Economic Evaluation of Cardiac Contractility Modulation (CCM) Therapy with the Optimizer IVs in the Management of Heart Failure Patients


  • Nikos Maniadakis National School of Public Health
  • Vasilios Fragoulakis Department of Health Services Organisation & Management, National School of Public Health, Athens, GR
  • Charalambos Mylonas Department of Health Services Organisation & Management, National School of Public Health, Athens, GR
  • Rakesh Sharma Royal Brompton Hospital, London
  • Andrew Stewart Coats Monash University, Australia and University of Warwick, UK



Heart Failure, Cardiac Contractility Modulation, Optimizer, Economic Evaluation, Cost Effectiveness Analysis, Cost Utility Analysis


Background: Heart failure represents a major burden for health systems and societies. Cardiac contractility modulation (CCM) therapy was developed in recent years for patients with normal QRS in whom optimal pharmacological (OMT) treatment has failed to control symptoms adequately. This study presents an economic evaluation of CCM therapy for the UK.

Methods: A Markov model was built to simulate the management of patients under two therapy scenarios, on OMT alone and CCM+OMT respectively. The horizon is the patient’s life time and the cycle is 4 weeks. The model estimates life year (LYs), quality adjusted life years (QALYs) and overall treatment costs. Data to populate it came from relevant CCM trials, the literature and other sources.

Results: The total mean life-time cost was £37,467 in the CCM+OMT arm and £16,885 in the OMT arm. Patients in the OMT arm gained 7.00 LYs and 4.00 QALYs and those on CCM+OMT 7.96 and 5.26 respectively. The incremental cost per QALY was £16,405and the incremental cost per LY £21,415. Sensitivity analysis indicates that the results are pretty stable and stochastic analysis indicates that at a £30,000 per QALY threshold the likelihood of CCM+OMT being cost-effective is 99.8% and at £25,000 per QALY 97%.

Conclusion: The present analysis indicates that CCM may be cost-effective therapy. This early conclusion should be viewed in the light of the caveats of the modeling methods used, due to data availability.  Long-term studies directly collecting hospitalization and mortality data should be undertaken to provide more robust evidence.


McMurray, J.J., et al., 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 Heart J, 2012. 33(14): p. 1787-847. doi: 10.1093/eurjhf/hfs105.

(NICE), Chronic heart failure: the management of chronic heart failure in adults in primary and secondary care. . NICE Clinical Guidance No 108. 2010., 2010. London: National Clinical Guideline Centre. Available from:

Lindenfeld, J., et al., HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail, 2010. 16(6): p. e1-194. doi: 10.1016/j.cardfail.2010.04.004

Bleumink, G.S., et al., Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J, 2004. 25(18): p. 1614-9. DOI:

Bundkirchen, A. and R.H. Schwinger, Epidemiology and economic burden of chronic heart failure European Heart Journal Supplements 2004. 6(Supplement D): p. 57-60. DOI:

Zannad, F., N. Agrinier, and F. Alla, Heart failure burden and therapy. Europace, 2009. 11 Suppl 5: p. v1-9.

Braunschweig, F., M.R. Cowie, and A. Auricchio, What are the costs of heart failure? Europace, 2011. 13 Suppl 2: p. ii13-7. DOI:

Komajda, M., et al., The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J, 2003. 24(5): p. 464-74. DOI:

Cleland, J.G., et al., The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J, 2003. 24(5): p. 442-63. DOI:

Maggioni, A.P., et al., Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail, 2013. 15(10): p. 1173-84. doi: 10.1093/eurjhf/hft134

Beshai, J.F., et al., Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med, 2007. 357(24): p. 2461-71. DOI: 10.1056/NEJMoa0706695

Ruschitzka, F., et al., Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med, 2013. 369(15): p. 1395-405. doi: 10.1056/NEJMoa1306687

Borggrefe, M. and D. Burkhoff, Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure. Eur J Heart Fail, 2012. 14(7): p. 703-12. doi: 10.1093/eurjhf/hfs078

Kuck, K.H., et al., New devices in heart failure: an European Heart Rhythm Association report: developed by the European Heart Rhythm Association; endorsed by the Heart Failure Association. Europace, 2014. 16(1): p. 109-28. doi: 10.1093/europace/eut311

Winter, J., K.E. Brack, and G.A. Ng, Cardiac contractility modulation in the treatment of heart failure: initial results and unanswered questions. Eur J Heart Fail, 2011. 13(7): p. 700-10. doi: 10.1093/eurjhf/hfr042

Borggrefe, M.M., et al., Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J, 2008. 29(8): p. 1019-28. doi: 10.1093/eurheartj/ehn020

Neelagaru, S.B., et al., Nonexcitatory, cardiac contractility modulation electrical impulses: feasibility study for advanced heart failure in patients with normal QRS duration. Heart Rhythm, 2006. 3(10): p. 1140-7. DOI:

