Cardiac Positron Emission Tomography in Cardiac Allograft Vasculopathy (PETCAV study)
UOH-15-006 This study determined previously unknown diagnostic thresholds for cardiac allograft vasculopathy (CAV) using rubidium-82 positron emission tomography (PET). We have recently successfully validated our results. Furthermore, we developed a potential clinical PET diagnostic algorithm to guide invasive coronary testing. Preliminary results from the PETCAV study were presented at the 2016 Canadian Cardiovascular Congress and 2017 International Society of Heart and Lung Transplantation, and our manuscript was published in the Journal of the American College of Cardiology (2018). In addition, through funding from the 2016 Canadian Transplant Research Program Innovations Grant competition, we performed a biomarker discovery substudy, and have recently submitted the results for publication. The findings from the PETCAV study determined methodology for an ongoing multicentre study (ECAV) investigating advanced cardiac imaging tools for comprehensive evaluation of CAV. This study received funding support through a Grant in Aid from the Heart and Stroke Foundation as well as University of Ottawa Heart Institute ORACLE Team Grant.
UOH-15-006 BACKGROUND: Cardiac allograft vasculopathy (CAV) is an accelerated fibroproliferative arteriopathy, affecting 1 in 2 heart transplant recipients and reducing long-term graft survival. Current non-invasive imaging techniques for diagnosis of CAV are insensitive, particularly for detection of early coronary intimal disease. The objective of this study was to assess rubidium-82 positron emission tomography (Rb82 PET) myocardial blood flow (MBF) quantification for CAV alongside comprehensive invasive evaluation of coronary anatomy and physiology. METHODS: Consecutive heart transplant patients were evaluated by PET, coronary angiography, multivessel intravascular ultrasound (IVUS) and intracoronary hemodynamics. CAV was defined by angiography and IVUS. RESULTS: Forty patients (mean age 56 years, 4.8 years post-transplant) completed evaluation. CAV was detected in 32 (80%) patients by IVUS and 14 (35%) patients by angiography. There was significant correlation between PET myocardial flow and invasive coronary flow indices. Patients with CAV had reduced PET myocardial flow reserve (MFR), stress MBF, and increased coronary vascular resistance (CVR). Receiver operator characteristic curve analysis demonstrated high discriminative ability of PET for CAV: area under curve 0.77 for MFR, 0.78 for stress MBF, 0.81 for CVR. Optimal PET diagnostic cut-offs for CAV of MFR <2.9, stress MBF <2.3 and CVR >55 were determined and combined assessment of any 2 parameters yielded high >93% sensitivity and >96% specificity for CAV. CONCLUSIONS: Our results validate the use of Rb82 PET myocardial flow quantification as surrogate measures of invasive coronary flow in heart transplant patients. PET flow quantification has high diagnostic accuracy for CAV with potential for noninvasive evaluation after heart transplantation.