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Outcome of super-responders to cardiac resynchronization therapy defined by endpoint-derived parameters of left ventricular remodeling: a two-center retrospective study

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Abstract

Aims

Various studies have attempted to identify super-responders to cardiac resynchronization therapy (CRT) by echocardiographic parameters of reverse remodeling. However, scientific evidence regarding those parameters is scarce. This study aimed at validating the definition of super-response to CRT based on the following frequently employed echocardiographic parameters: left ventricular ejection fraction (LVEF), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI).

Methods and results

We retrospectively investigated echocardiographic data and outcomes of 542 patients after CRT implantation. The primary endpoint comprised all-cause mortality, heart transplantation, ventricular assist device implantation (VAD), and hospitalization for heart failure. Secondary endpoints were hospitalization for heart failure, and the combination of all-cause mortality, heart transplantation and VAD. Two approaches were employed defining super-response based on improvement of echocardiographic parameters: one derived from the negative predictive value (NPV) for clinical endpoints, and second from best quartiles of improvement. Using the NPV method, an absolute 25 % increase in LVEF, a relative 38 % reduction in EDVI, and 46 % in ESVI were calculated as optimal cut-offs identifying 4.9, 18.5, and 21.3 % as super-responders. The best quartiles method resulted in lower cut-off values, i.e. 14 % increase in LVEF, 26 % reduction in EDVI, and 36 % in ESVI. All cut-offs except LVEF ≥25% were significantly associated with improved outcomes after 5 years (median follow-up 35.7 months).

Conclusions

NPV- and best quartile-based cut-offs validate previously applied empirical echocardiographic cut-offs to define super-response to CRT. These data provide evidence for using these empirical cut-offs in daily practice and facilitate inter-study comparability.

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References

  1. Strickberger SA, Conti J, Daoud EG, Havranek E, Mehra MR, Pina IL, Young J (2005) Patient selection for cardiac resynchronization therapy: from the Council on Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in collaboration with the Heart Rhythm Society. Circulation 111(16):2146–2150. doi:10.1161/01.cir.0000161276.09685.4a

    Article  PubMed  Google Scholar 

  2. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 14(8):803–869. doi:10.1093/eurjhf/hfs105

    Article  CAS  PubMed  Google Scholar 

  3. Steffel J, Milosevic G, Hurlimann A, Krasniqi N, Namdar M, Ruschitzka F, Luscher TF, Duru F, Holzmeister J, Hurlimann D (2011) Characteristics and long-term outcome of echocardiographic super-responders to cardiac resynchronisation therapy: ‘real world’ experience from a single tertiary care centre. Heart (Br Card Soc) 97(20):1668–1674. doi:10.1136/heartjnl-2011-300222

    Google Scholar 

  4. Antonio N, Teixeira R, Coelho L, Lourenco C, Monteiro P, Ventura M, Cristovao J, Elvas L, Goncalves L, Providencia LA (2009) Identification of ‘super-responders’ to cardiac resynchronization therapy: the importance of symptom duration and left ventricular geometry. Europace 11(3):343–349

    Article  PubMed  Google Scholar 

  5. Castellant P, Fatemi M, Bertault-Valls V, Etienne Y, Blanc JJ (2008) Cardiac resynchronization therapy: “nonresponders” and “hyperresponders”. Heart Rhythm Off J Heart Rhythm Soc 5(2):193–197. doi:10.1016/j.hrthm.2007.09.023

    Article  Google Scholar 

  6. Ypenburg C, van Bommel RJ, Borleffs CJ, Bleeker GB, Boersma E, Schalij MJ, Bax JJ (2009) Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol 53(6):483–490. doi:10.1016/j.jacc.2008.10.032

    Article  PubMed  Google Scholar 

  7. Hsu JC, Solomon SD, Bourgoun M, McNitt S, Goldenberg I, Klein H, Moss AJ, Foster E (2012) Predictors of super-response to cardiac resynchronization therapy and associated improvement in clinical outcome: the MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy) study. J Am Coll Cardiol 59(25):2366–2373. doi:10.1016/j.jacc.2012.01.065

    Article  PubMed  Google Scholar 

  8. Celebi O, Knaus T, Blaschke F, Habedank D, Dohner W, Nitardy A, Stockburger M (2012) Extraordinarily favorable left ventricular reverse remodeling through long-term cardiac resynchronization: super-response to cardiac resynchronization. Pacing Clin Electrophysiol PACE 35(7):870–876. doi:10.1111/j.1540-8159.2012.03417.x

    Article  Google Scholar 

  9. Rickard J, Kumbhani DJ, Popovic Z, Verhaert D, Manne M, Sraow D, Baranowski B, Martin DO, Lindsay BD, Grimm RA, Wilkoff BL, Tchou P (2010) Characterization of super-response to cardiac resynchronization therapy. Heart Rhythm Off J Heart Rhythm Soc 7(7):885–889. doi:10.1016/j.hrthm.2010.04.005

