Anatomical Imaging Helps to Rule out LMD in Severe or Moderate Ischemia: ISCHEMIA

Predicting or ruling out LMD with accuracy has long been known to be the Achilles' heel of noninvasive stress imaging. Existing data is limited to smaller studies with significant heterogeneity. Therefore, Dr Roxy Senior and his team conducted a study to identify markers of LMD as detected on coronary CTA, using clinical and stress testing parameters.

The researchers conducted a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on non-imaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. They evaluated stress tests by core laboratories. They used a stepped multivariate model to identified predictors of LMD, first without and then with stress testing parameters. They assessed the model's ability to distinguish between patients with relatively high versus the low likelihood of LMD >50% by calculating the C-index and by plotting the distribution of predicted probabilities of LMD >50% within each modality.

Key findings of the study:

• Among 5,146 patients, the researchers observed that 414 (8%) had LMD.
• They found that the predictors of LMD were older age, male sex, absence of prior myocardial infarction, transient ischemic dilation of the left ventricle on stress echocardiography, the magnitude of ST-segment depression on ETT and peak metabolic equivalents achieved on ETT.
• They noted that the models were weakly predictive of LMD (C-index 0.643 and 0.684).

The authors concluded, "In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD."

In an accompanying editorial, Dr Waleed T. Kayani and his team wrote, "Senior et al, help generate more questions and will help lay the foundation for future investigations. As for the clinical question, based on this and all prior evidence, the answer remains that we need to apply all tools at hand. A careful assessment of a patient's risk factor profile and noninvasive imaging results can help guide. But, to accurately rule out LMD, for now, anatomical imaging remains the modality of choice".

In a summary report, Dr Debabrata Mukherjee wrote, "This post hoc study suggests that stress testing offered only modest incremental value over clinical parameters for prediction of LMD in those with moderate or severe ischemia. Furthermore, transient ischemic dilation by stress echocardiography, and the magnitude of ST-segment depression, and low achieved workload by ETT were associated with LMD independent of clinical factors but, the discriminatory capacity of the model was modest. There was high concordance of CTA and invasive angiography for LMD in the ISCHEMIA trial and for most patients, exclusion of LMD will require anatomical imaging, with either CTA or invasive coronary angiography."

For further information:

DOI: https://www.jacc.org/doi/10.1016/j.jacc.2021.11.052