Variability in Cardiac Stress Test Interpretation: Agreement Between Enrollment Sites and Core Laboratories in the Global ISCHEMIA Trial
Authors' conclusion
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.
Study context
- Population
- Participants in the ISCHEMIA trial with chronic coronary disease and moderate or severe ischemia, with site-interpreted qualifying stress tests (nuclear, echo, cardiac magnetic resonance, or exercise tolerance test) and independent core laboratory adjudicationmean age, 62.8 years, 73% men
- Participants
- 6,971 participants
- Comparison
- Site-determined ischemia levels compared to standardized core lab assessments
Methodological detailsglobal (37 countries, 2012-2018), core laboratories, serving as the reference standard, reinterpreted tests blinded to site results, adjusted mixed-effects logistic regression models with random site intercepts
- Global (37 countries, 2012-2018)
- Core laboratories, serving as the reference standard, reinterpreted tests blinded to site results
- Adjusted mixed-effects logistic regression models with random site intercepts
Primary result
As reported in the abstract
Ischemia severity classification
Moderate
Severe
| Outcome | Enrollment sites | Core laboratories |
|---|---|---|
| No/mild (by design) | 0% | — not stated in the abstract |
| None | — not stated in the abstract | 8% |
| Mild | — not stated in the abstract | 11% |
— not stated in the abstract
Further findings
Site overestimation (adjusted median odds ratio)
| Adjusted median odds ratio (95% CI) | ||
|---|---|---|
| Enrollment sitesNuclear | 2.36 (2.02–2.82) | |
| Enrollment sitesEcho | 1.98 (1.62–2.60) | |
| Enrollment sitesCardiac magnetic resonance | 1.89 (1.0–5.41) | |
| Enrollment sitesExercise tolerance test | 2.15 (1.76–2.79) | |
| 0.20.5125Adjusted median odds ratio (log scale) |
Site-core lab agreement, imaging modalities
- Median site-core lab agreement rates
- ≈55%
- Site-classified moderate/severe cases downgraded to no or mild ischemia by core labs
- nearly 25%
Site underestimation (adjusted median odds ratio)
- Adjusted median odds ratios for underestimation ranged from
- 1.25 to 1.77
Original publication
Variability in Cardiac Stress Test Interpretation: Agreement Between Enrollment Sites and Core Laboratories in the Global ISCHEMIA Trial. Circ Popul Health Outcomes. Published 1 July 2026. doi:10.
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