ABSTRACT

OBJECTIVES - To assess the relationship between anatomical form and physiological function in atherosclerotic coronary arteries.

BACKGROUND - Although adverse cardiovascular events are predicted by plaque morphology or invasively-derived hemodynamic indices, the link between these important prognostic measures remains unexplored.

METHODS - Patients with stable angina underwent fractional flow reserve (FFR), coronary flow reserve (CFR), pressure-derived collateral flow index (CFIp), trans-myocardial biomarker sampling and radiofrequency intravascular ultrasound (IVUS) imaging prior to intervention. Physiological ischemia was defined as either FFR≤0.8 or CFR<2.0.

RESULTS - Mean FFR was 0.70±0.15 and CFR was 2.1±1.3, with 68/92 lesions having FFR≤0.8 and 61/92 having CFR<2.0. On IVUS, FFR≤0.8 lesions had reduced minimal luminal area (MLA, p=0.03), increased plaqueburden (PB, p=0.04) and volume (p=0.01). There was no relationship between FFR and IVUS-defined plaque composition. FFR≤0.8 was observed in 75.3%, 72.4% and 70.4% of lesions with MLA≤4mm2, PB≥70% and thin-cap fibroatheroma, respectively. Multivariate regression demonstrated FFR≤0.8 was independently predicted by MLA (odds ratio (OR) 0.53, 95% CI 0.29-0.97, p=0.04) and PB (OR 1.10, 95% CI 1.01-1.21, p=0.03). There were no identifiable relationships between plaque structure and CFR or CFIp. CFR<2.0 was associated with whole vessel necrotic core increases (p=0.047), fibrofatty tissue reduction (p=0.004) and elevated baseline transmyocardial high-sensitivity C-reactive protein (hsCRP) gradients (p=0.02).

CONCLUSIONS - Measures of plaque structure including PB and MLA are independently associated with FFR, but not with CFR or CFIp. Instead, vessels with low CFR have increased lipid accumulation and a higher transmyocardial hsCRP gradient. These results may explain similarities in clinical outcomes between physiologically and anatomically orientated trials.