Clinical Investigation
Prevention and Rehabilitation
Quantitative electrocardiographic measures and long-term mortality in exercise test patients with clinically normal resting electrocardiograms

https://doi.org/10.1016/j.ahj.2009.04.015Get rights and content

Background

Currently, the only function of the resting electrocardiogram (ECG) in patients referred for exercise testing is to determine whether imaging is mandated. It is unknown if subtle ECG findings in those patients with clinically normal resting ECGs have prognostic significance.

Methods

We performed a single-center cohort study of 18,964 patients without known cardiovascular disease who had a clinically normal resting ECG and who underwent treadmill exercise testing for evaluation of suspected coronary artery disease. Eleven quantitative ECG measures relating to heart rate, conduction, left ventricular mass, or repolarization were collected digitally. The primary outcome was all-cause mortality. The prognostic importance of a composite ECG score was assessed by measuring its impact on the c-index (analogous to area under receiver operating characteristic curve) and by measures of reclassification.

Results

During a median follow-up of 10.7 years, 1,585 patients died. The 4 most predictive digital ECG variables were higher ventricular rate, more leftward QRS axis, more downward ST-segment deviation, and longer QT interval. The ECG score was independently associated with mortality (75th vs 25th percentile hazard ratio 1.36, 95% confidence interval 1.25-1.49, P < .0001). The ECG score had modest impact on discrimination (change in c-index 0.04) and reclassification of risk (3.0% decrease of relative integrated discrimination improvement, P < .001).

Conclusions

Subtle ECG findings relating to heart rate, conduction, left ventricular mass, or repolarization in patients with clinically normal ECGs referred for exercise testing may provide modest additional prognostic information over and above clinical and exercise measures.

Section snippets

Study population

We performed a single-center (Cleveland Clinic, Cleveland, OH) cohort study. Between September 1990 and December 2002, 46,966 patients without known CVD or end-stage renal disease, 30 years or older, were referred for symptom-limited treadmill exercise stress testing at our institution (Figure 1). None of the patients had known coronary disease (as defined by a history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting), heart failure, documented

Patient characteristics

There were 18,964 patients with both a qualitatively normal ECG and a digital 12-lead resting ECG file available for quantitative analysis; their characteristics are shown in Table I.

Among these 18,964 patients, 3,441 (18%) were on aspirin, 1,178 (6%) were on statins, 217 (1%) were on other antihypelipidemic medications, 1,529 (8%) were on thiazide diuretics, 1,968 (10%) were on β-blockers, 1,635 (9%) were on calcium-channel blockers, and 1,447 (8%) were on angiotensin-converting enzyme

Discussion

In this study of 18,964 patients without known CVD who were referred for exercise testing and who had a clinically normal resting ECG, we found that a number of digitally measured ECG findings reflective of heart rate, conduction, left ventricular mass, and repolarization were predictive of long-term mortality individually and as a composite. However, the increased risk associated with a composite ECG score led to a small change in the OOB c-index (4.8%), which suggested that adding information

Summary and conclusions

We found that the resting ECG done before exercise testing may provide incremental prognostic value beyond determining validity of ST-segment interpretation. Subtle ECG findings relating to heart rate, conduction, left ventricular mass, and repolarization portend a worse long-term prognosis but only modestly improve discrimination and clinical risk stratification for all-cause mortality.

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