Coronary microvascular dysfunction by positron emission tomography and outcomes in patients after cardiac transplantation without epicardial allograft vasculopathy

Cardiac allograft vasculopathy (CAV) affects both epicardial and microvascular coronary arteries, however few studies have characterized microvascular dysfunction in this population. Several prior studies have shown positron emission tomography/computed tomography (PET/CT) can be used to screen for epicardial CAV, however the clinical implications of abnormal blood flow in the absence of epicardial CAV is unknown. Our study sought to assess the prognostic implications of microvascular dysfunction and its sub-types, endogen/functional and classical/structural, using PET/CT in cardiac transplant patients without epicardial CAV. Transplant patients with no prior history of CAV and normal myocardial perfusion imaging were included. Patients were then classified by the presence of microvascular dysfunction (CMD) (MFR <2.0); patients with CMD were further subcategorized into endogen/functional (stress myocardial blood flow ≥1.7 mL/min/g) and classical/structural (stress myocardial blood flow <1.7 mL/min/g). The primary outcomes were all-cause mortality and a composite of all-cause mortality, heart failure hospitalization, acute coronary syndrome, revascularization, and re-transplantation. 356 patients met the inclusion criteria. CMD was present in 141 (39.6%) patients, of which 112 (31.4%) had endogen/functional CMD and 29 (8.1%) had classical/structural CMD. After multivariable adjustment, endogen/functional CMD was associated with a higher rate of the composite outcome (HR 2.39, 95%CI 1.32-4.29, p = 0.004) and all-cause mortality (HR 2.98, 95%CI 1.34-6.64, p = 0.008). Classical/structural CMD was not associated with the primary composite outcome (HR 0.92, 95%CI 0.27-3.17, p = 0.893) or all-cause mortality (HR 1.22, 95%CI 0.263-5.69, p = 0.797). In cardiac transplant patients with no history of CAV and normal myocardial perfusion, an endogen/functional pattern of CMD is associated with higher rate of adverse events and death. This association was not present in patients with a classical/structural CMD pattern. Incorporating endogen/microvascular dysfunction assessment in PET/CT reporting may identify a higher risk group hereto now considered low risk.