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Incremental Prognostic Power of Coronary Flow Reserve and Artificial Intelligence-Enabled ECG-Derived Filling
Parvin Kalhor1, Matteo Manzato1, Elias Hellou1
1Department of Cardiovascular Medicine Mayo Clinic Rochester MN.
Insights
Coronary microvascular dysfunction and elevated filling pressure are linked to adverse events in angina patients. Combining these markers improves risk prediction for major cardiovascular events.
Area of Science:
- Cardiology
- Vascular Biology
- Biomedical Engineering
Background:
- Coronary flow reserve assesses microvascular function, while filling pressure indicates myocardial hemodynamic burden.
- In angina with nonobstructive coronary arteries (ANOCA), either abnormality can cause supply-demand mismatch, but their combined prognostic impact is unknown.
Purpose of the Study:
- To investigate the combined prognostic significance of coronary microvascular dysfunction (CMD) and elevated filling pressure, assessed by an AI-enabled ECG marker (AIEFP), in patients with ANOCA.
Main Methods:
- Retrospective study of 1957 ANOCA patients undergoing invasive coronary reactivity testing.
- CMD defined as coronary flow reserve <2.5; AIEFP identified elevated filling pressure.
- Cox regression and propensity score overlap weighting analyzed associations with major adverse cardiovascular events (MACE).
Main Results:
- CMD identified in 26.4%, AIEFP in 6.6%; 10.4% experienced MACE over 8 years.
- Both CMD (HR=1.42) and AIEFP (HR=2.28) were independently associated with MACE.
- AIEFP improved model fitness and discrimination; risk increased gradedly across four groups (CMD-/AIEFP-, CMD+/AIEFP-, CMD-/AIEFP+, CMD+/AIEFP+).
Conclusions:
- CMD and AIEFP offer complementary prognostic information in ANOCA.
- AIEFP remains significantly associated with outcomes after adjustment.
- A dual-axis framework integrating hemodynamic stress and microvascular function enhances risk stratification for distinct ANOCA phenotypes.
Background:
Coronary flow reserve reflects microvascular function, whereas filling pressure indicates myocardial hemodynamic burden. In angina with nonobstructive coronary arteries, abnormalities in either could contribute to a supply-demand mismatch; however, their combined prognostic significance remains unclear.
Methods:
Patients with angina with nonobstructive coronary arteries who underwent invasive coronary reactivity tests were studied retrospectively. Coronary microvascular dysfunction (CMD) was coronary flow reserve <2.5. An artificial intelligence-enabled ECG marker of elevated filling pressure (AIEFP) was applied as a scalable prognostic marker of myocardial hemodynamic stress. Associations with major adverse cardiovascular events were evaluated using Cox regression and propensity score overlap weighting.
Results:
Among 1957 patients with angina with nonobstructive coronary arteries (median age, 51.8 years; 67.2% women), CMD+ was identified in 26.4% and AIEFP+ in 6.6%. Over 8 years, 204 patients (10.4%) experienced major adverse cardiovascular events. In nested models, both CMD (hazard ratio [HR]=1.42 [95% CI=1.13-1.78]; P=0.002) and AIEFP (HR=2.28 [95% CI=1.67-3.11]; P<0.001) remained associated with major adverse cardiovascular events after adjustment. Adding AIEFP to the base model improved model fitness (Δχ2=23.65, P<0.001; ΔAkaike Information Criterion=-21.7) and modestly improved discrimination (ΔHarrell concordance index=0.02, P=0.02). In a 4-group model, adjusted risks increased in a graded manner. Overlap-weighted analysis after covariate balance demonstrated distinct temporal risk trajectories: CMD+/AIEFP+ had the highest 1-year risk (12.7%), and AIEFP+ had the highest cumulative 8-year risk (57% in CMD- and 51.8% in CMD+).
Conclusions:
CMD and AIEFP provide complementary prognostic information, with AIEFP remaining significantly associated with outcomes after multivariable adjustment. A dual-axis framework integrating myocardial hemodynamic stress (AIEFP) and microvascular function (coronary flow reserve) may enhance risk stratification and enable identification of clinically distinct angina with nonobstructive coronary arteries phenotypes with divergent trajectories.
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