The RFR-FFR delta: a novel physiological signature of microvascular dysfunction and long-term mortality in patients undergoing LAD PCI

Background While fractional flow reserve (FFR) remains the gold standard for hemodynamic assessment of epicardial coronary stenosis, non-hyperemic pressure ratios (NHPRs), such as the resting full-cycle ratio (RFR), have emerged as simplified alternatives. However, recent evidence suggests that NHPR-guided revascularization may be associated with suboptimal clinical outcomes compared to FFR1.2. The physiological underpinnings of the discrepancy between these two metrics remain incompletely understood. Purpose We hypothesized that the numerical difference between RFR and FFR (the RFR-FFR delta) reflects a composite of systemic comorbidity burden and coronary microvascular impairment. This study aimed to elucidate the clinical significance of the RFR-FFR delta in patients with chronic coronary syndrome (CCS) and left anterior descending artery (LAD) stenosis, focusing on its association with microvascular function and long-term mortality. Methods In this retrospective single-center study, we evaluated 460 patients with CCS and significant LAD stenosis (FFR ≤ 0.80) who underwent FFR-guided elective PCI. All patients received pre-PCI comprehensive physiological assessment including RFR, FFR, coronary flow reserve (CFR), and microvascular resistance reserve (MRR). Patients were stratified into tertiles based on the RFR-FFR delta. The primary endpoint was all-cause mortality. Results Patients in the lowest RFR-FFR tertile exhibited a high-risk clinical phenotype, characterized by advanced age, female sex, increased NT-proBNP levels, and impaired renal function. Notably, a lower RFR-FFR delta was significantly associated with impaired microvascular indices, including lower CFR and MRR. Over a median follow-up of 5.2 years, the lowest tertile demonstrated the highest rate of all-cause mortality (Log-rank P = 0.030). Multivariable Cox proportional hazards analysis identified an RFR-FFR delta < 0.060 (HR: 1.86; 95% CI: 1.01–3.45; P = 0.048) and log NT-proBNP as independent predictors of death. Conclusions The RFR-FFR delta serves as a potent integrator of systemic comorbidities and coronary microvascular dysfunction in patients undergoing FFR-guided PCI. A lower RFR-FFR gap identifies a high-risk patient subset with unfavorable long-term survival. This novel preprocedural metric facilitates refined risk stratification and supports a personalized approach to the management of complex coronary artery disease.