PET/CT with Myocardial Blood Flow Assessment Is Prognostic of Cardiac Allograft Vasculopathy Progression and Clinical Outcomes

Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial vessels and microvasculature and remains a leading cause of posttransplant morbidity and mortality. This study examined the prognostic value and outcomes of CAV, assessed by ¹³N-ammonia PET/CT myocardial perfusion imaging in heart transplant recipients. <b>Methods:</b> PET/CT and invasive coronary angiography (ICA) were graded using validated scales. CAV progression was assessed using intrapatient sequences: baseline ICA, interval PET/CT with myocardial blood flow reserve, and subsequent ICA. Intervals between ICAs of 600, 900, and 1200 d were included, and for each, the negative predictive value (NPV) of CAV development was assessed. <b>Results:</b> In total, 344 heart transplant recipients underwent PET/CT for CAV assessment with a median follow-up of 4.8 y. PET CAV grade 0/1 had an NPV of 0.93, 0.95, and 0.95 at each respective time point for developing an International Society for Heart and Lung Transplantation CAV 2/3 on subsequent ICA. Compared with PET CAV 0, PET CAV 2/3 was associated with a 2.9-fold increased risk of all-cause mortality (hazard ratio, 2.86; 95% CI, 1.36-6.00; <i>P</i> = 0.006). PET CAV 1 had a numerically increased risk (hazard ratio, 2.03; 95% CI, 0.99-4.15; <i>P</i> = 0.054). In a sensitivity analysis of 135 patients with stable International Society for Heart and Lung Transplantation CAV over successive ICA, PET CAV 2/3 remained associated with increased risk of death or retransplantation (hazard ratio, 3.20; 95% CI, 1.18-8.69; <i>P</i> = 0.03). <b>Conclusion:</b> Noninvasive CAV assessment by PET/CT and myocardial blood flow reserve provides prognostic information and robust NPVs for development of moderate to severe CAV over intervals up to 4 y. These data suggest that, for certain patients, intervals between invasive screenings may be extended.