INTRODUCTION: The aim of this study was to investigate the predictors of long-term clinical outcome of heart failure (HF) patients who survived first year after initiation of cardiac resynchronization therapy (CRT). METHODS: This was a single-center observational cohort study of CRT patients implanted because of symptomatic HF with reduced ejection fraction between 2005 and 2013. Left ventricle (LV) diameters and ejection fraction, New York Heart Association (NYHA) class, and level of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) were assessed at baseline and 12 months after CRT implantation. Their predictive power for long-term HF hospitalization and mortality, and cardiac and all-cause mortality was investigated. RESULTS: A total of 315 patients with left bundle branch block or intraventricular conduction delay who survived >1 year after CRT implantation were analyzed in the current study. During a follow-up period of 4.8±2.1 years from CRT implantation, 35.2% patients died from cardiac (19.3%) or non-cardiac (15.9%) causes. Post-CRT LV ejection fraction and LV end-systolic diameter (either 12-month value or the change from baseline) were equally predictive for clinical events. For NT-proBNP, however, the 12-month level was a stronger predictor than the change from baseline. Both reverse LV remodeling and 12-month level of NT-proBNP were independent and comparable predictors of CRT-related clinical outcome, while NT-proBNP response had the strongest association with all-cause mortality. When post-CRT relative change of LV end-systolic diameter and 12-month level of NT-proBNP (dichotomized at -12.3% and 1230 ng/L, respectively) were combined, subgroups of very-high and very-low risk patients were identified. CONCLUSION: The level of NT-proBNP and reverse LV remodeling at one year after CRT are independent and complementary predictors of future clinical events. Their combination may help to improve the risk stratification of CRT patients.

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiology Regional Hospital Liberec Liberec Czech Republic

Faculty of Health Studies Technical University of Liberec Liberec Czech Republic

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Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346: 1845–1853. 10.1056/NEJMoa013168 PubMed DOI

Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350: 2140–50. 10.1056/NEJMoa032423 PubMed DOI

Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events. N Engl J Med. 2009;361: 1329–1338. 10.1056/NEJMoa0906431 PubMed DOI

Birnie DH, Tang AS. The problem of non-response to cardiac resynchronization therapy. Curr Opin Cardiol. 2006;21: 20–26. 10.1097/01.hco.0000198983.93755.99 PubMed DOI

Roubicek T, Wichterle D, Kucera P, Nedbal P, Kupec J, Sedlakova J, et al. Left Ventricular Lead Electrical Delay Is a Predictor of Mortality in Patients with Cardiac Resynchronization Therapy. Circ Arrhythmia Electrophysiol. 2015; 8: 1113–21. 10.1161/CIRCEP.115.003004 PubMed DOI

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37: 2129–2200. 10.1093/eurheartj/ehw128 PubMed DOI

Strauss DG, Selvester RH, Wagner GS. Defining Left Bundle Branch Block in the Era of Cardiac Resynchronization Therapy. Am J Cardiol. 2011;107: 927–934. 10.1016/j.amjcard.2010.11.010 PubMed DOI

Wang TJ. Assessing the Role of Circulating, Genetic, and Imaging Biomarkers in Cardiovascular Risk Prediction. Circulation. 2011;123: 551–565. 10.1161/CIRCULATIONAHA.109.912568 PubMed DOI PMC

Goksuluk D, Korkmaz S, Zararsiz GKA. EasyROC: An interactive web-tool for ROC curve analysis using R language environment. R J. 2016;8: 213–230.

Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, et al. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005;112: 1580–1586. 10.1161/CIRCULATIONAHA.105.538272 PubMed DOI

Solomon SD, Foster E, Bourgoun M, Shah A, Viloria E, Brown MW, et al. Effect of Cardiac Resynchronization Therapy on Reverse Remodeling and Relation to Outcome: Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy. Circulation. 2010;122: 985–992. 10.1161/CIRCULATIONAHA.110.955039 PubMed DOI

Foley PW, Chalil S, Khadjooi K, Irwin N, Smith RE, Leyva F. Left ventricular reverse remodelling, long-term clinical outcome, and mode of death after cardiac resynchronization therapy. Eur J Hear Fail. 2011;13: 43–51. 10.1093/eurjhf/hfq182 PubMed DOI

Park JH, Negishi K, Grimm RA, Popovic Z, Stanton T, Wilkoff BL, et al. Echocardiographic predictors of reverse remodeling after cardiac resynchronization therapy and subsequent events. Circ Cardiovasc Imaging. 2013;6: 864–72. 10.1161/CIRCIMAGING.112.000026 PubMed DOI

Bertini M, Höke U, van Bommel RJ, Ng ACT, Shanks M, Nucifora G, et al. Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival. Eur Heart J Cardiovasc Imaging. 2013;14: 774–81. 10.1093/ehjci/jes290 PubMed DOI

Boidol J, Średniawa B, Kowalski O, Szulik M, Mazurek M, Sokal A, et al. Many response criteria are poor predictors of outcomes after cardiac resynchronization therapy: validation using data from the randomized trial. Europace. 2013;15: 835–44. 10.1093/europace/eus390 PubMed DOI

Gold MR, Daubert C, Abraham WT, Ghio S, St. John Sutton M, Hudnall JH, et al. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: Results of the REVERSE study. Heart Rhythm. 2015;12: 524–530. 10.1016/j.hrthm.2014.11.014 PubMed DOI PMC

