Head‐to‐Head Comparison of Quantitative Flow Ratio, Intravascular Ultrasound, and Coronary Angiography in Left Main Coronary Artery Disease

Background Intermediate left main coronary artery (LMCA) disease poses a significant diagnostic challenge. Intravascular ultrasound (IVUS) is the guideline‐recommended reference standard for anatomical assessment, whereas quantitative flow ratio (QFR) provides a wire‐free physiological estimate. Conventional coronary angiography (CCA) remains the most widely available assessment modality. However, a systematic three‐way comparison of these modalities in LMCA disease is lacking. Aims To compare the diagnostic performance, agreement, and correlations of CCA and QFR with IVUS for the assessment of intermediate LMCA disease. Methods This prospective single‐center study enrolled 135 patients with LMCA lesions who underwent CCA, IVUS, and offline QFR (QAngio XA 3D) between January 2024 and June 2025. IVUS‐derived minimum lumen area (MLA) < 6 mm 2 was defined as anatomically significant disease and served as the reference standard. QFR < 0.80 defined functional significance, while CCA diameter stenosis (DS) ≥ 50% defined angiographic significance. Diagnostic performance, inter‐modality agreement, correlation, and Bland–Altman agreement were assessed. Results The mean age was 63.4 ± 9.7 years, and 88.1% of patients were male. IVUS identified significant disease in 92 patients (68.1%), compared with 68 (50.4%) by CCA and 50 (37.0%) by QFR. Against the IVUS reference standard, CCA demonstrated 67.4% sensitivity and 86.0% specificity (κ = 0.465; AUC = 0.824; optimal threshold DS ≥ 47%), whereas QFR demonstrated 54.3% sensitivity and 100% specificity (κ = 0.426; AUC = 0.848; Youden‐optimal cutoff QFR ≤ 0.49). CCA correlated moderately with IVUS‐derived MLA (r = −0.384; p < 0.001) and QFR (r = −0.512; p < 0.001). Both CCA and QFR systematically underestimated vessel dimensions relative to IVUS (Bland–Altman bias: CCA − 2.50 mm 2 ; QFR − 2.21 mm 2 ). On multivariable analysis, CCA DS ≥ 50% (OR 2.87; p = 0.011), decreasing QFR value per 0.1‐unit (OR 0.61; p = 0.019), and distal bifurcation location (OR 2.38; p = 0.045) independently predicted IVUS‐defined significant disease. Conclusion QFR demonstrated perfect specificity and may serve as a rule‐in tool, whereas CCA provided greater sensitivity for initial triage. Neither modality can replace IVUS for anatomical characterization and procedural planning. A multimodality approach may therefore be appropriate for the assessment of intermediate LMCA stenosis.