Introduction: Cardiac allograft vasculopathy (CAV) is the major determinant of late mortality in heart transplant (HT) patients. Given the global epicardial and microvascular involvement in CAV, myocardial blood flow (MBF) quantification by positron emission tomography (PET) holds great promise for the noninvasive assessment of CAV, but currently limited data is available regarding the prognostic value.
Methods: Ninety-two patients with history of HT (71% men, 7.1±5.6 years post HT, age: 57±11 years) scheduled for dynamic 82Rubidium PET during 05/2008 to 07/2009 were prospectively enrolled in a single center study. Imaging was performed on a whole body 2D/3D PET and 16-slice CT scanner (Discovery ST, GE Healthcare). Dynamic rest and dipyridamole or regadenoson stress PET studies were reprocessed using FDA approved software (Corridor 4DM v2017, INVIA) for calculation of absolute MBF and coronary flow reserve (CFR). Rest and stress flows were corrected for rate pressure product. In a subset of patients (n=38) left heart catheterization (LHC) with (30/38) or without (8/38) intravascular ultrasound (IVUS) was performed within 24±5 days of PET. Patients were assessed for all-cause mortality.
Results: A weak, but significant inverse relationship was observed between global CFR and time-interval since HT (r=-0.27, 95% confidence interval [CI]: -0.45 to -0.07, p=0.009). Severely reduced CFR (CFR≤1.5) was detected in 27 patients. During the median follow-up time of 8.5 years 40 deaths occurred. Severely reduced CFR (CFR≤1.5) was associated with a 3-fold increase in risk of all-cause mortality (95%CI: 1.13-7.59; P=0.03) compared with normal CFR (CFR>2, Fig 1). CFR was significantly lower in patients diagnosed with CAV by LHC or IVUS compared to patients without CAV (CFR: 1.8±0.16 vs. 2.4±0.14, p=0.007).
Conclusions: CFR assessed by 82Rubidium PET predicts mortality in HT recipients and provides a noninvasive diagnostic tool for the assessment of CAV.