Menet A, Guyomar Y, Ennezat P-V, Graux P, Castel AL, Delelis F, et al. Prognostic value of left ventricular reverse remodeling and performance improvement after cardiac resynchronization therapy: A prospective study. Int J Cardiol. 2016;204: 6–11. 10.1016/j.ijcard.2015.11.091 PubMed DOI

Fornwalt BK, Sprague WW, Bedell P, Suever JD, Gerritse B, Merlino JD, et al. Agreement is poor among current criteria used to define response to cardiac resynchronization therapy. Circulation. 2010;121: 1985–91. 10.1161/CIRCULATIONAHA.109.910778 PubMed DOI PMC

Auger D, Van Bommel RJ, Bertini M, Delgado V, Ng ACT, Ewe SH, et al. Prevalence and characteristics of patients with clinical improvement but not significant left ventricular reverse remodeling after cardiac resynchronization therapy. Am Heart J. 2010;160: 737–743. 10.1016/j.ahj.2010.07.016 PubMed DOI

Sinha AM, Filzmaier K, Breithardt OA, Kunz D, Graf J, Markus KU, et al. Usefulness of brain natriuretic peptide release as a surrogate marker of the efficacy of long-term cardiac resynchronization therapy in patients with heart failure. Am J Cardiol. 2003;91: 755–758. 10.1016/s0002-9149(02)03425-2 PubMed DOI

Molhoek SG, Bax JJ, vanErven L, Bootsma M, Steendijk P, Lentjes E, et al. Atrial and brain natriuretic peptides as markers of response to resynchronisation therapy. Heart. 2004;90: 97–98. 10.1136/heart.90.1.97 PubMed DOI PMC

Erol-Yilmaz A, Verberne HJ, Schrama TA, Hrudova J, De Winter RJ, Van Eck-Smit BLF, et al. Cardiac resynchronization induces favorable neurohumoral changes. PACE—Pacing Clin Electrophysiol. 2005;28: 304–310. 10.1111/j.1540-8159.2005.09508.x PubMed DOI

Yu C-M, Fung JW-H, Zhang Q, Chan C-K, Chan I, Chan Y-S, et al. Improvement of Serum NT-ProBNP Predicts Improvement in Cardiac Function and Favorable Prognosis After Cardiac Resynchronization Therapy for Heart Failure. J Card Fail. 2005;11(5 Suppl): S42–46. 10.1016/j.cardfail.2005.04.007 PubMed DOI

Kubanek M, Malek I, Bytesnik J, Fridl P, Riedlbauchova L, Karasova L, et al. Decrease in plasma B-type natriuretic peptide early after initiation of cardiac resynchronization therapy predicts clinical improvement at 12 months. Eur J Hear Fail. 2006;8: 832–840. 10.1016/j.ejheart.2006.02.006 PubMed DOI

Pitzalis MV, Iacoviello M, Di Serio F, Romito R, Guida P, De Tommasi E, et al. Prognostic value of brain natriuretic peptide in the management of patients receiving cardiac resynchronization therapy. Eur J Heart Fail. 2006;8: 509–514. 10.1016/j.ejheart.2005.10.013 PubMed DOI

Delgado RM, Palanichamy N, Radovancevic R, Vrtovec B, Radovancevic B. Brain natriuretic peptide levels and response to cardiac resynchronization therapy in heart failure patients. Congest Hear Fail. 2006;12: 250–253. 10.1111/j.1527-5299.2006.05469.x PubMed DOI

Magne J, Dubois M, Champagne J, Dumesnil JG, Pibarot P, Philippon F, et al. Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy. Cardiovasc Ultrasound. 2009;7: 39 10.1186/1476-7120-7-39 PubMed DOI PMC

Arrigo M, Truong QA, Szymonifka J, Rivas-Lasarte M, Tolppanen H, Sadoune M, et al. Mid-regional pro-atrial natriuretic peptide to predict clinical course in heart failure patients undergoing cardiac resynchronization therapy. EP Eur. 2017;19: 1848–1854. 10.1093/europace/euw305 PubMed DOI PMC

Cleland JGF, Daubert J-C, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005; 352:1539–1549. 10.1056/NEJMoa050496 PubMed DOI

Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J. 2007;28: 1592–1597. 10.1093/eurheartj/ehl505 PubMed DOI

Cleland J, Freemantle N, Ghio S, Fruhwald F, Shankar A, Marijanowski M, et al. Predicting the long-term effects of cardiac resynchronization therapy on mortality from baseline variables and the early response a report from the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial. J Am Coll Cardiol. 2008;52: 438–45. 10.1016/j.jacc.2008.04.036 PubMed DOI

Brenyo A, Barsheshet A, Rao M, Huang DT, Zareba W, McNitt S, et al. Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure. Circ Hear Fail. 2013;6: 998–1004. 10.1161/CIRCHEARTFAILURE.112.000174 PubMed DOI

Hoogslag GE, Höke U, Thijssen J, Auger D, Marsan NA, Wolterbeek R, et al. Clinical, echocardiographic, and neurohormonal response to cardiac resynchronization therapy: are they interchangeable? Pacing Clin Electrophysiol. 2013:11: 1391–401. 10.1111/pace.12214 PubMed DOI

Bakos Z, Chatterjee NC, Reitan C, Singh JP, Borgquist R. Prediction of clinical outcome in patients treated with cardiac resynchronization therapy—the role of NT-ProBNP and a combined response score. BMC Cardiovasc Disord. 2018;18:70 10.1186/s12872-018-0802-8 PubMed DOI PMC