This Article Figures Only Full Text Full Text (PDF) Online Appendix View Related Genuine Article on CVN View Cardiosource Journal Scan All Versions of this Article: j.jacc.2008.08.027v1 j.jacc.2008.08.027v2 52/23/1834    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Linde, C. Search for Related Content PubMed PubMed Citation Articles by Linde, C. Related Collections Related Articles

EXPEDITED PUBLICATION: CARDIAC RESYNCHRONIZATION

Randomized Trial of Cardiac Resynchronization in Mildly Symptomatic Heart Failure Patients and in Asymptomatic Patients With Left Ventricular Dysfunction and Previous Heart Failure Symptoms

Cecilia Linde, MD, PhD^_*,_*, William T. Abraham, MD, FACC, Michael R. Gold, MD, PhD, Martin St. John Sutton, MD, Stefano Ghio, MD^¶, Claude Daubert, MD^|| REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group

^_* Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
Division of Cardiovascular Medicine and the Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio
Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
^¶ Policlinico San Matteo, Pavia, Italy
^|| Département de Cardiologie, CHU, Rennes, France

Manuscript received June 13, 2008; revised manuscript received July 31, 2008, accepted August 14, 2008.

^_* Reprint requests and correspondence: Dr. Cecilia Linde, Department of Cardiology, Karolinska University Hospital, S-17176 Stockholm, Sweden (Email: cecilia.linde{at}ki.se).

Objectives: We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms.

Background: Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS.

Methods: Six hundred ten patients with NYHA functional class I or II heart failure with a QRS 120 ms and a LV ejection fraction 40% received a CRT device (±defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use.

Results: The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (–18.4 ± 29.5 ml/m² vs. –1.3 ± 23.4 ml/m², p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03).

Conclusions: The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (±defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154 [ClinicalTrials.gov] ).

Key Words: cardiac resynchronization therapy • heart failure • randomized controlled trial • biventricular pacing • reverse remodeling

Abbreviations and Acronyms   AEAC = Adverse Event Advisory/Endpoint Committee   CRT = cardiac resynchronization therapy   HF = heart failure   ICD = implantable cardioverter-defibrillator   LV = left ventricular   LVESVI = left ventricular end-systolic volume index   NYHA = New York Heart Association

Related Articles

Cardiac Resynchronization for Asymptomatic or Mildly Symptomatic Heart Failure: A Bridge Too Far?

Christophe Leclercq, Philippe Mabo, and Jean Noel Trochu
J. Am. Coll. Cardiol. 2008 52: 1844-1846. [Full Text] [PDF]

This article has been cited by other articles:

				D. J. van Veldhuisen, A. H. Maass, S. G. Priori, P. Stolt, I. C. van Gelder, K. Dickstein, and K. Swedberg Implementation of device therapy (cardiac resynchronization therapy and implantable cardioverter defibrillator) for patients with heart failure in Europe: changes from 2004 to 2008 Eur J Heart Fail, December 1, 2009; 11(12): 1143 - 1151. [Abstract] [Full Text] [PDF]

				J. G.F. Cleland, A. P. Coletta, A. Yassin, L. Buga, A. Torabi, and A. L. Clark Clinical trials update from the European Society of Cardiology Meeting 2009: AAA, RELY, PROTECT, ACTIVE-I, European CRT survey, German pre-SCD II registry, and MADIT-CRT Eur J Heart Fail, December 1, 2009; 11(12): 1214 - 1219. [Abstract] [Full Text] [PDF]

				C. Daubert, M. R. Gold, W. T. Abraham, S. Ghio, C. Hassager, G. Goode, T. Szili-Torok, C. Linde, and on behalf of the REVERSE Study Group Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction: Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial J. Am. Coll. Cardiol., November 10, 2009; 54(20): 1837 - 1846. [Abstract] [Full Text] [PDF]

				D. V. Exner Is it Time to Expand the Use of Cardiac Resynchronization Therapy to Patients With Mildly Symptomatic Heart Failure? J. Am. Coll. Cardiol., November 10, 2009; 54(20): 1847 - 1849. [Full Text] [PDF]

				M. St. John Sutton, S. Ghio, T. Plappert, L. Tavazzi, L. Scelsi, C. Daubert, W. T. Abraham, M. R. Gold, C. Hassager, J. M. Herre, et al. Cardiac Resynchronization Induces Major Structural and Functional Reverse Remodeling in Patients With New York Heart Association Class I/II Heart Failure Circulation, November 10, 2009; 120(19): 1858 - 1865. [Abstract] [Full Text] [PDF]

				G. S. Francis and W.H. Wilson Tang Early Cardiac Resynchronization Therapy and Reverse Remodeling in Patients With Mild Heart Failure: Is It Time? Circulation, November 10, 2009; 120(19): 1845 - 1846. [Full Text] [PDF]

