Influence of Local Myocardial Damage on Index of Microcirculatory Resistance and Fractional Flow Reserve in Target and Nontarget Vascular Territories in a Porcine Microvascular Injury Model

The aim of this study was to investigate the influence of microvascular damage in one vessel territory on invasively measured physiological parameters in the other vessel, using a porcine microvascular damage model. Although fractional flow reserve (FFR)-guided decision-making for the nonculprit stenosis in patients with acute myocardial infarction has been reported to be better than angiography-guided revascularization, there have been debates regarding the influence of microvascular dysfunction on measured FFR in nonculprit vessels. In Yorkshire swine, microvascular damage was induced with selective intracoronary injection of microspheres (100 μm × 105 each) into the left anterior descending artery (LAD). Coronary stenosis was created in both the LAD and the left circumflex artery (LCx) using balloon catheters. Coronary physiological changes were assessed with index of microcirculatory resistance (IMR) and FFR at baseline and at each subsequent injection of microsphere up to a fifth dose in both the LAD and LCx. Measurements were repeated 5 times at each stage, and a total of 424 measurements were made in 12 Yorkshire swine models. The median area stenosis in LAD and LCx was 48.1% (interquartile range: 40.8% to 50.4%) and 47.9% (interquartile range: 31.1% to 62.9%), respectively. At baseline, FFR in the LAD was lower than that in the LCx (0.89 ± 0.01 and 0.94 ± 0.01; p < 0.001). There was no difference in the IMR (18.4 ± 5.8 U and 17.9 ± 1.2 U; p = 0.847). With repeated injections of microspheres, IMR in LAD was significantly increased, up to 77.7 ± 15.7 U (p < 0.001). Given the same stenosis, FFR in the LAD was also significantly increased, up to 0.98 ± 0.01 along with IMR increase (p < 0.001). Conversely, IMR and FFR were not changed in the LCx throughout repeated injury to the LAD territory (p = 0.105 and p = 0.286 for IMR and FFR, respectively). The increase in LAD IMR was mainly driven by the increase in hyperemic mean transit time (p < 0.001). In Yorkshire swine models, local microvascular damage increased both FFR and IMR in a vessel supplying target myocardial territory. However, IMR and FFR were maintained in the other vessel. These physiological results in swine support the concept that FFR measurement might provide useful information for evaluating nonculprit lesions in clinical settings involving significant acute myocardial injury. [Display omitted]