Cardiac Allograft Vasculopathy: A Focus on Advances in Diagnosis and Management

Abstract

Cardiac allograft vasculopathy (CAV) is a type of coronary artery disease unique to heart transplant recipients that can result from chronic rejection of the transplanted heart. CAV is a major cause of morbidity and mortality after the first year of transplantation. Both immune and nonimmune mechanisms contribute to the initiation and progression of CAV and result in intimal thickening, fibrosis with luminal stenosis, chronic myocardial ischemia and eventual graft failure. Recent advances in imaging modalities-including invasive intracoronary imaging and noninvasive imaging with cardiac positron emission tomography-have improved the early detection of CAV and may allow for optimization of CAV-targeted therapies to reduce CAV progression and ultimately preserve graft function.

Keywords: IVUS; PET; coronary angiography; heart transplant; mTORi; rejection; vasculopathy.

Figure 1

Risk factors and treatment of cardiac allograft vasculopathy. Multiple immune risk factors and nonimmune risk factors contribute to the development and progression of cardiac allograft vasculopathy (CAV), which is defined by intimal hyperplasia due to immune infiltration and immune signaling/activity, myofibroblast proliferation, and collagen deposition, ultimately restricting coronary luminal diameter. CMV: cytomegalovirus; mTORi: mammalian target of rapamycin inhibitors (including sirolimus and everolimus); ASA: aspirin; PCI: percutaneous coronary intervention. Image created with Biorender

Figure 2

Diagnostic algorithm for the surveillance of cardiac allograft vasculopathy (CAV) post-transplantation. This is an adaptation of the CAV surveillance protocol at our institution. Following heart transplantation, CAV screening typically starts at 1-year post-transplantation with coronary angiography with IVUS to assess for early CAV. Early coronary angiography between 4 weeks and 3 months post-transplantation can be considered if there are risk factors for donor-derived coronary artery disease. For patients with ISHLT grade 0 or Stanford classification 1 CAV (see Table 1), optimization of statin therapy and immunosuppression is preferred. These patients are screened for progression of CAV with serial noninvasive imaging, such as cardiac PET (alternatives include cardiac MRI or stress echocardiography, depending on institutional expertise). If serial cardiac PET imaging reveals ischemia or reduced myocardial flow reserves, patients undergo coronary angiography with or without IVUS. When ISHLT grade 1-3 or Stanford classification 2-4 CAV is detected, mTOR inhibition is considered, PCI may be performed for symptomatic, focal, lesions, and serial imaging is continued with either coronary angiography or cardiac PET imaging. Certain special considerations are listed above. CAV: cardiac allograft vasculopathy; IVUS: intravascular ultrasound; ISHLT: International Society for Heart and Lung Transplantation; PET: positron emission tomography; mTOR: mammalian target of rapamycin; PCI: percutaneous coronary intervention. Image created with Biorender