Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation

Background Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown. Methods Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18). Results At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 ± 0.06 to 0.82 ± 0.06, P = .009) but did not change in the rapamycin group (0.91 ± 0.05 to 0.89 ± 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 ± 1.7 to 3.2 ± 1.0, P = .76; and 27.5 ± 18.1 to 19.1 ± 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 ± 0.8 to 3.8 ± 1.4, P < .03; and 27.0 ± 11.5 to 17.6 ± 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation. Conclusion Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.