FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study

Study Questions:

What is the optimal minimum lumen area (MLA) by intravascular ultrasound (IVUS) that correlates with fractional flow reserve (FFR)?


The FIRST is a multicenter, prospective, international registry of patients with intermediate coronary lesions, defined as 40-80% stenosis by angiography. In total, 350 patients (367 lesions) were enrolled at 10 US and European sites. Patients were followed through hospital discharge. Logistic regression and receiver-operating characteristic curve analyses were performed to establish the value of IVUS indexes most predictive of FFR <0.8.


Overall, an MLA <3.07 mm2 (64.0% sensitivity, 64.9% specificity, area under curve [AUC] = 0.65) was the best threshold value for identifying FFR <0.8. The accuracy improved when reference vessel–specific analyses were performed. An MLA <2.4 mm2 (AUC = 0.66) was best for reference vessel diameters <3.0 mm, an MLA <2.7 mm2 (AUC = 0.71) for reference vessel diameters of 3.0-3.5 mm, and an MLA <3.6 mm2 (AUC = 0.68) for reference vessel diameters >3.5 mm. FFR correlated with plaque burden (r = -0.220, p < 0.001), but not with other plaque morphology.


The authors concluded that anatomic measurements by IVUS show a moderate correlation with the FFR values.


This study suggests that the correlation between MLA by IVUS and FFR is modest and varied depending on the vessel size, with increasing correlations in larger vessel diameters. Based on these data, different MLA cutoffs should be used for different vessel sizes. Furthermore, plaque composition assessed by virtual histology (VH)-IVUS does not appear to correlate with FFR for the detection of ischemia in intermediate lesions. Overall, it appears that the utility of IVUS MLA as an alternative to FFR to guide intervention in intermediate lesions may be limited in accuracy, and needs to be tested and confirmed in additional clinical studies.

Keywords: Registries, Plaque, Atherosclerotic, Area Under Curve, Coronary Stenosis, Coronary Angiography, Cardiology, Sensitivity and Specificity, Coronary Circulation, Histological Techniques, ROC Curve, Angioplasty, Logistic Models

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