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Implications of Abnormal Exercise Electrocardiography With Normal Stress Echocardiography

Educational Objective
To determine whether patients with positive exercise electrocardiography (ECG) and normal stress Echo imaging (+ECG/−Echo) have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (−ECG/−Echo).
1 Credit CME
Key Points

Question  What are the clinical implications and prognostic significance of abnormal (positive) exercise electrocardiography but normal stress echocardiography?

Findings  In this cohort study including 15 077 patients undergoing exercise stress echocardiography for suspected coronary artery disease, positive exercise electrocardiography but normal stress echocardiography was associated with higher rates of short- and long-term adverse cardiac events compared with negative exercise electrocardiography and normal stress echocardiography.

Meaning  Abnormal exercise electrocardiography but normal stress echocardiography may identify patients at a slightly increased cardiac risk that was not previously recognized.


Importance  Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/−Echo) are commonly encountered in clinical practice; however, the prognostic significance of this discordant result is unclear.

Objective  To determine whether patients with +ECG/−Echo have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (−ECG/−Echo).

Design, Setting, and Participants  Between January 1, 2000, and February 28, 2014, a total of 47 944 consecutive patients without known coronary artery disease who underwent exercise stress Echo at Duke University Medical Center were evaluated for inclusion in this observational cohort study. Data analysis was conducted from January 1, 2000, to December 31, 2016.

Interventions/Exposures  Patients were categorized as having −ECG/−Echo, +ECG/−Echo, or +Echo (−ECG/+Echo and +ECG/+Echo).

Main Outcomes and Measures  The primary outcome was a composite end point of death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary outcomes included individual adverse events and downstream testing.

Results  After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results. Of these, 12 893 patients (85.5%) had −ECG/−Echo, 1286 patients (8.5%) had +ECG/−Echo, and 898 patients (6.0%) had +Echo. Through a median follow-up of 7.3 (interquartile range, 4.4-10.0) years, the composite end point occurred in 794 patients with −ECG/−Echo (8.5%), 142 patients with +ECG/−Echo (14.6%), and 297 patients with +Echo (37.4%). Death occurred in 425 patients with −ECG/−Echo (4.8%), 50 patients with +ECG/−Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with −ECG/−Echo (2.2%), 31 patients with +ECG/−Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with −ECG/−Echo imaging results had the least downstream testing (2.3%), followed by +ECG/−Echo (12.8%), and +Echo (33.6%) (P < .001).

Conclusions and Relevance  The presence of +ECG results with normal stress Echo imaging may identify a population of patients who are at slightly increased risk for adverse cardiac events, which was not previously recognized. Further study is needed to determine whether these patients will benefit from intensification of medical management.

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Article Information

Accepted for Publication: November 30, 2019.

Corresponding Author: Melissa A. Daubert, MD, Duke Clinical Research Institute, 200 Morris St, Durham, NC 27701 (

Published Online: January 27, 2020. doi:10.1001/jamainternmed.2019.6958

Author Contributions: Dr Daubert had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Daubert, Sivak, Wang, Velazquez.

Acquisition, analysis, or interpretation of data: Daubert, Sivak, Dunning, Douglas, Coyne, Mark, Velazquez.

Drafting of the manuscript: Daubert, Sivak.

Critical revision of the manuscript for important intellectual content: Dunning, Douglas, Coyne, Wang, Mark, Velazquez.

Statistical analysis: Sivak, Dunning.

Obtained funding: Velazquez.

Administrative, technical, or material support: Daubert, Coyne, Velazquez.

Supervision: Daubert, Mark, Velazquez.

Conflict of Interest Disclosures: Dr Mark reported receiving grants from Mayo Clinic, Merck, Oxygen Therapeutics, Bristol Myers Squibb, AstraZeneca, University of Calgary, and Eli Lilly & Co; personal fees from CeleCor, Cytokinetics, and Novo Nordisk; and grants from Heart Flow outside the submitted work. Dr Velazquez reported receiving grants and personal fees from Novartis; personal fees from Philips; grants from Pfizer and the National Heart, Lung, and Blood Institute; and grants and personal fees from Amgen outside the submitted work. No other disclosures were reported.

Additional Contributions: Karen Chiswell, PhD, provided statistical oversight; Matthew Phelan, MS, provided statistical analyses during the revision period; and Michael MacKenzie, a senior analyst programmer, provided programming support (Duke Clinical Research Institute). Alicia Armour, RDCS (Duke Clinical Medical Center), provided stress echocardiography technical and protocol input. There was no financial compensation outside of salary.

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