Accelerated Cardiac Allograft Vasculopathy: A Clinical and Pathologic Correlation Study

Purpose Cardiac allograft vasculopathy (CAV) is a prevalent cause of graft failure and has remained so despite advances in HLA matching and immunosuppression in recent decades. Several distinct pathologic phenotypes of CAV have been described (Lu et al JHLT 2011 and Huibers et al Atherosclerosis 2014), but the correlation of these phenotypes to clinical features has been limited. Of particular interest in this study are patients who develop accelerated CAV, since this presentation is so clinically devastating but also because it may provide important mechanistic insights into CAV initiation and progression. Methods Patients with accelerated development of CAV were identified from the transplant and pathology databases of the UTAH Cardiac Transplant Program. Dates of transplant, last normal angiogram, and explant or autopsy were collected along with demographic and pertinent clinical information. Histopathologic features of their allograft coronary arteries were systematically collected. The pathologic and clinical features were compared. Results Five patients with accelerated CAV development were identified. Their details are shown in the table below. Four of the patients had a normal angiogram within a mean of one year from graft loss, but all showed diffuse >75% coronary narrowing by pathology (see image below). The CAV phenotypic features observed histologically included prominent active vasculitis (intimal and transmural) and shallow mural thrombus. In 2 cases mural thrombus appeared to be incorporated into the intimal proliferative process (see #3-high). Peri-adventitial inflammation was also a prominent feature in 4 of the patients. Conclusion Accelerated CAV is uncommon, but also unpredictable. From this series of patients, it appears CAV can progress from being undetectable by angiography to critical stenosis and graft failure in as little as 4 months (mean 1 year). Vascular inflammation and shallow mural thrombus play a key role in this rapid progression. Cardiac allograft vasculopathy (CAV) is a prevalent cause of graft failure and has remained so despite advances in HLA matching and immunosuppression in recent decades. Several distinct pathologic phenotypes of CAV have been described (Lu et al JHLT 2011 and Huibers et al Atherosclerosis 2014), but the correlation of these phenotypes to clinical features has been limited. Of particular interest in this study are patients who develop accelerated CAV, since this presentation is so clinically devastating but also because it may provide important mechanistic insights into CAV initiation and progression. Patients with accelerated development of CAV were identified from the transplant and pathology databases of the UTAH Cardiac Transplant Program. Dates of transplant, last normal angiogram, and explant or autopsy were collected along with demographic and pertinent clinical information. Histopathologic features of their allograft coronary arteries were systematically collected. The pathologic and clinical features were compared. Five patients with accelerated CAV development were identified. Their details are shown in the table below. Four of the patients had a normal angiogram within a mean of one year from graft loss, but all showed diffuse >75% coronary narrowing by pathology (see image below). The CAV phenotypic features observed histologically included prominent active vasculitis (intimal and transmural) and shallow mural thrombus. In 2 cases mural thrombus appeared to be incorporated into the intimal proliferative process (see #3-high). Peri-adventitial inflammation was also a prominent feature in 4 of the patients. Accelerated CAV is uncommon, but also unpredictable. From this series of patients, it appears CAV can progress from being undetectable by angiography to critical stenosis and graft failure in as little as 4 months (mean 1 year). Vascular inflammation and shallow mural thrombus play a key role in this rapid progression.