Abhiram, P

Abstract Background Coronary flow augmentation occurs through the simultaneous interaction and regulation of both endothelium-dependent and endothelium-independent mechanisms. A decrease in coronary flow reserve (CFR) secondary to either mechanism is associated with poor prognosis. However, at the individual level, the integrated impact of these two mechanisms has not been thoroughly investigated. Purpose This study investigated the prognostic implications of an integrated metric, CFRsum, combining endothelium-dependent and -independent CFR. Methods A total of 1441 patients with angina with non-obstructive coronary artery (ANOCA) undergoing coronary reactivity testing were studied. Endothelium-independent CFR was measured during adenosine-induced hyperemia, and endothelium-dependent CFR during intracoronary acetylcholine infusion. CFRsum was calculated by summing these components. Cardiovascular event was defined as composite of cardiovascular death, myocardial infarction, heart failure, and cerebral infarction. Results Our patients had a median age of 51.7 years, 69.0% of whom were female, and their CFRsum was 4.57 [3.88, 5.37]. Patients were divided into three tertile-based groups, and Cox proportional hazards analysis demonstrated that all CFR classes were independent predictors of prognosis, with CFRsum providing the best model fit (Likelihood ratio: 54.62, degrees of freedom: 7, P < 0.001). The Kaplan-Meier curve (Figure) demonstrated a stepwise deterioration in prognosis across CFRsum tertile groups, with lower CFRsum being associated with progressively worse outcomes (p < 0.001). Stratification by follow-up duration (3 years) revealed that patients with middle-range CFRsum exhibited comparable outcomes to those with the highest CFRsum during the early phase (<3y) but significantly worse outcomes in the late phase (≥3y) (P = 0.459 and P < 0.001, respectively). Conclusion CFRsum showed superior prognostic value over traditional CFR metrics in patients with ANOCA, identifying a compensated group with time-varying outcomes. This novel metric improves the assessment of microvascular function and supports better clinical management.