PET Assessment of Epicardial Intimal Disease and Microvascular Dysfunction in Cardiac Allograft Vasculopathy

Abstract

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure and death after heart transplantation. Absolute myocardial blood flow (MBF) quantification using rubidium 82 (Rb-82) positron emission tomography (PET) could enable evaluation of diagnostically challenging diffuse epicardial and microvascular disease in CAV.

Objectives: The authors aimed to evaluate Rb-82 PET detection of CAV.

Methods: Consecutive transplant recipients undergoing coronary angiography were prospectively evaluated with PET, multivessel intravascular ultrasound (IVUS), and intracoronary hemodynamics. CAV was defined as International Society of Heart and Lung Transplantation CAV_1-3 on angiography and maximal intimal thickness ≥0.5 mm on IVUS.

Results: Forty patients (mean age 56 years, 4.8 years post-transplant) completed evaluation. CAV was detected in 32 patients (80%) by IVUS and 14 (35%) by angiography. PET correlated significantly with invasive coronary flow indices: r = 0.29, rate-pressure product-adjusted myocardial flow reserve (cMFR) versus coronary flow reserve; r = 0.28, relative flow reserve versus fractional flow reserve; and r = 0.37, coronary vascular resistance (CVR) versus index of microcirculatory resistance. Patients with CAV or microvascular dysfunction had reduced cMFR and stress MBF and increased CVR. Receiver operator characteristic curves demonstrated good accuracy of PET for CAV on IVUS (area under the curve 0.77 to 0.81) and optimal diagnostic cutoffs of cMFR <2.9, stress MBF <2.3, and CVR >55. Combined PET assessment for CAV yielded excellent >93% sensitivity (>65% specificity) for 1 abnormal parameter and >96% specificity (>55% sensitivity) for 2 abnormal parameters.

Conclusions: Rb-82 PET flow quantification has high diagnostic accuracy for CAV, with potential for noninvasive evaluation after heart transplantation.

Keywords: cardiac allograft vasculopathy; flow quantification; flow reserve; heart transplantation; intravascular ultrasound; positron emission tomography.