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

Nolan et al.
European Journal of Cardiovascular Prevention & Rehabilitation

Special Introduction by the Authors

The analysis of heart rate variability (HRV) has been utilized in numerous prospective studies to assess prognosis for patients with coronary artery disease (CAD). Meta-analysis indicates that within the initial 2 years of recovery following myocardial infarction (MI), patients with diminished HRV are at increased risk for clinical events [1]. On the other hand, there is preliminary evidence that a treatment-induced increase in HRV among post-MI patients is independently associated with improved prognosis over a similar 2-year follow-up. [2]

To date, the use of HRV analysis to estimate prognosis among CAD patients has been almost exclusively based upon baseline assessments. Meanwhile, several clinical trials of secondary prevention strategies with CAD patients have reported HRV as a surrogate index of clinical outcome. Our aim in conducting a meta-analysis of these trials was to establish a standardized guide for interpreting the mean magnitude of HRV change following secondary prevention strategies with conventional drug therapy (ß-blockers, ACE inhibitors, CC blockers), biobehavioral treatments (psychotropic medications, biofeedback and relaxation training), and exercise training.

As noted in the meta-analysis that we present in this issue of EJCPR [3], secondary prevention strategies for CAD patients evoke a moderate increase in HRV, which is equivalent to an absolute increase in the standard deviation of normal R-R interval of 9.0 ms, or a relative increase of 15.9%. To detect HRV change of this magnitude, we estimate that a 2 parallel-group trial would require a sample size of 660 subjects for conventional drug treatment (ß-blockers, ACE inhibitors, CC blockers), while 1232 subjects would be required with the inclusion of biobehavioral treatments or exercise training. These findings provide a framework to assist a second generation of HRV trials that are designed to evaluate the independent contribution of HRV change to CAD prognosis.

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1. Bailey JJ, Berson AS, Handelsman H, Hodges M. Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction. JAm Coll Cardiol 2001; 38:1902-11.
2. Lampert R, Ickovics JR, Viscoli CJ, Horwitz RI, Lee FA. Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack Trial. Am J Cardiol 2003; 91:137-42.
3. Nolan RP, Jong P, Barry-Bianchi SM, Tanaka TH, Floras JS. Effects of drug, biobehavioral and exercise therapies on heart rate variability in coronary artery disease: a systematic review. Eur J Cardiovasc Prev Rehabil. 2008; 15 (4):386-396.

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