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Variability in Cardiac Stress Test Interpretation: Agreement Between Enrollment Sites and Core Laboratories in the
Evan O'Keefe1,2, Brett W Sperry1, Philip G Jones1,2
1Saint 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.).
Insights
Site interpretations of cardiac stress tests in the ISCHEMIA trial frequently overestimated or underestimated myocardial ischemia severity. This highlights the need for improved consistency and accuracy in interpreting stress tests for chronic coronary disease management.
Area of Science:
- Cardiology
- Medical Imaging
- Clinical Trials
Background:
- Cardiac stress testing is crucial for managing chronic coronary disease.
- Interpretation consistency and accuracy of stress tests are not well-defined.
- The ISCHEMIA trial evaluated variations in ischemia interpretation between sites and core labs.
Purpose of the Study:
- To evaluate variability in myocardial ischemia interpretation.
- Compare site interpretations with core laboratory assessments in the ISCHEMIA trial.
- Identify overestimation and underestimation of ischemia severity by enrollment sites.
Main Methods:
- Analysis of data from the ISCHEMIA trial (37 countries, 2012-2018).
- Included participants with site-interpreted stress tests (nuclear, echo, CMR, stress ECG) and core lab adjudication.
- Used a trinary outcome variable (underestimation, concordance, overestimation) comparing site vs. core lab results.
Main Results:
- Core labs reclassified site interpretations, revealing significant discrepancies.
- Nearly 25% of moderate/severe ischemia cases by sites were downgraded to no/mild by core labs.
- Enrollment sites frequently overestimated ischemia severity (ORs 1.89-2.36) and sometimes underestimated it (ORs 1.25-1.77).
Conclusions:
- Enrollment sites in the ISCHEMIA trial showed frequent overestimation and underestimation of myocardial ischemia.
- Significant variability exists in interpreting cardiac stress tests.
- Strategies are needed to enhance the consistency and accuracy of stress test interpretation for chronic coronary disease patients.
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.
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