Cardiac allograft vasculopathy

Cardiac Allograft Vasculopathy (CAV) is a complex and multifactorial disease process that affects the coronary arteries of heart transplant recipients. It is characterized by diffuse coronary artery narrowing caused by intimal thickening, which can lead to ischemic heart disease, graft failure, and death. CAV is a significant cause of morbidity and mortality in the post-transplant period, and its management requires a multidisciplinary approach.

Etiology and Pathogenesis

The exact cause of CAV is not fully understood, but it is believed to be the result of both immune and non-immune factors. Immune factors include acute and chronic rejection episodes, while non-immune factors encompass traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes, and smoking, as well as specific transplant-related factors like cytomegalovirus (CMV) infection and the use of calcineurin inhibitors.

The pathogenesis of CAV involves endothelial injury and dysfunction, leading to an inflammatory response, smooth muscle cell proliferation, and extracellular matrix deposition. This process results in intimal thickening and narrowing of the coronary arteries, which impairs myocardial perfusion.

Clinical Presentation

CAV can be asymptomatic in its early stages due to the denervated status of the transplanted heart, which can mask typical angina symptoms. As the disease progresses, patients may present with heart failure symptoms, arrhythmias, or sudden cardiac death. Given the insidious onset and progression of CAV, regular monitoring through coronary angiography or other imaging modalities is critical for early detection.

Diagnosis

The diagnosis of CAV is primarily based on coronary angiography, which can reveal diffuse coronary artery narrowing. Intravascular ultrasound (IVUS) is a more sensitive tool that can detect early intimal thickening before angiographic changes become apparent. Other non-invasive imaging techniques, such as cardiac computed tomography (CT) angiography and magnetic resonance imaging (MRI), are also useful in assessing coronary artery anatomy and myocardial perfusion.

Treatment

The management of CAV focuses on the modification of risk factors, immunosuppressive therapy adjustment, and revascularization procedures. Statins are used for their lipid-lowering effects and potential immunomodulatory properties. Optimization of immunosuppression may involve increasing the doses of existing drugs or switching to alternative agents. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered for significant stenoses, although their efficacy is limited by the diffuse nature of the disease. In advanced cases, retransplantation may be the only option.

Prevention

Preventive strategies for CAV include aggressive management of cardiovascular risk factors, careful selection of immunosuppressive regimens, and monitoring for and treatment of CMV infection. Early detection through regular imaging surveillance is also crucial for the timely initiation of treatment.

Prognosis

The prognosis of patients with CAV is poorer than those without the disease, with increased risks of graft loss and death. The severity of coronary artery narrowing and the presence of cardiac allograft dysfunction are important prognostic indicators.