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Published in: Journal of Interventional Cardiac Electrophysiology 2/2011

01-11-2011 | Review Paper

Cardiac resynchronization therapy in patients with mild heart failure: a systematic review and meta-analysis

Authors: Pasquale Santangeli, Luigi Di Biase, Gemma Pelargonio, Antonio Dello Russo, Michela Casella, Stefano Bartoletti, J. David Burkhardt, Prasant Mohanty, Pietro Santarelli, Andrea Natale

Published in: Journal of Interventional Cardiac Electrophysiology | Issue 2/2011

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Abstract

Purpose

Cardiac resynchronization therapy (CRT) reduces symptoms and improves survival in patients with advanced heart failure (New York Heart Association (NYHA) functional class III–IV), reduced ejection fraction, and wide QRS complex. Whether CRT has the same benefit also in asymptomatic or mildly symptomatic heart failure patients is controversial. Our objective is to summarize the available evidence on the effects of CRT in asymptomatic or mildly symptomatic (NYHA I–II) heart failure patients.

Methods

We searched major web databases for randomized controlled trials of CRT in patients with mild heart failure (NYHA functional class I–II). Data regarding all-cause mortality, heart failure events, left ventricular (LV) volumes and ejection fraction, and worsening of NYHA functional class were extracted.

Results

We identified five trials (CONTAK-CD, MIRACLE ICD-II, REVERSE, MADIT-CRT, and RAFT) that enrolled 4,213 patients (91% with NYHA II functional class). Primary analysis excluded the CONTAK-CD, which was not specifically conducted on patients with mild heart failure. At pooled analysis, CRT decreased mortality (odds ratio (OR), 0.78 [95% confidence interval (CI)], 0.63 to 0.97; p = 0.024) and heart failure events (OR, 0.63 [95% CI, 0.52 to 0.76], p < 0.001), induced a significant LV reverse remodeling (weighted mean difference (WMD) of LV ejection fraction \( = + 4.8\% \left[ {95\% \,{\text{CI,}} + 0.9\,{\text{to}} + 8.7\% } \right] \), p = 0.015 and WMD of LV end-systolic volume index \( = - 19.4\,{\text{mL}}/{{\text{m}}^2}\left[ {95\% \,{\text{CI,}} - 18.2\,{\text{to}} - 20.7\,{\text{mL}}/{{\text{m}}^2}} \right] \), p < 0.001) and prevented the progression of heart failure symptoms (OR for worsening of NYHA functional class = 0.54 [95% CI, 0.31 to 0.93], p = 0.026). Inclusion of the CONTAK-CD did not change the results.

