Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation

Abstract

Background: PET myocardial flow reserve (MFR) is a noninvasive method to detect cardiac allograft vasculopathy in heart transplant (HT) recipients. There is limited data on longitudinal change and predictors of MFR following HT. Methods: We conducted a retrospective analysis of HT recipients undergoing PET MPI at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors, and prognostic value of MFR after HT. Results: 183 HT recipients underwent 658 PET studies. Average MFR was 2.34 ± 0.70. MFR initially increased in the first three years following HT (+0.12 per year, P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P <0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mTOR inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (p <0.001), hypertension (P <0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4, P <0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9, P <0.001) was associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. Conclusion: MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk factor modification and treatment with higher-intensity statin therapy and MTI are associated with a higher MFR.