Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial
Roxy SeniorHarmony R. ReynoldsJames K. MinDaniel S. BermanMichael H. PicardBernard ChaitmanLeslee J. ShawCourtney PageSajeev Chakanalil GovindanJosé López‐SendónJesús PeteiroGurpreet Singh WanderJarosław DróżdżJosé Antônio Marin‐NetoJoseph B. SelvanayagamJonathan NewmanChristophe ThuaireJohann ChristopherJames J. JangRaymond Y. KwongSripal BangaloreGregg W. StoneSean M. O’BrienWilliam E. BodenDavid J. MaronJudith S. Hochman
Key result
Clinical and stress testing parameters show modest accuracy for detecting left main CAD on CCTA.
- C-index 0.684
- P<0.001
- n=5,146
Why the study?
Detection of left main coronary artery disease has prognostic and therapeutic implications, but stress test markers of left main disease remain ill-defined.
Do clinical and stress testing parameters predict left main coronary artery disease on CCTA in patients with stable ischemic heart disease and moderate or severe ischemia?
Key Points
- To identify clinical and stress testing markers of left main coronary artery disease (LMD) detected on coronary computed tomography angiography (CCTA).
- Conducted a post hoc analysis of 5146 ISCHEMIA participants (mean age 63 years, 74% male) with moderate or severe ischemia on exercise tolerance testing (ETT), stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CCTA.
- Excluded patients with prior coronary artery bypass grafting, used core laboratory interpretations of stress tests, and developed stepped multivariate logistic regression models without and with stress testing parameters.
- A total of 414 participants (8%) had LMD, with older age (p<0.001), male sex (p<0.01), and absence of prior myocardial infarction (p<0.009) identified as clinical predictors.
- Modality-specific predictors included transient ischemic dilatation of the left ventricle on stress echocardiography (p=0.05), magnitude of ST-segment depression on ETT (p=0.004), and peak metabolic equivalents (METs) achieved on ETT (p=0.001).
- Multivariate models were weakly predictive of LMD, producing a C-index of 0.643 for clinical features alone and 0.684 after incorporating stress test variables.
Study Design
Type
Observational (n=5,146)
Blinding
Blinded core laboratory interpretation
Multicenter
Yes
Structured PICO
Do clinical and stress testing parameters predict left main coronary artery disease on CCTA in patients with stable ischemic heart disease and moderate or severe ischemia?
P
Population
5,146 adults (mean age 63, 26% female) with stable ischemic heart disease and moderate or severe ischemia on stress testing, evaluated for predictors of left main coronary artery disease.
E
Exposure
Clinical and stress testing parameters (exercise tolerance test, stress nuclear myocardial perfusion imaging, or stress echocardiography)
O
Outcome
Presence of left main coronary artery disease (LMD) defined as ≥50% diameter stenosis on coronary computed tomography angiography (CCTA)surrogate
Main Result
Effect estimate: C-index 0.684
p-value: p=<0.001
Clinical and stress testing parameters cannot reliably rule out left main coronary artery disease in patients with moderate or severe ischemia, highlighting the necessity of anatomic imaging like CCTA.
Limitations
- CCTA may overestimate stenosis severity
- Calcification may obscure stenosis assessment by CCTA
- Exercise hemodynamics were not routinely available for stress imaging tests
- 50-70% left main stenosis may not be flow limiting
- 24% of stress imaging tests and 23% of ETTs showed less than moderate/severe ischemia on core laboratory review
- Exercise hemodynamic data were not available in enough patients with stress imaging to permit inclusion
- CCTA may overestimate stenosis severity or be obscured by calcification
- Echocardiography was not used to identify flow in the LM coronary artery
Ask about this paper
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Thus, for most patients with moderate or severe ischemia, exclusion of LMD will require anatomical imaging with either CTA or invasive coronary angiography.”
Implication
Clinical parameters should not yet supplant anatomic imaging to exclude left main disease; leaves open whether refined models can improve prediction in stable ischemia.
Abstract
Background: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. Objectives: We sought to identify markers of LMD as detected on coronary computed tomography angiography (CCTA), using clinical and stress testing parameters. Methods: This was a post hoc analysis of ISCHEMIA, including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CCTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, we identified predictors of LMD, first without and then with stress testing parameters. Results: Among 5146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (p<0.001), male sex (p<0.01), absence of prior myocardial infarction (p<0.009), transient ischemic dilatation (TID) of the left ventricle on stress echocardiography (p=0.05), magnitude of ST-segment depression on ETT (p=0.004) and peak metabolic equivalents achieved (METs) on ETT (p=0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). Conclusions: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CCTA. For most patients with moderate or severe ischemia, anatomic imaging is needed to rule out LMD.
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Cite This Study
Senior et al. (2022) conducted an observational in Stable ischemic heart disease with moderate or severe ischemia (n=5,146). Clinical and stress testing parameters vs. Clinical parameters alone was evaluated on Prediction of left main coronary artery disease (LMD) ≥50% on CCTA (C-index 0.684, p=<0.001). Clinical and stress testing parameters were weakly predictive of left main coronary artery disease on CCTA, indicating anatomic imaging is needed to rule out LMD.