Heart transplantation—An update

Abstract

Summary:Cardiologists caring for heart transplant recipients must be familiar with the pharmacology, drug interactions, and drug toxicity of those agents used extensively in clinical practice (cyclosporine, prednisone, azathioprine, pol yclonal and monoclonal anti-T-cell agents) and the newer treatments [methotrexate, FK-506, rapamycin, mycophenolate mofetil (RS6 1443), deoxyspergualin, anti-CD4 monoclonal antibodies, total lymphoid irradiation, and photophoresis]. Another important aspect of medical follow-up is the detection, differential diagnosis, and treatment of allograft dysfunction. Hemodynamic abnormalities that occur as a result of rejection or a direct drug effect must be differentiated from physiologic changes. Cardiac allograft vasculopathy is the primary impediment to the long-term survival of heart transplant recipients. Immunopathogenesis, prevention, early detection, and treatment of allograft vasculopathy should be the major focus of heart transplantation research.

Cardiovascular Toxicities of Immunosuppressive Agents

“…Hypertension occurs in 50% to 100% of transplant recipients (8–11). The prevalence of hypertension increases with time after transplantation, from 52% at 1 year to 77% at 4 years (10).…”

“…Dyslipidemia, a common finding following transplantation, occurs in more than 80% of heart‐, 60% to 70% of renal‐, and 45% of liver‐transplant recipients receiving immunosuppressive therapy (7–9,31–33). The specific lipid fractions that are abnormal vary among organ recipients, but increased low‐density lipoprotein (LDL) cholesterol, decreased high‐density lipoprotein (HDL) cholesterol, and increased triglyceride levels are common after heart transplantation.…”

“…Mechanisms. Despite the prevalence and adverse clinical consequences of CAH, the precise mechanism(s) are unknown; however, several potential mechanisms have been proposed (Table 1) (8,9,14). Twenty‐four‐hour recordings after heart transplantation have demonstrated that, unlike essential hypertension, CAH may be common at night due to cardiac denervation, a persisting increase in systemic vascular resistance, and an absence of the normal decrease in heart rate and cardiac output seen in nontransplantation patients.…”

“…Mechanisms of steroid‐induced dyslipidemia. It has been suggested that corticosteroid‐induced dyslipidemia is a result of weight gain, which leads to insulin resistance, increased hepatic secretion of very low‐density lipoprotein (VLDL), and increases in total cholesterol and triglyceride levels (9,31,39). Increases in VLDL, total cholesterol, and triglyceride levels and a decrease in HDL cholesterol level with corticosteroid immunosuppression are a result of several effects of corticosteroids: enhanced activity of acetyl‐coenzyme A carboxylase and free fatty acid synthetase, increased hepatic synthesis of VLDL, down‐regulation of LDL receptor activity, increased activity of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase, and inhibition of lipoprotein lipase (32).…”

A Retrospective Analysis of Ezetimibe Treatment in Renal Transplant Recipients

“…In addition to the traditional risk factors for CVD, renal transplant recipients have other risks associated with impaired kidney function and also those associated with many immunosuppressive agents (6,7). After transplantation, the most significant rise in total cholesterol (TC) occurs in the first 3–6 months post‐transplantation resulting in approximately 70% of renal transplant recipients developing dyslipidemia (1,6–12).…”