Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications

Abstract

Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy (CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries (50-20 μm), arterioles (20-10 μm), and capillaries (< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcirculatory resistance during maximal hyperemia, which is calculated by dividing pressure by flow (distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.

Keywords: Heart transplantation, Cardiac allograft vasculopathy, Microvascular function, Coronary flow reserve, Endothelial dysfunction

Core tip: In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction in heart transplantation recipients, including an extended citation of relevant data from the literature. We think that this manuscript could be of interest for many research workers and physicians working in the field of cardiovascular surgery, cardiology and transplant medicine.