Kadish, A., et al., A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J, 2011. 161(2): p. 329-337 e1-2. doi: 10.1016/j.ahj.2010.10.025

Giallauria, F., et al., Effects of cardiac contractility modulation by non-excitatory electrical stimulation on exercise capacity and quality of life: an individual patient's data meta-analysis of randomized controlled trials. Int J Cardiol, 2014. 175(2): p. 352-7. doi: 10.1016/j.ijcard.2014.06.005

Kwong, J.S., J.E. Sanderson, and C.M. Yu, Cardiac contractility modulation for heart failure: a meta-analysis of randomized controlled trials. Pacing Clin Electrophysiol, 2012. 35(9): p. 1111-8. doi: 10.1111/j.1540-8159.2012.03449.x

Abraham, W.T., et al., Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. J Card Fail, 2011. 17(9): p. 710-7. doi: 10.1016/j.cardfail.2011.05.006

Levy, W.C., et al., The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation, 2006. 113(11): p. 1424-33. DOI: 10.1161/CIRCULATIONAHA.105.584102

Mozaffarian, D., et al., Prediction of mode of death in heart failure: the Seattle Heart Failure Model. Circulation, 2007. 116(4): p. 392-8. DOI: 10.1161/CIRCULATIONAHA.106.687103

Ahmed, A., W.S. Aronow, and J.L. Fleg, Higher New York Heart Association classes and increased mortality and hospitalization in patients with heart failure and preserved left ventricular function. Am Heart J, 2006. 151(2): p. 444-50. DOI:

Cleland J., D.H., Hardman S., McDonagh T., Mitchell P., National Heart Failure Audit, April 2012 - March 2013. NICOR (National Institute for Cardiovascular Outcomes Research) and The British Society for Heart Failure (BSH), 2013(

Schau, T., et al., Long-term outcome of cardiac contractility modulation in patients with severe congestive heart failure. Europace, 2011. 13(10): p. 1436-44. doi: 10.1093/europace/eur153

Fox, M., et al., The clinical effectiveness and cost-effectiveness of cardiac resynchronisation (biventricular pacing) for heart failure: systematic review and economic model. Health Technol Assess, 2007. 11(47): p. iii-iv, ix-248. DOI:

Calvert, M.J., N. Freemantle, and J.G. Cleland, The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail, 2005. 7(2): p. 243-51. Eur J Heart Fail, 2005. 7(2): p. 243-51

Griffiths, A., et al., The cost effectiveness of ivabradine in the treatment of chronic heart failure from the U.K. National Health Service perspective. Heart, 2014. 100(13): p. 1031-6. doi: 10.1136/heartjnl-2013-304598

NHS, National Schedule of Reference Costs Year : 2010-11 - NHS Trusts HRG Data. 2014.

Unit Costs of Health and Social Care 2013. Personal Social Services Research Unit, Cornwallis Building, The University of Kent, Canterbury, Kent CT2 7NF.

Goehler, A., et al., Decision-analytic models to simulate health outcomes and costs in heart failure: a systematic review. Pharmacoeconomics, 2011. 29(9): p. 753-69. doi: 10.2165/11585990-000000000-00000

Rolandi, E., et al., Long-term therapy of chronic congestive heart failure with ibopamine: a multicenter trial. J Cardiovasc Pharmacol, 1989. 14 Suppl 8: p. S93-103.

Ahmed, A., W.S. Aronow, and J.L. Fleg, Predictors of mortality and hospitalization in women with heart failure in the Digitalis Investigation Group trial. Am J Ther, 2006. 13(4): p. 325-31.

Ahmed, A., A propensity matched study of New York Heart Association class and natural history end points in heart failure. Am J Cardiol, 2007. 99(4): p. 549-53. DOI:

Ahmed, A., et al., A propensity-matched study of the effects of chronic diuretic therapy on mortality and hospitalization in older adults with heart failure. Int J Cardiol, 2008. 125(2): p. 246-53. DOI:

Borer, J.S., et al., Efficacy and safety of ivabradine in patients with severe chronic systolic heart failure (from the SHIFT study). Am J Cardiol, 2014. 113(3): p. 497-503. doi: 10.1016/j.amjcard.2013.10.033

Muntwyler, J., et al., One-year mortality among unselected outpatients with heart failure. Eur Heart J, 2002. 23(23): p. 1861-6. doi:10.1053/euhj.2002.3282

Bouvy, M.L., et al., Predicting mortality in patients with heart failure: a pragmatic approach. Heart, 2003. 89(6): p. 605-9. doi:10.1136/heart.89.6.605

Gheorghiade, M., et al., Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail, 2013. 15(5): p. 551-9. DOI: 10.1093/eurjhf/hft010

Lindenfeld, J., et al., Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation, 2007. 115(2): p. 204-12. DOI: 10.1161/CIRCULATIONAHA.106.629261

