Assessment of late-term progression of cardiac allograft vasculopathy in patients with orthotopic heart transplantation using quantitative cardiac 82Rb PET.

Abstract

The risk stratification and long-term survival of patients with orthotopic heart transplantation (OHT) is impacted by the complication of cardiac allograft vasculopathy (CAV). This study evaluates changes in myocardial blood flow (MBF) and myocardial coronary flow reserve (CFR) in a group of long-term OHT patients using quantitative cardiac 82Rb-positron emission tomography (PET). Twenty patients (7 females and 13 males, mean age = 72.7 ± 12.2years with CAV and 62.9 ± 7.2years without CAV and post-OHT mean time = 13.9years), were evaluated retrospectively using dynamic cardiac 82Rb-PET at rest and regadenoson-induced stress. The patients also underwent selective coronary angiography (SCA) for diagnosis and risk stratification. CAV was diagnosed based on SCA findings and maximal intimal thickness greater than 0.5mm, as defined by International Society of Heart and Lung Transplantation (ISHLT). Global and regional MBFs were estimated in three vascular territories using the standard 1-tissue compartment model for dynamic 82Rb-PET. The myocardial CFR was also calculated as the ratio of peak stress MBF to rest MBF. Among twenty patients, seven had CAV in, at least, one major coronary artery (ISHLT CAV grade 1 or higher) while 13 patients did not have CAV (NonCAV). Mean rate-pressure products (RPP) at rest were significantly elevated in CAV patients compared to those without CAV (P = 0.002) but it was insignificant at stress (P = NS). There was no significant difference in the stress MBFs between CAV and NonCAV patients (P = NS). However, the difference in RPP-normalized stress MBFs was significant (P = 0.045), while RPP-normalized MBFs at rest was not significant (P = NS). Both CFR and RPP-normalized CFR were significantly lower in CAV compared to NonCAV patients (P < 0.001). There were significant correlations between MBFs and RPPs at rest for both CAV (ρ = 0.764, P = 0.047) and NonCAV patients (ρ = 0.641, P = 0.017), while there were no correlations at stress for CAV (ρ = 0.232, P = NS) and NonCAV patients (ρ = 0.068, P = NS). This study indicates that the resting MBF is higher in late-term post-OHT patients. The high resting MBF and reduced CFR suggest an unprecedented demand of blood flow and blunted response to stress due to impaired vasodilatory capacity that is exacerbated by the presence of CAV.