				G. Breithardt MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy): cardiac resynchronization therapy towards early management of heart failure Eur. Heart J., November 1, 2009; 30(21): 2551 - 2553. [Full Text] [PDF]

				J. C. Daubert, C. Leclercq, and P. Mabo Cardiac resynchronization therapy in combination with implantable cardioverter-defibrillator Europace, November 1, 2009; 11(suppl_5): v87 - v92. [Abstract] [Full Text] [PDF]

				C. Linde Cardiac resynchronization therapy in mild heart failure Europace, November 1, 2009; 11(suppl_5): v72 - v76. [Abstract] [Full Text] [PDF]

				K. Dickstein, N. Bogale, S. Priori, A. Auricchio, J. G. Cleland, A. Gitt, T. Limbourg, C. Linde, D. J. van Veldhuisen, J. Brugada, et al. The European cardiac resynchronization therapy survey Eur. Heart J., October 2, 2009; 30(20): 2450 - 2460. [Abstract] [Full Text] [PDF]

				J. Steffel and D. Hurlimann Current practice of cardiac resynchronization therapy (CRT) in the real world: insights from the European CRT survey Eur. Heart J., October 2, 2009; 30(20): 2433 - 2435. [Full Text] [PDF]

				M. Jessup MADIT-CRT -- Breathtaking or Time to Catch Our Breath? N. Engl. J. Med., October 1, 2009; 361(14): 1394 - 1396. [Full Text] [PDF]

				A. J. Moss, W. J. Hall, D. S. Cannom, H. Klein, M. W. Brown, J. P. Daubert, N.A. M. Estes III, E. Foster, H. Greenberg, S. L. Higgins, et al. Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events N. Engl. J. Med., October 1, 2009; 361(14): 1329 - 1338. [Abstract] [Full Text] [PDF]

				G. M. Marcus, E. Keung, and M. M. Scheinman The year in review of clinical cardiac electrophysiology. J. Am. Coll. Cardiol., August 25, 2009; 54(9): 777 - 787. [Full Text] [PDF]

				L. Mont, E. Guasch, and A. Berruezo An implantable defibrillator and what else? Eur. Heart J., July 1, 2009; 30(13): 1551 - 1553. [Full Text] [PDF]

				S. Osswald, B. Schaer, M. Kuhne, and C. Sticherling No benefit from cardiac resynchronization therapy in asymptomatic patients. J. Am. Coll. Cardiol., June 9, 2009; 53(23): 2198 - 2198. [Full Text] [PDF]

				C. Linde, W. T. Abraham, M. R. Gold, M. S. J. Sutton, S. Ghio, C. Daubert, and REVERSE Study Group Reply. J. Am. Coll. Cardiol., June 9, 2009; 53(23): 2198 - 2199. [Full Text] [PDF]

				J. G.F. Cleland, A. P. Coletta, A. L. Clark, and D. Cullington Clinical trials update from the American College of Cardiology 2009: ADMIRE-HF, PRIMA, STICH, REVERSE, IRIS, partial ventricular support, FIX-HF-5, vagal stimulation, REVIVAL-3, pre-RELAX-AHF, ACTIVE-A, HF-ACTION, JUPITER, AURORA, and OMEGA Eur J Heart Fail, June 1, 2009; 11(6): 622 - 630. [Abstract] [Full Text] [PDF]

				M. Malik Precise electrocardiographic measurements and clinical sense Europace, May 1, 2009; 11(5): 550 - 553. [Full Text] [PDF]

				R. M Cubbon and K. K A Witte Cardiac resynchronisation therapy for chronic heart failure and conduction delay BMJ, April 28, 2009; 338(apr28_2): b1265 - b1265. [Full Text]

				J. G.F. Cleland and D. Cullington Digoxin: Quo Vadis? Circ Heart Fail, March 1, 2009; 2(2): 81 - 85. [Full Text] [PDF]

				The CRT Survey Scientific Committee European cardiac resynchronization therapy survey: rationale and design Eur J Heart Fail, March 1, 2009; 11(3): 326 - 330. [Abstract] [Full Text] [PDF]

				Is Cardiac Resynchronization Therapy Beneficial in Milder Heart Failure? Journal Watch (General), January 13, 2009; 2009(113): 4 - 4. [Full Text]

				J. McMurray, M. Petrie, K. Swedberg, M. Komajda, S. Anker, and R. Gardner CHAPTER 23 Heart Failure ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				C. Leclercq, P. Mabo, and J. N. Trochu Cardiac Resynchronization for Asymptomatic or Mildly Symptomatic Heart Failure: A Bridge Too Far? J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1844 - 1846. [Full Text] [PDF]