Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Cardiac resynchronization therapy reduces mortality and hospitalization for heart failure


ACP J Club. 2005 Mar-Apr;142:35. doi:10.7326/ACPJC-2005-142-2-035

Clinical Impact Ratings

Cardiology: 5 stars

Cardiology: 5 stars

Source Citations

McAlister FA, Ezekowitz JA, Wiebe N, et al. Systematic review: cardiac resynchronization in patients with symptomatic heart failure. Ann Intern Med. 2004;141:381-90. [PubMed ID: 15353430]

Nichol G, Kaul P, Huszti E, Bridges JF. Cost-effectiveness of cardiac resynchronization therapy in patients with symptomatic heart failure. Ann Intern Med. 2004;141:343-51. [PubMed ID: 15353425]



In patients with symptomatic heart failure (HF), how effective is cardiac resynchronization therapy (CRT)?


Data sources: Cochrane Library, MEDLINE, EMBASE/Excerpta Medica, Web of Science, several trial registries, primary authors of included studies, FDA reports, reference lists of included studies, and companies that produce biventricular devices up to May 2004.

Study selection and assessment: Randomized controlled trials (RCTs) of CRT in patients with symptomatic HF. Health-related quality of life (QOL) and cost data were gathered from publicly available data.

Outcomes: All-cause mortality, hospitalization for HF, or both. Secondary outcomes were HF mortality, overall cardiac mortality, noncardiac mortality, 6-minute walk test, improvement in New York Heart Association (NYHA) class, and QOL. The economic analysis determined incremental cost per quality-adjusted life-year (QALY) using 2003 U.S. dollars . The willingness-to-pay threshold was $100 000/QALY.

Main results

9 RCTs (n = 3574, mean age 64 y, 74% men, all had prolonged QRS durations and left ventricular ejection fraction < 35%) were included. 10 additional cohort studies were included in a safety analysis. Most patients were receiving angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Fewer patients who received CRT died from any cause or had hospitalization for HF than did patients who received control treatment (Table). CRT was associated with an increase in 6-minute walk distance (8 RCTs, weighted mean difference 28 m, 95% CI 16 to 40), improvement in ≥ 1 NYHA class (4 RCTs, relative risk 1.6, CI 1.3 to 1.9), and improvement in QOL (7 RCTs, 7.6-point improvement on Minnesota Living with Heart Failure Questionnaire, CI 3.8 to 11.5). The periimplantation mortality rate was low (0.4%). The median incremental cost-effectiveness of CRT was $107 800/QALY (interquartile range 79 800 to 156 500).


In patients with systolic heart failure and evidence of electromechanical dyssynchrony who remain symptomatic despite optimal pharmacotherapy, cardiac resynchronization therapy (CRT) reduces all-cause mortality and heart failure hospitalization and improves quality of life and functional status.

Sources of funding: Dr. McAlister: Agency for Healthcare Research and Quality; Alberta Heritage Foundation for Medical Research; Canadian Institutes of Health Research; University of Alberta Merck Frosst/Aventis Patient Health Management Chair. Dr. Nichol: Agency for Healthcare Research and Quality and Heart and Stroke Foundation of Canada.

For correspondence: Dr. F.A. McAlister, University of Alberta Hospital, Edmonton, Alberta, Canada. E-mail Dr. G. Nichol, University of Washington-Harborview Prehospital Research and Training Center, Seattle, WA, USA. E-mail

Table. Cardiac resynchronization therapy vs control for symptomatic heart failure*

Outcomes Number of trials RRR (95% CI) NNT (CI)
All-cause mortality 9 21% (4 to 34) 24 (15 to 124)†
Heart failure hospitalization 6 33% (8 to 52) 16 (9 to 56)

*Control treatment was usually a pacemaker turned off. Follow-up ranged from 1 to 12 months. Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article using a random-effects model. All outcomes favor cardiac resynchronization therapy.
†Data provided by author.


The reviews by McAlister and Nichol and their colleagues provide a helpful construct for discussing the financial analysis of biventricular (BiV) pacing. BiV is a costly but effective alternative for patients in whom all currently available medical treatments have failed. The authors estimated a conservative $30 000/patient; however, most BiV implants in the United States are now coupled with an implantable defibrillator (ICD), resulting in a cost often in excess of $50 000. Many of the trials in the review by McAlister and colleagues used less expensive and possibly less effective BiV pacemakers. Previous RCTs of ICDs showed a benefit in most patients with decreased left ventricular function (1, 2). The MIRACLE trial (3) showed a 77% reduction in the number of days hospitalized for CHF with CRT, a difference that will likely translate into a lower cost per hospital visit. This cost differential and the financial effects of CRT on office visits are difficult to quantify and were not included in the analysis by Nichol and colleagues.

Most of the cost associated with BiV implants occurs at implantation. The devices can be maintained at minimal cost with long-lasting batteries. However, device-related complications incur additional costs. Many studies had only 6-month follow-up, making long-term cost estimates challenging. Longer studies are required to determine whether benefits of BiV pacing will increase with minimal incremental cost in years 2 to 6.

The implantation of resynchronization devices is a highly technical procedure. The leads and delivery systems currently available dramatically improve implant success and shorten procedure duration. These improvements have theoretical but unproven effects on periprocedural complication rates, efficacy, and lead dislodgement rate. An intention-to-treat comparison of costs of modern resynchronization equipment would certainly assist in patient selection for CRT.

McAlister and Nichol and their colleagues help us ponder whether patients with end-stage HF should be resynchronized at high cost or have therapy limited by cost and remain symptomatic until they die.

Andrew Corsello, MD
Cardiovascular Consultants of Maine
Scarborough, Maine, USA


1. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-83. [PubMed ID: 11907286]

2. Bardy GH, Lee KL, Mark DB, et al. Sudden Cardiac Death-Health Failure Trial. American College of Cardiology Annual Scientific Session. New Orleans, March 2004.

3. Abraham WT, Fisher WG, Smith AL, et al. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346:1845-53. [PubMed ID: 12063368]