INTegrated Assessment of intERmediate Coronary Stenoses by Fractional Flow rEserve and Near-infraREd Spectroscopy: The INTERFERE Study

<b>Background/Objectives:</b> Fractional flow reserve (FFR) is the most widely used intracoronary physiological index to guide coronary revascularization but does not allow for a precise assessment of plaque morphology. The combined use of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) can detect angiographically non-obstructive lesions with high lipid content and large plaque burden, which are associated with an increased risk of future adverse cardiac events. The aim of this study is to perform an integrated assessment of angiographically intermediate coronary lesions using both FFR and IVUS-NIRS, in order to evaluate the distribution of plaque vulnerability features-assessed by IVUS-NIRS-in functionally significant and non-significant lesions. <b>Methods:</b> This was a double-center, observational, prospective study including patients undergoing coronary angiography for both stable coronary artery disease and acute coronary syndrome, provided they had at least one angiographically borderline (40-70%) stenosis. The index lesion was evaluated with both FFR and IVUS-NIRS; revascularization decisions were guided by the FFR result. The following features were considered markers of plaque vulnerability: minimal lumen area (MLA) < 4.0 mm², plaque burden (PB) > 70%, and maximum lipid core burden index within any 4 mm segment (maxLCBI4mm) > 325. High-risk plaques were defined by the simultaneous presence of all three criteria. <b>Results:</b> A total of 57 patients were enrolled (mean age: 66 years; 18% women), and 57 lesions were assessed using both FFR and IVUS-NIRS. Acute coronary syndrome was the admission diagnosis in 72% of patients. Twenty-five lesions with FFR < 0.80 were classified as Group A, while the remaining thirty-two lesions with FFR > 0.80 were labeled as Group B. The percentage of lesions with MLA < 4 mm² and plaque burden > 70% was 72% and 67%, respectively, with no significant differences between Groups A and B. On NIRS analysis, 23% of lesions had a maxLCBI4mm > 325, again with no significant difference between the two groups. High-risk plaques-defined by the concurrent presence of MLA < 4 mm², plaque burden > 70%, and maxLCBI4mm > 325-were identified in 18% of patients. The prevalence of high-risk plaques did not differ significantly between Groups A and B (12% vs. 22%, <i>p</i> = 0.33). <b>Conclusions:</b> Plaque vulnerability criteria are equally distributed between functionally significant and non-significant coronary lesions, and the prevalence of high-risk plaques (defined by the simultaneous presence of MLA < 4 mm², PB > 70%, and maxLCBI4mm > 325) does not differ significantly between the two groups. Notably, 22% of FFR-negative lesions managed conservatively are characterized by the presence of high-risk plaques. Further studies are needed to determine whether these lesions warrant interventional treatment or a more intensive pharmacological approach. (ClinicalTrials.gov # NCT02985112).