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CLINICAL STUDY: STRESS TESTING

Statistical methods to improve the precision of the treadmill exercise test

Ralph A. H. Stewart, MD, FRACP^*, John Kittelson, PhD and I. Patrick Kay, FRACP^*

^* Department of Medicine, University of Otago, Dunedin, New Zealand
Department of Social and Preventive Medicine, University of Otago, Dunedin, New Zealand

Manuscript received December 20, 1999; revised manuscript received March 27, 2000, accepted June 1, 2000.

Reprint requests and correspondence: Dr. Ralph Stewart, CCU Research Suite, Green Lane Hospital, Private Bag 92 189, Auckland 1030, New Zealand
rstewart{at}ahsl.co.nz

OBJECTIVES

The study systematically compared different measures of ST segment depression from the treadmill exercise test.

BACKGROUND

The value of the treadmill exercise test for objectively measuring treatment effects is limited by random error in the measurement of ST depression and may be biased by regression to the mean or by the decision to terminate the test.

METHODS

Treadmill exercise was performed in 21 subjects with ischemic heart disease 1 h after isosorbide dinitrate 10 mg or placebo in a double-blind randomized crossover study. A 12-lead electrocardiogram (ECG) was recorded every 30 s during and at peak exercise. The relative sample size needed to detect the nitrate effect was compared for different summary measures of ST depression.

RESULTS

The ST depression measured from a single unmatched lead at longest equivalent sub-maximal exercise needed the lowest sample size to detect the nitrate effect in paired comparisons (p = 0.000006). Averaging over multiple leads or times did not improve detection of the nitrate effect. The rate of increase in ST depression (in mm/min) calculated by linear regression needed a similar sample size (x1.32, 95% CI 0.62 to 2.58). A larger sample size was needed for ST depression at peak exercise (x2.9, CI 1.3, 11.1) and exercise duration (x4.5, CI 1.5, 38). Time to 1-mm ST depression was the least efficient measurement (relative sample size x15.5, CI 1.6, >1000). Comparison of matched leads resulted in >2-fold differences in estimates of the nitrate effect because of bias from regression to the mean.

CONCLUSIONS

Maximal ST depression at longest equivalent sub-maximal exercise and the maximal rate of increase in ST depression had less bias and random variation than did other commonly used measures. The rate of increase in ST depression is preferred because it can be calculated in either paired or unpaired studies.

Abbreviations and Acronyms   ACC = American College of Cardiology   AHA = American Heart Association   ECG = electrocardiogram

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