Can Grading of Mild Cardiac Allograft Vasculopathy be Further Refined? An angiographic and physiologic assessment of heart transplant recipients with ISHLT CAV 1

Background: Cardiac allograft vasculopathy (CAV) results in impaired blood flow in both epicardial vessels and the microvasculature and is a leading cause of poor outcomes in heart transplant (HT) recipients. Most patients have mild (ISHLT CAV 1) disease. This study examined outcomes amongst those with ISHLT CAV 1 and investigated the value of physiologic assessment via cardiac positron emission tomography/computed tomography (PET/CT) for added risk stratification.

Methods: CAV was graded using ISHLT criteria. Those with CAV 1 were further sub-grouped into CAV 1a (maximal lesion < 30% stenosis) or CAV 1b (maximal lesion ≥ 30% stenosis).

Results: 299 heart transplant recipients underwent invasive coronary angiography for CAV assessment with median follow up 4.7 years. ISHLT CAV 1 was associated with a 2.9-fold risk of death/re-transplantation compared to ISHLT CAV 0 (95% CI 1.7 -5.3, p<0.001). Of those with ISHLT CAV 1, 12% had ISHLT CAV 1b which was associated with a 2.8 times greater risk of death/re-transplantation compared to CAV 1a (95% CI 1.4-5.9, p=0.003). In a subgroup of 158 patients with contemporary cardiac PET/CT, amongst those with CAV 1a a myocardial blood flow reserve (MBFR) ≤ 2 was associated with a 4.6-fold risk of death/re-transplantation compared to a normal MBFR (95% CI 1.7-12.6, p=0.001).

Conclusion: Patients with ISHLT CAV 1 fared worse than those with ISHLT CAV 0. Within ISHLT CAV 1, patients with CAV 1b had worse outcomes than those with CAV 1a. Amongst those with CAV 1a, the poorer outcomes than ISHLT CAV 0 observed were predominantly associated with reduced MBFR. These data suggest additional anatomic classification and physiologic assessment can further risk stratify those with ISHLT CAV 1.