Pocock, S.J., et al., Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J, 2013. 34(19): p. 1404-13. doi: 10.1093/eurheartj/ehs337

Cowie, M.R., et al., Survival of patients with a new diagnosis of heart failure: a population based study. Heart, 2000. 83(5): p. 505-10. doi:10.1136/heart.83.5.505

Cowie, M.R., et al., Hospitalization of patients with heart failure: a population-based study. Eur Heart J, 2002. 23(11): p. 877-85. doi:10.1053/euhj.2001.2973

Cleland, J.G., et al., Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J, 2009. 157(3): p. 457-66. doi: 10.1016/j.ahj.2008.11.006

Anand, I.S., et al., Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial. Circulation, 2009. 119(7): p. 969-77. doi: 10.1161/CIRCULATIONAHA.108.793273

Ouwerkerk, W., A.A. Voors, and A.H. Zwinderman, Factors Influencing the Predictive Power of Models for Predicting Mortality and/or Heart Failure Hospitalization in Patients With Heart Failure. JACC Heart Fail, 2014. 2(5): p. 429-436. doi:10.1016/j.jchf.2014.04.006

van Hout, B.A., et al., Effects of ACE inhibitors on heart failure in The Netherlands: a pharmacoeconomic model. Pharmacoeconomics, 1993. 3(5): p. 387-97.

Glick, H.A., et al., Economic evaluation of the randomized aldactone evaluation study (RALES): treatment of patients with severe heart failure. Cardiovasc Drugs Ther, 2002. 16(1): p. 53-9.

Glick, H., et al., Costs and effects of enalapril therapy in patients with symptomatic heart failure: an economic analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial. J Card Fail, 1995. 1(5): p. 371-80.

Cook, J.R., et al., The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction. Am J Hypertens, 1998. 11(12): p. 1433-41.

Yao, G., et al., The long-term cost-effectiveness of cardiac resynchronization therapy with or without an implantable cardioverter-defibrillator. Eur Heart J, 2007. 28(1): p. 42-51. DOI:

Miller, G., et al., Long-term cost-effectiveness of disease management in systolic heart failure. Med Decis Making, 2009. 29(3): p. 325-33. doi: 10.1177/ 0272989X08327494

Cowper, P.A., et al., Economic effects of beta-blocker therapy in patients with heart failure. Am J Med, 2004. 116(2): p. 104-11. DOI:

Banz, K., Cardiac resynchronization therapy (CRT) in heart failure--a model to assess the economic value of this new medical technology. Value Health, 2005. 8(2): p. 128-39. DOI: 10.1111/j.1524-4733.2005.03092.x

Francis, D.P., et al., Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO(2)slope and peak VO(2). Eur Heart J, 2000. 21(2): p. 154-61. DOI:

Myers, J., et al., Validation of a cardiopulmonary exercise test score in heart failure. Circ Heart Fail, 2013. 6(2): p. 211-8. DOI: 10.1161/CIRCHEARTFAILURE.112.000073

Flynn, K.E., et al., Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA, 2009. 301(14): p. 1451-9. doi: 10.1001/jama.2009.457

Blumenthal, J.A., et al., Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial. JAMA, 2012. 308(5): p. 465-74. doi:10.1001/jama.2012.8720

Swank, A.M., et al., Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail, 2012. 5(5): p. 579-85. DOI: 10.1161/CIRCHEARTFAILURE.111.965186

Alla, F., et al., Self-rating of quality of life provides additional prognostic information in heart failure. Insights into the EPICAL study. Eur J Heart Fail, 2002. 4(3): p. 337-43.

Ingle, L., et al., Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure. Heart, 2014. 100(10): p. 781-6. doi: 10.1136/heartjnl-2013-304614

Ingle, L., J.G. Cleland, and A.L. Clark, The long-term prognostic significance of 6-minute walk test distance in patients with chronic heart failure. Biomed Res Int, 2014. 2014: Article ID: 505969.

Arena, R., et al., Influence of subject effort on the prognostic value of peak VO2 and the VE/VCO2 slope in patients with heart failure. J Cardiopulm Rehabil, 2004. 24(5): p. 317-20. DOI: 10.1097/00008483-200409000-00006

Arena, R., et al., Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison. Am Heart J, 2004. 147(2): p. 354-60. DOI:

Kuschyk J, Roeger S, Schneider R, et al. Efficacy and survival in patients with cardiac contractility modulation: Long-term single center experience in 81 patients. Int J Cardiol. 2015;183C:76-81. DOI: 10.1016/j.ijcard.2014.12.178

Shewan L.G., Coats A.J.S., Henein M. Requirements for Ethical Publishing in Biomedical Journals. International Cardiovascular Forum Journal. 2015;2:2.


Additional Files





Original Article