Journal Article Randomized Controlled Trial Multicenter Study Ppublish
PubMed: 42384892 DOI: 10.1161/CIRCOUTCOMES.125.012920
Variability in Cardiac Stress Test Interpretation: Agreement Between Enrollment Sites and Core Laboratories in the Global ISCHEMIA Trial.
Circ Popul Health Outcomes 19(8):e012920
Authors: Evan L O'Keefe, Brett W Sperry, Philip G Jones, James H O'Keefe, Lawrence M Phillips, Harmony R Reynolds, Leslee J Shaw, Daniel S Berman, Michael H Picard, Raymond Y Kwong, Bernard R Chaitman, Timothy M Bateman, Sripal Bangalore, David J Maron, Judith S Hochman, John A Spertus
Affiliations
- Saint Luke's Mid America Heart Institute, Kansas City, MO (E.O.K. B.W.S. P.G.J. J.H.O.K. T.M.B. J.A.S.).
- University of Missouri-Kansas City's Healthcare Institute for Innovations in Quality, MO (E.O.K. P.G.J. J.A.S.).
- Cardiovascular Clinical Research Center, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine (L.M.P. H.R.R. S.B. J.S.H.).
- Icahn School of Medicine at Mount Sinai, NY (L.J.S.).
- Cedars-Sinai Medical Center, Los Angeles, CA (D.S.B.).
- Department of Medicine, Cardiovascular Division, Massachusetts General Hospital, Harvard Medical School, Boston (M.H.P.).
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.Y.K.).
- St. Louis University School of Medicine Center for Comprehensive Cardiovascular Care, MO (B.R.C.).
- Department of Medicine, Stanford University School of Medicine, CA (D.J.M.).
Abstract
BACKGROUND
Cardiac stress testing is a cornerstone of risk stratification and management in patients with chronic coronary disease, yet the consistency and accuracy of its interpretation remain poorly defined. This analysis evaluated variation in the interpretation of myocardial ischemia between enrollment sites and core laboratories in the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches).
METHODS
ISCHEMIA was a global (37 countries, 2012-2018) randomized trial of an initial invasive versus conservative strategy in patients with chronic coronary disease and moderate or severe ischemia. This analysis included participants with site-interpreted qualifying stress tests-nuclear, echocardiography (echo), cardiac magnetic resonance, or exercise tolerance test-and independent core laboratory adjudication. Core laboratories, serving as the reference standard, reinterpreted tests blinded to site results. A trinary outcome variable (site underestimation, concordance, or overestimation) was defined by comparing site-determined ischemia levels to standardized core lab assessments. Adjusted mixed-effects logistic regression models with random site intercepts assessed variability.
RESULTS
Among 6971 participants (mean age, 62.8 years; 73% men), site interpretations showed 0% no/mild (by design), 43% moderate, and 57% severe ischemia. Core labs reclassified these as 8% none, 11% mild, 30% moderate, and 51% severe ischemia. For the imaging modalities, median site-core lab agreement rates were ≈55%; nearly 25% of site-classified moderate/severe cases were downgraded to no or mild ischemia by core labs. Adjusted median odds ratios for site overestimation were 2.36 (95% CI, 2.02-2.82; nuclear), 1.98 (95% CI, 1.62-2.60; echo), 1.89 (95% CI, 1.0-5.41; cardiac magnetic resonance), and 2.15 (95% CI, 1.76-2.79; exercise tolerance test). Adjusted median odds ratios for underestimation ranged from 1.25 to 1.77.
CONCLUSIONS
In ISCHEMIA, enrollment sites frequently overestimated or underestimated the severity of myocardial ischemia compared with core laboratory assessments, highlighting the need for strategies to improve the consistency and accuracy of stress testing interpretation in patients with chronic coronary disease.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
MeSH
Exercise, Myocardial Ischemia, Research Design, Exercise Tolerance, Laboratories, Stress, Physiological, Odds Ratio, Echocardiography, Coronary Disease, Ischemia