December 31, 2013 — A study published in the Journal of the American Heart Association revealed findings that may impact diagnostic strategies and clinical decision-making for patients with suspected coronary artery disease (CAD).
The study, “Clinical Implications of Referral Bias in the Diagnostic Performance of Exercise Testing for Coronary Artery Disease,” examined the issue of referral bias in assessments of diagnostic performance for exercise testing with echocardiography (echo) or myocardial perfusion imaging (MPI).
Referral bias occurs when patients with an abnormal stress test result are referred to cardiac catheterization at a higher rate than patients with normal stress test results. While clinically appropriate, failing to adjust for this difference in referral rates when measuring test performance can significantly distort the observed diagnostic characteristics of exercise testing.
The study authors conducted a meta-analysis of 21 studies examining CAD referral patterns in 49,006 patients. After systematically reviewing cardiac catheterization referral rates and aggregating them to adjust pooled estimates of exercise test performance, the authors found that adjusting for referral bias significantly reduced test sensitivity and increased test specificity.
“We found that the sensitivity of exercise testing is much lower than previously reported. Wider recognition of this among clinicians — particularly primary care physicians and hospitalists — may influence how healthcare professionals use exercise echo and MPI to rule-in versus rule-out disease,” said Joseph Ladapo, M.D., Ph.D., assistant professor, departments of population health and medicine, NYU Langone Medical Center, and lead author.
The study found exercise echocardiography and myocardial perfusion imaging are considerably less sensitive and more specific for CAD after adjustment for referral. Given these findings, researchers said future work should assess the comparative ability of these and other tests to rule?in versus rule?out coronary artery disease.
A K23 Career Development Award from the National Heart, Lung, and Blood Institute (NHLBI) supported Ladapo’s work. CardioDx also helped fund the study.
For more information: jaha.ahajournals.org
November 12, 2025 
