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

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.

To evaluate the clinical impact of adherence to FFR guidance in ACS.

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.

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).

In real-world ACS management, adherence to FFR guidance is associated with superior clinical outcomes compared with FFR-discordant decision-making.