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Eur J Cardiovasc Prev Rehabil. 2008 Aug;15(4):386-96. doi: 10.1097/HJR.0b013e3283030a97.

Effects of drug, biobehavioral and exercise therapies on heart rate variability in coronary artery disease: a systematic review.

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Division of Cardiology, University Health Network, Toronto, Ontario, Canada.



Heart rate variability (HRV) is reported as a surrogate index for clinical outcome in trials of secondary prevention strategies for coronary artery disease (CAD), but a standardized guide for interpreting HRV change is not established.


We evaluated HRV change in trials with CAD patients who received conventional medications (beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors), biobehavioral treatment (psychotropics, biofeedback, relaxation) or exercise training.


Medline, Pubmed, Psycinfo, the Cochrane database, and Embase were searched until July 2007, without language restriction. We identified 33 randomized controlled trials. Two reviewers independently abstracted all trials using a standardized form. A hierarchy of frequency and time domain HRV indices defined outcome.


A random-effects model yielded an overall pooled standardized mean difference (SMD) between treatment and control groups of moderate magnitude across treatment classes, based on a composite of time and frequency domain indices (SMD=0.40, P<0.0001), or only time or frequency indices (SMD=0.37 and 0.43, respectively, both P<0.0001). This change was equivalent to an increase in standard deviation of all normal-to-normal RR intervals of 9.0 ms (95% Confidence Interval, CI, 7.3, 10.7 ms) or a relative increase of 15.9% (95% CI, 13.2, 18.6%). To detect HRV change of this magnitude, a hypothetical trial would require a sample size of 660 patients for conventional medications or 1232 patients for all treatment classes.


Pharmacologic, biobehavioral and exercise strategies for secondary prevention of CAD significantly increase HRV. This review provides a framework to assist efforts to evaluate the contribution of HRV change to CAD prognosis.

[Indexed for MEDLINE]

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