Significance of Microvascular Function in Visual—Functional Mismatch Between Invasive Coronary Angiography and Fractional Flow Reserve

BACKGROUND Despite a moderate correlation between angiographical stenosis and physiological significance, the mechanism of discordance has not been fully elucidated, particularly regarding the significance of microvascular function. This study sought to clarify whether microvascular function affects visual-functional mismatch between quantitative coronary angiography (QCA) and fractional flow reserve (FFR). METHODS AND RESULTS We assessed QCA, FFR, coronary flow reserve, and the index of microcirculatory resistance in 849 non-left-main coronary lesions with visually estimated intermediate stenoses from 532 patients. Clinical and lesion-specific characteristics and physiological parameters associated with mismatch and reverse mismatch were studied. Coronary flow reserve and index of microcirculatory resistance showed a weak, but significant, correlation with FFR (R=0.306, P<0.001 and R=0.158, P<0.001, respectively). Four hundred twenty-two lesions were visually nonsignificant (diameter stenosis assessed by QCA [QCA-DS] ≤50%) and 427 lesions were visually significant (QCA-DS >50%). Among visually nonsignificant lesions, FFR ≤0.80 (reverse mismatch) was observed in 129 lesions (30.6%). Among visually significant lesions, FFR >0.80 (mismatch) were observed in 179 lesions (41.9%). The significant predictors of reverse mismatch were male sex, nonculprit lesions of acute coronary syndrome, left anterior descending artery location, smaller QCA reference diameter, greater QCA-DS, lower coronary flow reserve, and lower index of microcirculatory resistance. Mismatch was associated with right coronary artery location, greater QCA reference diameter, smaller QCA-DS, lesion length, higher coronary flow reserve, and higher index of microcirculatory resistance. CONCLUSIONS There was a high prevalence of visual-functional mismatches between QCA and FFR. The discrepancy was related to clinical characteristics, lesion-specific factors, and microvascular resistance that was undistinguishable by coronary angiography, thus suggesting the importance of physiological lesion assessment.