Establishing Thrombolysis in Myocardial Infarction Frame Count as a Clinical Measure of Coronary Microvascular Disease in Women

Background Despite growing awareness of the crucial role of the coronary vasculature in cardiovascular health and disease, diagnosing coronary microvascular disease (CMVD) remains challenging because it often requires advanced cardiac imaging that are available at only a few centers. For example, perfusion positron emission tomography (PET) allows for the quantification of the myocardial blood flow (MBF) and, thus, the calculation of the MBF reserve (MBFR), which is the ratio of MBF under rest conditions and MBF under hyperemic or stress conditions. In the absence of obstructive coronary artery disease, MBFR is a measure of CMVD. However, the availability of perfusion PET is limited. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based measure of coronary flow that has been proposed, but not well established, as a measure of CMVD. We aim to demonstrate a relationship between TFC and MBFR and to establish cut-off measures from clinical coronary angiograms for the diagnosis of CMVD. Methods We identified a cohort of 123 patients (age 58 +/− 12.1, 63% female, 41% Caucasian) who had no obstructive coronary artery disease and had undergone perfusion PET stress testing and clinical coronary angiography for clinical indications. We compared TFC for each coronary territory with regional perfusion PET parameters using linear regression modeling. We then used two mathematical models of the coronary circulation to understand the relationship between these parameters. We performed ROC analysis to determine the ability of TFC to diagnose CMVD, defined as global MBFR < 2. Results There is a very tight sex-dependent correlation between TFC and MBFR, but no association between resting coronary flow and TFC and only a weak association between stress coronary flow and TFC. Mathematical modeling of the coronary circulation highlights an uncoupling between TFC and flow in larger vessels where TFC is measured, providing a likely explanation for the surprising empiric result. ROC analysis shows TFC as an excellent measure of CMVD in women (AUC 0.84-0.89) and establishes TFC cutoffs. Conclusions TFC from clinical coronary angiograms reflects coronary microvascular function in a sex-dependent manner and performs well in identifying women with CMVD. Clinical Perspective What is new? Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is highly correlated with myocardial blood flow reserve (MBFR), which reflects coronary vasodilatory potential, in patients without obstructive coronary artery disease. Computational modeling establishes how the relationship between TFC and MBFR can exist. TFC performs much better in women than in men for the diagnosis of coronary microvascular disease (CMVD) and thresholds for the diagnosis of CMVD with TFC are identified. What are the clinical implications? TFC from clinical coronary angiograms can be used to assess CMVD in women.