Clinical Impact of Adherence to Fractional Flow Reserve Guidance in Acute Coronary Syndrome

BACKGROUND: Fractional flow reserve (FFR) is established to guide revascularization in stable coronary disease and non-culprit lesions in acute coronary syndromes (ACS). However, real-world adherence to FFR guidance across the spectrum of ACS presentations, including ambiguous culprit scenarios, remains incompletely characterized. AIMS: To evaluate the clinical impact of adherence to FFR guidance in ACS. METHODS: From a multicenter prospective FFR registry, we analyzed 501 ACS patients who underwent FFR measurement: 222 with clear culprit lesions and 279 with ambiguous culprit lesions. Patients were classified as FFR-concordant (all FFR ≤ 0.80 treated; all FFR > 0.80 deferred) or FFR-discordant (≥ 1 FFR-hemodynamic mismatch). The patient-oriented composite endpoint (POCE) comprised all-cause death, myocardial infarction, or any revascularization; the patient-oriented FFR-related composite endpoint (POFRC) comprised cardiac death or myocardial infarction or revascularization involving an FFR-assessed vessel at 2 years. RESULTS: Among 501 patients, 431 (86%) received FFR-concordant management and 70 (14%) FFR-discordant management. FFR discordance clustered in the gray zone (0.75-0.85), with 3.5-fold higher prevalence compared with other FFR ranges. Over 2 years, FFR-discordant management was associated with significantly higher POCE (Kaplan-Meier incidence 20.0% vs. 10.4%; propensity-weighted hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.27-4.29, p = 0.009). The POFRC confirmed and strengthened this association (19.0% vs. 8.8%; propensity-weighted HR 2.59, 95% CI 1.37-4.91, p = 0.004). The adverse impact of FFR discordance was consistent across clear culprit and ambiguous culprit subgroups (p for interaction = 0.52) and across types of ACS (p for interaction = 0.91). CONCLUSIONS: In real-world ACS management, adherence to FFR guidance is associated with superior clinical outcomes compared with FFR-discordant decision-making.