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

Michael S. Lauer, MD; Claire E. Pothier, MPH; David J. Magid, MD, MPH; S. Scott Smith, MD; and Michael W. Kattan, PhD
[+] Article, Author, and Disclosure 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@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@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.

Ann Intern Med. 2007;147(12):821-828. doi:10.7326/0003-4819-147-12-200712180-00001
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Analyzing the outcomes of a large cohort of more than 30 000 patients with suspected coronary artery disease and a normal electrocardiogram, we developed and externally validated a nomogram-illustrated model for predicting all-cause mortality. This model incorporates pretest variables that can be easily obtained in a stress laboratory without any need for blood tests or previous medical records (56). Our model also takes advantage of recent advances in our understanding of the prognostic value of stress testing by including heart rate recovery (89) and ventricular ectopy during recovery (12). The model performs substantially better than the Duke treadmill score both in discrimination (c-index, 0.83 vs. 0.73; P < 0.001) and calibration (Figures 2 and 4), even when penalized for its derivation from an internal data set.

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Figure 1.
Survival according to the Duke treadmill exercise score.

Values below the graph are patients at risk for death each year, after accounting for previous deaths and censoring.

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Figure 2.
Calibration plot for the Duke treadmill exercise score based on 10-fold cross-validation.

Patients are divided into deciles of predicted risk. The 45° line represents an ideal treadmill exercise score with perfect prediction. Vertical bars represent 95% CIs.

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Figure 3.
Nomogram of multivariable proportional hazards prediction model for all-cause mortality.

To determine risk, draw a vertical line from each risk marker to the top line, labeled “POINTS,” to calculate points for each risk marker. The sum of all these points is then marked on the line labeled “TOTAL POINTS.” Drop vertical lines from there to yield the 3- and 5-year survival probabilities. For binary variables, 1 means yes and 0 means no. MET = metabolic equivalent.

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Figure 4.
Calibration curve for 10-year nomogram prediction based on 10-fold cross-validation.

Patients are divided into deciles of predicted risk. The 45° line represents an ideal nomogram with perfect prediction. The vertical bars represent 95% CIs.

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Figure 5.
Three-year mortality rates in the derivation and validation data sets.

Multivariable model cut-point yields a negative predictive value of 0.97 in the derivation data set.

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In Defense of the Value of the History Taken from Patients with Chest Pain
Posted on January 18, 2008
William H Carter, MD, FACC
West Virginia University, Charleston Division
Conflict of Interest: None Declared

The excellent article by Lauer evaluating clinical predictors of survival after stress testing further refines the predictive value of exercise treadmill testing beyond that of the valuable Duke Treadmill Score.1 However, we are concerned that some readers will assume that a history of typical angina has no clinical value, an assumption we doubt Lauer et al meant to imply.

The study found no correlation with the history of typical angina versus other types of chest pain with the future survival. The authors correctly noted prior conflicting studies including a report by many of the same authors of the above report.2

A typical history of angina depends on how the history is taken. Open ended questions are known to lead to more valid conclusions compared to leading questions.3 The questions in the current study were all leading questions versus open ended questions. "Is the pain or discomfort substernal?" vs. "Where is the pain?". "Is the pain or discomfort brought on by physical activity or emotional stress?" vs. "What causes the pain?", etc. Would the findings of the prognostic value of the history been different had open ended questions been asked?

The Diamond/Forrester study and the combined CASS and Duke Database all demonstrate the strong predictive value of the history in predicting the presence of coronary disease, (versus all cause mortality at five years), and have been incorporated. Thus we should keep in perspective the findings of this study considering the (1) methodology of taking the chest pain history and (2) the totality of prior evidence supporting the clinical value of the history in the chest pain patientsepeatedly in stress testing guidelines.4

1. Lauer MS,. Pothier CE, Magid DJ, MD, Smith SS, Kattan MW, An Externally Validated Model for Predicting Long-Term Survival after Exercise Treadmill Testing in Patients with Suspected Coronary Artery Disease and a Normal Electrocardiogram. Ann Internal medicine: 2007, 147:821-828

2. Jones RC, Pothier CE, Blackstone EH, Lauer MS,: Prognostic Importance of Presenting Symptoms in Patients Undergoing Exercise Testing for Evaluation of Known or Suspected Coronary Disease., Am J Med. 2004;117:380 "“389.

3. Roter, DL Physicians Interviewing Styles and Medical Information Obtained from Patients. Journal of General Internal Medicine; Vol. 2, 1987:325-329.

4. ACC/AHA 2002 Guideline Update for the Management of Patients with Chronic

Stable Angina: J Am Coll Cardiol, 2003; 41: 159-68 (full text of guidelines www.acc.org pg 13)

Did treatment of positive tests obscure prediction?
Posted on January 29, 2008
D. Scott Grubbs
St. Francis Hospital System
Conflict of Interest: None Declared

Dr. Lauer, et al have published a very intriguing study, which seems to corroborate others in many respects. I wonder, however, if the fact that ST segment changes and anginal symptoms during the test have negative correlation might indicate something else.

There is no indication that I can find that this was simply an observational study, with the subjects sent home to usual care regardless of the test findings. I suspect that those patients who demonstrated those classically positive changes went on to catheterization and other interventions and therefore avoided cardiac events that would have otherwise caused a positive correlation.

Absent assurance that this was not the case, I would be very hesitant to employ the nomogram (as least pertaining to ST and Angina) the next time I encounter them doing a stress test.

Conflict of Interest:

None declared

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