Multimodality assessment of the coronary microvasculature with TIMI frame count versus perfusion PET highlights coronary changes characteristic of coronary microvascular disease.

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The diagnosis of coronary microvascular disease (CMVD) remains challenging. Perfusion PET-derived myocardial blood flow (MBF) reserve (MBFR) can quantify CMVD but is not widely available. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based method that has been proposed as a measure of CMVD. Here, we compare TFC and PET-derived MBF measurements to establish the role of TFC in assessing for CMVD. We use coronary modeling to elucidate the relationship between MBFR and TFC and propose TFC thresholds for identifying CMVD. In a cohort of 123 individuals (age 58 ± 12.1, 63% women, 41% Caucasian) without obstructive coronary artery disease who had undergone perfusion PET and coronary angiography for clinical indications, we compared TFC and perfusion PET parameters using Pearson correlation (PCC) and linear regression modeling. We used mathematical modeling of the coronary circulation to understand the relationship between these parameters and performed Receiver Operating Curve (ROC) analysis. We found a significant negative correlation between TFC and MBFR. Sex, race and ethnicity, and nitroglycerin administration impact this relationship. Coronary modeling showed an uncoupling between TFC and flow in epicardial vessels. In ROC analysis, TFC performed well in women (AUC 0.84-0.89) and a moderately in men (AUC 0.68-0.78). We established an inverse relationship between TFC and PET-derived MBFR, which is affected by patient selection and procedural factors. TFC represents a measure of the volume of the epicardial coronary compartment, which is increased in patients with CMVD, and performs well in identifying women with CMVD.