Conclusions

Among patients with mild (NYHA II) heart failure, CRT reduces mortality and the risk of heart failure events, induces a favorable LV reverse remodeling and slows the progression of heart failure symptoms.
Literature
2.
go back to reference Lloyd-Jones, D., Adams, R. J., Brown, T. M., Carnethon, M., Dai, S., De Simone, G., et al. (2010). Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation, 121, e46–e215.PubMedCrossRef Lloyd-Jones, D., Adams, R. J., Brown, T. M., Carnethon, M., Dai, S., De Simone, G., et al. (2010). Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation, 121, e46–e215.PubMedCrossRef
3.
go back to reference Ahmed, A. (2007). A propensity matched study of New York Heart Association class and natural history end points in heart failure. The American Journal of Cardiology, 99, 549–553.PubMedCrossRef Ahmed, A. (2007). A propensity matched study of New York Heart Association class and natural history end points in heart failure. The American Journal of Cardiology, 99, 549–553.PubMedCrossRef
4.
go back to reference Anonymous (1999). Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet, 353, 2001–2007. Anonymous (1999). Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet, 353, 2001–2007.
5.
go back to reference Anonymous (1997). Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet, 349, 375–380. Anonymous (1997). Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet, 349, 375–380.
6.
go back to reference Jong, P., Yusuf, S., Rousseau, M. F., Ahn, S. A., & Bangdiwala, S. I. (2003). Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet, 361, 1843–1848.PubMedCrossRef Jong, P., Yusuf, S., Rousseau, M. F., Ahn, S. A., & Bangdiwala, S. I. (2003). Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet, 361, 1843–1848.PubMedCrossRef
7.
go back to reference Cleland, J. G., Daubert, J. C., Erdmann, E., Freemantle, N., Gras, D., Kappenberger, L., et al. (2005). The effect of cardiac resynchronization on morbidity and mortality in heart failure. The New England Journal of Medicine, 352, 1539–1549.PubMedCrossRef Cleland, J. G., Daubert, J. C., Erdmann, E., Freemantle, N., Gras, D., Kappenberger, L., et al. (2005). The effect of cardiac resynchronization on morbidity and mortality in heart failure. The New England Journal of Medicine, 352, 1539–1549.PubMedCrossRef
8.
go back to reference Bristow, M. R., Saxon, L. A., Boehmer, J., Krueger, S., Kass, D. A., De Marco, T., et al. (2004). Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. The New England Journal of Medicine, 350, 2140–2150.PubMedCrossRef Bristow, M. R., Saxon, L. A., Boehmer, J., Krueger, S., Kass, D. A., De Marco, T., et al. (2004). Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. The New England Journal of Medicine, 350, 2140–2150.PubMedCrossRef
9.
go back to reference Abraham, W. T., Fisher, W. G., Smith, A. L., Delurgio, D. B., Leon, A. R., Loh, E., et al. (2002). Cardiac resynchronization in chronic heart failure. The New England Journal of Medicine, 346, 1845–1853.PubMedCrossRef Abraham, W. T., Fisher, W. G., Smith, A. L., Delurgio, D. B., Leon, A. R., Loh, E., et al. (2002). Cardiac resynchronization in chronic heart failure. The New England Journal of Medicine, 346, 1845–1853.PubMedCrossRef
10.
go back to reference Abraham, W. T., Young, J. B., Leon, A. R., Adler, S., Bank, A. J., Hall, S. A., et al. (2004). Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation, 110, 2864–2868.PubMedCrossRef Abraham, W. T., Young, J. B., Leon, A. R., Adler, S., Bank, A. J., Hall, S. A., et al. (2004). Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation, 110, 2864–2868.PubMedCrossRef
11.
go back to reference Higgins, S. L., Hummel, J. D., Niazi, I. K., Giudici, M. C., Worley, S. J., Saxon, L. A., et al. (2003). Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. Journal of the American College of Cardiology, 42, 1454–1459.PubMedCrossRef Higgins, S. L., Hummel, J. D., Niazi, I. K., Giudici, M. C., Worley, S. J., Saxon, L. A., et al. (2003). Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. Journal of the American College of Cardiology, 42, 1454–1459.PubMedCrossRef
12.
go back to reference Linde, C., Abraham, W. T., Gold, M. R., St John Sutton, M., Ghio, S., & Daubert, C. (2008). Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. Journal of the American College of Cardiology, 52, 1834–1843.PubMedCrossRef Linde, C., Abraham, W. T., Gold, M. R., St John Sutton, M., Ghio, S., & Daubert, C. (2008). Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. Journal of the American College of Cardiology, 52, 1834–1843.PubMedCrossRef
13.
