Angio-IMR alone is not enough: A survival tree for risk stratification in CCS

The prognostic value of the angiography-derived index of microcirculatory resistance (Angio-IMR) in chronic coronary syndrome (CCS) remains unclear, particularly regarding its interaction with other clinical variables.

We enrolled 1415 CCS patients who underwent coronary angiography and were followed for 2 years for major adverse cardiovascular events (MACE). A survival tree was applied within the Angio-IMR-high subgroup to identify prognostic factors, and four risk groups were derived. Multivariable Cox regression and bootstrap resampling were used for model validation. The net reclassification improvement (NRI) was calculated to assess the incremental prognostic value beyond Angio-IMR alone.

The survival tree identified NT-proBNP, age, and coronary stenosis severity as splitting variables, forming a stepwise risk gradient: the very-low-risk group (n = 223, 0% MACE), the low-risk group (n = 704, 4.0%), the intermediate-risk group (n = 389, reference, 7.5%), and the high-risk group (n = 99, 19.2%). After multivariable adjustment, the high-risk group remained independently associated with a significantly higher risk of MACE (HR 2.41, 95%CI 1.30-4.46, P = 0.005), whereas the low-risk group had a lower risk (HR 0.54, 95%CI 0.32-0.91, P = 0.020). The tree-derived groups significantly improved risk reclassification compared with Angio-IMR alone (NRI 0.309, 95%CI 0.183-0.549, P = 0.001). Notably, systemic inflammatory markers (SIRI, NLR) increased stepwise across the groups (both P < 0.001), paralleling the risk gradient. An online risk calculator was developed based on these findings (https://heartlab.shinyapps.io/calculator/).

Angio-IMR alone does not adequately stratify risk in CCS. Integrating it with NT-proBNP, age, and coronary stenosis severity via a survival tree significantly improves 2-year MACE prediction, enabling precision targeting of preventive therapies.