    Article  Google Scholar 

  10. Wasmer K, Kobe J, Andresen D, Zahn R, Spitzer SG, Jehle J, Brachmann J, Stellbrink C, Martens E, Hochadel M, Senges J, Klein H, Eckardt L (2013) Comparing outcome of patients with coronary artery disease and dilated cardiomyopathy in ICD and CRT recipients: data from the German DEVICE-registry. Clin Res Cardiol Off J Ger Card Soc 102(7):513–521. doi:10.1007/s00392-013-0559-0

    Article  Google Scholar 

  11. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, Chan YS, Kong SL, Bax JJ (2005) Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 112(11):1580–1586. doi:10.1161/circulationaha.105.538272

    Article  PubMed  Google Scholar 

  12. Poller WC, Dreger H, Schwerg M, Bondke H, Melzer C (2014) Not left ventricular lead position, but the extent of immediate asynchrony reduction predicts long-term response to cardiac resynchronization therapy. Clin Res Cardiol Off J Ger Card Soc 103(6):457–466. doi:10.1007/s00392-014-0672-8

    Article  Google Scholar 

  13. Schau T, Koglek W, Brandl J, Seifert M, Meyhofer J, Neuss M, Grimm G, Bitschnau R, Butter C (2013) Baseline vectorcardiography as a predictor of invasively determined acute hemodynamic response to cardiac resynchronization therapy. Clin Res Cardiol Off J Ger Card Soc 102(2):129–138. doi:10.1007/s00392-012-0506-5

    Article  Google Scholar 

  14. Heagerty PJ, Lumley T, Pepe MS (2000) Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56(2):337–344

    Article  CAS  PubMed  Google Scholar 

  15. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ (1987) Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76(1):44–51

    Article  CAS  PubMed  Google Scholar 

  16. Bax JJ, Schinkel AF, Boersma E, Elhendy A, Rizzello V, Maat A, Roelandt JR, van der Wall EE, Poldermans D (2004) Extensive left ventricular remodeling does not allow viable myocardium to improve in left ventricular ejection fraction after revascularization and is associated with worse long-term prognosis. Circulation 110((11 Suppl 1)):II18–II22. doi:10.1161/01.CIR.0000138195.33452.b0

    PubMed  Google Scholar 

  17. Gold MR, Linde C, Abraham WT, Gardiwal A, Daubert JC (2011) The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure. Heart Rhythm 8(5):679–684. doi:10.1016/j.hrthm.2010.12.031

    Article  PubMed  Google Scholar 

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Conflict of interest

David Hürlimann: Educational grants from Boston Scientific and Medtronic, Research grants from Biotronik, Medtronic and St. Jude Medical; Speaker honoraria and consulting fees from Biotronik, Medtronic, Sorin, St. Jude Medical.

Susann Schmidt: None.

Burkhardt Seifert: None.

Ardan M. Saguner: Educational and travel grants from Biotronik, Boston Scientific, St. Jude Medical and Sorin.

Gerhard Hindricks: Research support and speakers’ honoraria from Biotronik and St. Jude Medical.

Thomas F. Lüscher: Research grants from Biotronik, Medtronic and St. Jude Medical.

Frank Ruschitzka: Research grants and consulting fees from Biotronik, speaker honoraria from Biotronik and Boston Scientific.

Jan Steffel: Research Grants from Biotronik, Medtronic and St. Jude Medical. Consulting fees from Biotronik, Boston Scientific, Medtronic, Sorin and St. Jude Medical.

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Authors and Affiliations

  1. Department of Cardiology, Invasive Electrophysiology and Devices, University Heart Center Zurich, Zurich, Switzerland

    David Hürlimann, Susann Schmidt, Ardan M. Saguner, Thomas F. Lüscher, Frank Ruschitzka & Jan Steffel

  2. Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland

    Burkhardt Seifert

  3. Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany

    Gerhard Hindricks

  4. Division of Electrophysiology and Pacing, Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland

    Jan Steffel

Authors
  1. David Hürlimann
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  2. Susann Schmidt
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  3. Burkhardt Seifert
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  4. Ardan M. Saguner
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  5. Gerhard Hindricks
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  6. Thomas F. Lüscher
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  7. Frank Ruschitzka
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  8. Jan Steffel
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Corresponding author

Correspondence to Jan Steffel.

Additional information

D. Hürlimann and S. Schmidt contributed equally to the study.

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Hürlimann, D., Schmidt, S., Seifert, B. et al. 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, 136–144 (2015). https://doi.org/10.1007/s00392-014-0763-6

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  • DOI: https://doi.org/10.1007/s00392-014-0763-6

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