go back to reference Moss, A. J., Hall, W. J., Cannom, D. S., Klein, H., Brown, M. W., Daubert, J. P., et al. (2009). Cardiac-resynchronization therapy for the prevention of heart-failure events. The New England Journal of Medicine, 361, 1329–1338.PubMedCrossRef Moss, A. J., Hall, W. J., Cannom, D. S., Klein, H., Brown, M. W., Daubert, J. P., et al. (2009). Cardiac-resynchronization therapy for the prevention of heart-failure events. The New England Journal of Medicine, 361, 1329–1338.PubMedCrossRef
15.
go back to reference Desai, A. S., Fang, J. C., Maisel, W. H., & Baughman, K. L. (2004). Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA, 292, 2874–2879.PubMedCrossRef Desai, A. S., Fang, J. C., Maisel, W. H., & Baughman, K. L. (2004). Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA, 292, 2874–2879.PubMedCrossRef
16.
go back to reference Lubitz, S. A., Leong-Sit, P., Fine, N., Kramer, D. B., Singh, J., & Ellinor, P. T. (2010). Effectiveness of cardiac resynchronization therapy in mild congestive heart failure: systematic review and meta-analysis of randomized trials. European Journal of Heart Failure, 12, 360–366.PubMedCrossRef Lubitz, S. A., Leong-Sit, P., Fine, N., Kramer, D. B., Singh, J., & Ellinor, P. T. (2010). Effectiveness of cardiac resynchronization therapy in mild congestive heart failure: systematic review and meta-analysis of randomized trials. European Journal of Heart Failure, 12, 360–366.PubMedCrossRef
17.
go back to reference Egger, M., Davey Smith, G., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629–634.PubMedCrossRef Egger, M., Davey Smith, G., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629–634.PubMedCrossRef
18.
go back to reference Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ, 339, b2535.PubMedCrossRef Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ, 339, b2535.PubMedCrossRef
19.
go back to reference Daubert, C., Gold, M. R., Abraham, W. T., Ghio, S., Hassager, C., Goode, G., et al. (2009). 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. Journal of the American College of Cardiology, 54, 1837–1846.PubMedCrossRef Daubert, C., Gold, M. R., Abraham, W. T., Ghio, S., Hassager, C., Goode, G., et al. (2009). 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. Journal of the American College of Cardiology, 54, 1837–1846.PubMedCrossRef
20.
go back to reference Hollis, S., & Campbell, F. (1999). What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ, 319, 670–674.PubMedCrossRef Hollis, S., & Campbell, F. (1999). What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ, 319, 670–674.PubMedCrossRef
21.
go back to reference Solomon, S. D., Foster, E., Bourgoun, M., Shah, A., Viloria, E., Brown, M. W., et al. (2010). Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation, 122, 985–992.PubMedCrossRef Solomon, S. D., Foster, E., Bourgoun, M., Shah, A., Viloria, E., Brown, M. W., et al. (2010). Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation, 122, 985–992.PubMedCrossRef
22.
go back to reference St John Sutton, M., Ghio, S., Plappert, T., Tavazzi, L., Scelsi, L., Daubert, C., et al. (2009). Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation, 120, 1858–1865.PubMedCrossRef St John Sutton, M., Ghio, S., Plappert, T., Tavazzi, L., Scelsi, L., Daubert, C., et al. (2009). Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation, 120, 1858–1865.PubMedCrossRef
23.
go back to reference Levy, D., Kenchaiah, S., Larson, M. G., Benjamin, E. J., Kupka, M. J., Ho, K. K., et al. (2002). Long-term trends in the incidence of and survival with heart failure. The New England Journal of Medicine, 347, 1397–1402.PubMedCrossRef Levy, D., Kenchaiah, S., Larson, M. G., Benjamin, E. J., Kupka, M. J., Ho, K. K., et al. (2002). Long-term trends in the incidence of and survival with heart failure. The New England Journal of Medicine, 347, 1397–1402.PubMedCrossRef
24.
go back to reference Arroll, B., Doughty, R., & Andersen, V. (2010). Investigation and management of congestive heart failure. BMJ, 341, c3657.PubMedCrossRef Arroll, B., Doughty, R., & Andersen, V. (2010). Investigation and management of congestive heart failure. BMJ, 341, c3657.PubMedCrossRef
25.
go back to reference Benedict, C. R., Francis, G. S., Shelton, B., Johnstone, D. E., Kubo, S. H., Kirlin, P., et al. (1995). Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction. SOLVD Investigators. Am J Cardiol, 75, 1151–1157.PubMedCrossRef Benedict, C. R., Francis, G. S., Shelton, B., Johnstone, D. E., Kubo, S. H., Kirlin, P., et al. (1995). Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction. SOLVD Investigators. Am J Cardiol, 75, 1151–1157.PubMedCrossRef
26.
