin EJ, Vasan RS, Wang TJ (2009) Long-term outcomes in individuals with prolonged PR-interval or first-degree atrioventricular block. JAMA 301(24):2571–2577CrossRefPubMedPubMedCentral Cheng S, Keyes MJ, Larson MG, McCabe EL, Newton-Cheh C, Levy D, Benjamin EJ, Vasan RS, Wang TJ (2009) Long-term outcomes in individuals with prolonged PR-interval or first-degree atrioventricular block. JAMA 301(24):2571–2577CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Hochleitner M, Hörtnagl H, Ng CK, Hörtnagl H, Gschnitzer F, Zechmann W (1990) Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. Am J Cardiol 66:198–202CrossRefPubMed Hochleitner M, Hörtnagl H, Ng CK, Hörtnagl H, Gschnitzer F, Zechmann W (1990) Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. Am J Cardiol 66:198–202CrossRefPubMed
15.
Zurück zum Zitat Hochleitner M, Hörtnagl H, Hörtnagl H, Fridrich L, Gschnitzer F (1992) Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol 70(15):1320–1325CrossRefPubMed Hochleitner M, Hörtnagl H, Hörtnagl H, Fridrich L, Gschnitzer F (1992) Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol 70(15):1320–1325CrossRefPubMed
16.
Zurück zum Zitat Kloosterman M, Rienstra M, Mulder BA, Van Gelder IC, Maass AH (2015) Atrial reverse remodelling is associated with outcome of cardiac resynchronization therapy. Europace (Epub ahead of print) Kloosterman M, Rienstra M, Mulder BA, Van Gelder IC, Maass AH (2015) Atrial reverse remodelling is associated with outcome of cardiac resynchronization therapy. Europace (Epub ahead of print)
17.
Zurück zum Zitat Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, Dickstein K, Ford I, Gorcsan J 3rd, Gras D, Krum H, Sogaard P, Holzmeister J, EchoCRT Study Group (2013) Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 369(15):1395–1405CrossRefPubMed Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, Dickstein K, Ford I, Gorcsan J 3rd, Gras D, Krum H, Sogaard P, Holzmeister J, EchoCRT Study Group (2013) Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 369(15):1395–1405CrossRefPubMed
18.
Zurück zum Zitat Hürlimann D, Schmidt S, Seifert B, Saguner AM, Hindricks G, Lüscher TF, Ruschitzka F, Steffel J (2015) Outcome of super-responders to cardiac resynchronization therapy defined by endpoint-derived parameters of left ventricular remodeling: a two-center retrospective study. Clin Res Cardiol. 104(2):136–144CrossRefPubMed Hürlimann D, Schmidt S, Seifert B, Saguner AM, Hindricks G, Lüscher TF, Ruschitzka F, Steffel J (2015) Outcome of super-responders to cardiac resynchronization therapy defined by endpoint-derived parameters of left ventricular remodeling: a two-center retrospective study. Clin Res Cardiol. 104(2):136–144CrossRefPubMed
19.
Zurück zum Zitat Franke J, Keppler J, Abadei AK, Bajrovic A, Meme L, Zugck C, Raake PW, Zitron E, Katus HA, Frankenstein L (2016) Long-term outcome of patients with and without super-response to CRT-D. Clin Res Cardiol 105(4):341–348CrossRefPubMed Franke J, Keppler J, Abadei AK, Bajrovic A, Meme L, Zugck C, Raake PW, Zitron E, Katus HA, Frankenstein L (2016) Long-term outcome of patients with and without super-response to CRT-D. Clin Res Cardiol 105(4):341–348CrossRefPubMed
Metadaten
Titel
Sustained clinical benefit of cardiac resynchronization therapy in non-LBBB patients with prolonged PR-interval: MADIT-CRT long-term follow-up
verfasst von
Martin Stockburger
Arthur J. Moss
Helmut U. Klein
Wojciech Zareba
Ilan Goldenberg
Yitschak Biton
Scott McNitt
Valentina Kutyifa
Publikationsdatum
18.06.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 11/2016
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-016-1003-z

Weitere Artikel der Ausgabe 11/2016

Clinical Research in Cardiology 11/2016 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.