An Externally Validated Model for Predicting Long-Term Survival after Exercise Treadmill Testing in Patients with Suspected Coronary Artery Disease and a Normal Electrocardiogram

18 December 2007 | Volume 147 Issue 12 | Pages 821-828

Background: The exercise treadmill test is recommended for risk stratification among patients with intermediate to high pretest probability of coronary artery disease. Posttest risk stratification is based on the Duke treadmill score, which includes only functional capacity and measures of ischemia.

Objective: To develop and externally validate a post–treadmill test, multivariable mortality prediction rule for adults with suspected coronary artery disease and normal electrocardiograms.

Design: Prospective cohort study conducted from September 1990 to May 2004.

Setting: Exercise treadmill laboratories in a major medical center (derivation set) and a separate HMO (validation set).

Patients: 33 268 patients in the derivation set and 5821 in the validation set. All patients had normal electrocardiograms and were referred for evaluation of suspected coronary artery disease.

Measurements: The derivation set patients were followed for a median of 6.2 years. A nomogram-illustrated model was derived on the basis of variables easily obtained in the stress laboratory, including age; sex; history of smoking, hypertension, diabetes, or typical angina; and exercise findings of functional capacity, ST-segment changes, symptoms, heart rate recovery, and frequent ventricular ectopy in recovery.

Results: The derivation data set included 1619 deaths. Although both the Duke treadmill score and our nomogram-illustrated model were significantly associated with death (P < 0.001), the nomogram was better at discrimination (concordance index for right-censored data, 0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate- to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The model also predicted 3-year mortality rates well in the validation set: Based on an optimal cut-point for a negative predictive value of 0.97, derivation and validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25% and 29% above the cut-point.

Limitations: Blood test–based measures or left ventricular ejection fraction were not included. The nomogram can be applied only to patients with a normal electrocardiogram. Clinical utility remains to be tested.

Conclusion: A simple nomogram based on easily obtained pretest and exercise test variables predicted all-cause mortality in adults with suspected coronary artery disease and normal electrocardiograms.

Editors' Notes Context How might we best stratify low-risk patients with normal electrocardiograms but suspected coronary artery disease? Contribution This large prospective study evaluated a post–treadmill test mortality prediction rule in adults with normal electrocardiograms and suspected coronary artery disease. A nomogram that included clinical variables (age, sex, smoking, and diabetes) and treadmill variables (exercise capacity, abnormal heart rate recovery, and ventricular ectopy during recovery) better identified patients with less than a 3% mortality rate over 3 years than did a standard Duke treadmill score. Implication The nomogram warrants additional validation to verify that it reliably identifies low-risk patients who need no further cardiac work-up after a treadmill test. —The Editors

 

Author and Article Information

From the Cleveland Clinic Foundation, Cleveland, Ohio; National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Kaiser Permanente Colorado, Denver, Colorado.

Acknowledgment: The authors thank Ethan Katz and Susana Arrigain for their help with statistical analyses.

Grant Support: By the National Heart, Lung, and Blood Institute (grants NHLBI HL66004 and HL072771).

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: Statistical code is available by contacting Dr. Lauer at lauerm{at}nhlbi.nih.gov. The study protocol and data set are not available.

Requests for Single Reprints: Michael S. Lauer, MD, Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Bethesda, MD 20892; e-mail, lauerm{at}nhlbi.nih.gov.

Current Author Addresses: Dr. Lauer: Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Bethesda, MD 20892.

Ms. Pothier: Cleveland Clinic, 9500 Euclid Avenue, JJ5-801, Cleveland, OH 44195.

Dr. Magid: Kaiser Permanente, 10065 East Harvard Avenue, Suite 300, Denver, CO 80231.

Dr. Smith: Kaiser Permanente, 10350 East Dakota Avenue, Denver, CO 80247.

Dr. Kattan: Cleveland Clinic, 9500 Euclid Avenue, Wb4, Cleveland, OH 44195.

Author Contributions: Conception and design: M.S. Lauer.

Analysis and interpretation of the data: M.S. Lauer, D.J. Magid, M.W. Kattan.

Drafting of the article: M.S. Lauer, M.W. Kattan.

Critical revision of the article for important intellectual content: M.S. Lauer, C.E. Pothier, D.J. Magid, S.S. Smith, M.W. Kattan.

Final approval of the article: M.S. Lauer, D.J. Magid, M.W. Kattan.

Provision of study materials or patients: M.S. Lauer.

Statistical expertise: M.S. Lauer, M.W. Kattan.

Obtaining of funding: M.S. Lauer.

Collection and assembly of data: C.E. Pothier.

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