go back to reference Doughty, R. N., Whalley, G. A., Gamble, G., MacMahon, S., & Sharpe, N. (1997). Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. Journal of the American College of Cardiology, 29, 1060–1066.PubMedCrossRef Doughty, R. N., Whalley, G. A., Gamble, G., MacMahon, S., & Sharpe, N. (1997). Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. Journal of the American College of Cardiology, 29, 1060–1066.PubMedCrossRef
27.
go back to reference Di Biase, L., Gasparini, M., Lunati, M., Santini, M., Landolina, M., Boriani, G., et al. (2008). Antiarrhythmic effect of reverse ventricular remodeling induced by cardiac resynchronization therapy: the InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry. Journal of the American College of Cardiology, 52, 1442–1449.PubMedCrossRef Di Biase, L., Gasparini, M., Lunati, M., Santini, M., Landolina, M., Boriani, G., et al. (2008). Antiarrhythmic effect of reverse ventricular remodeling induced by cardiac resynchronization therapy: the InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry. Journal of the American College of Cardiology, 52, 1442–1449.PubMedCrossRef
28.
go back to reference Ypenburg, C., van Bommel, R. J., Borleffs, C. J., Bleeker, G. B., Boersma, E., Schalij, M. J., et al. (2009). Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. Journal of the American College of Cardiology, 53, 483–490.PubMedCrossRef Ypenburg, C., van Bommel, R. J., Borleffs, C. J., Bleeker, G. B., Boersma, E., Schalij, M. J., et al. (2009). Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. Journal of the American College of Cardiology, 53, 483–490.PubMedCrossRef
29.
go back to reference Dickstein, K., Vardas, P. E., Auricchio, A., Daubert, J. C., Linde, C., McMurray, J., et al. (2010). 2010 Focused Update of ESC guidelines on device therapy in heart failure: An update of the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. European Heart Journal, 3, 2677–2687. Dickstein, K., Vardas, P. E., Auricchio, A., Daubert, J. C., Linde, C., McMurray, J., et al. (2010). 2010 Focused Update of ESC guidelines on device therapy in heart failure: An update of the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. European Heart Journal, 3, 2677–2687.
30.
go back to reference Wells, G., Parkash, R., Healey, J. S., Talajic, M., Arnold, J. M., Sullivan, S., et al. (2011). Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials. CMAJ, 183, 421–429.PubMedCrossRef Wells, G., Parkash, R., Healey, J. S., Talajic, M., Arnold, J. M., Sullivan, S., et al. (2011). Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials. CMAJ, 183, 421–429.PubMedCrossRef
31.
go back to reference Cohn, J. N., Ferrari, R., & Sharpe, N. (2000). Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology, 35, 569–582.PubMedCrossRef Cohn, J. N., Ferrari, R., & Sharpe, N. (2000). Cardiac remodeling–concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology, 35, 569–582.PubMedCrossRef
32.
go back to reference Ghio, S., Freemantle, N., Scelsi, L., Serio, A., Magrini, G., Pasotti, M., et al. (2009). Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial. European Journal of Heart Failure, 11, 480–488.PubMedCrossRef Ghio, S., Freemantle, N., Scelsi, L., Serio, A., Magrini, G., Pasotti, M., et al. (2009). Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial. European Journal of Heart Failure, 11, 480–488.PubMedCrossRef
33.
go back to reference St John Sutton, M. G., Plappert, T., Abraham, W. T., Smith, A. L., DeLurgio, D. B., Leon, A. R., et al. (2003). Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation, 107, 1985–1990.PubMedCrossRef St John Sutton, M. G., Plappert, T., Abraham, W. T., Smith, A. L., DeLurgio, D. B., Leon, A. R., et al. (2003). Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation, 107, 1985–1990.PubMedCrossRef
34.
go back to reference Dickstein, K., Cohen-Solal, A., Filippatos, G., McMurray, J. J., Ponikowski, P., Poole-Wilson, P. A., et al. (2008). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). European Heart Journal, 29, 2388–2442.PubMedCrossRef Dickstein, K., Cohen-Solal, A., Filippatos, G., McMurray, J. J., Ponikowski, P., Poole-Wilson, P. A., et al. (2008). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). European Heart Journal, 29, 2388–2442.PubMedCrossRef
Metadata
Title
Cardiac resynchronization therapy in patients with mild heart failure: a systematic review and meta-analysis
Authors
Pasquale Santangeli
Luigi Di Biase
Gemma Pelargonio
Antonio Dello Russo
Michela Casella
Stefano Bartoletti
J. David Burkhardt
Prasant Mohanty
Pietro Santarelli
Andrea Natale
Publication date
01-11-2011
Publisher
Springer US
Published in
Journal of Interventional Cardiac Electrophysiology / Issue 2/2011
Print ISSN: 1383-875X
Electronic ISSN: 1572-8595
DOI
https://doi.org/10.1007/s10840-011-9584-y

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