Beyond borderline physiology: determinants of treatment choice and phenotypes of outcome in QFR grey-zone lesions.

BACKGROUND

The management of coronary lesions with quantitative flow ratio (QFR) values in the grey zone (0.75-0.85) remains a common clinical dilemma, with uncertain outcomes and unclear determinants guiding treatment selection in real-world practice. This study aimed to identify the clinical and angiographic factors influencing real-world treatment selection and compare clinical outcomes of percutaneous coronary intervention (PCI) versus medical therapy in the QFR grey zone.

METHODS

This retrospective study analyzed 297 coronary lesions with borderline QFR values (0.75-0.85). Patients were stratified by treatment (PCI vs. medication-only), with target vessel failure [TVF: cardiac death, target vessel myocardial infarction (MI), or ischemia-driven revascularization] as the primary endpoint. Baseline characteristics were compared using appropriate statistical tests. Time-to-event analysis used Kaplan-Meier curves and Cox proportional hazards models adjusted for clinical risk factors. To identify predictors of TVF within the grey zone, lesions were further stratified into QFR 0.75-0.80 and 0.81-0.85 subgroups, with interaction testing for variables significantly associated with TVF in the primary analysis.

RESULTS

Among 297 patients with coronary lesions in the QFR grey-zone (0.75-0.85), PCI (n=101) was performed for lesions with greater anatomic severity (smaller MLD, higher DS% and AS%, all P<0.001), while medical therapy (n=196) was favored for patients with higher HbA1c and proBNP (P=0.006 and P=0.02, respectively) and for lesions with length >20 mm (74.5% vs. 63.4%, P=0.046). At a mean follow-up of 526 days, the rate of TVF was not significantly different between treatment strategies (P=0.95). In multivariable analysis, only HbA1c (HR 2.04, 95% CI: 1.10-3.76, P=0.02) and left ventricular ejection fraction (LVEF) ≤45% independently predicted TVF (LVEF >45% HR 0.06, 95% CI: 0.01-0.55, P=0.01). A significant interaction was found between LVEF and QFR (Pinteraction=0.040), with impaired LVEF conferring a significantly higher risk of TVF under medical management, particularly in the lower QFR sub-range (≤0.80).

CONCLUSIONS

In patients with QFR grey-zone lesions, treatment selection balanced anatomic severity against clinical complexity. While overall outcomes were similar between strategies, impaired LVEF (≤45%) identified a high-risk phenotype for whom medical therapy was associated with worse outcomes, and poor glycemic control independently predicted TVF across the entire cohort. These findings suggest that a personalized approach-potentially including a lower threshold for revascularization in patients with reduced LVEF and intensified risk factor management in those with poor glycemic control-merits further investigation in prospective studies.