Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation.

AIMS: Data on the safety and efficacy of HMG CoA reductase inhibitors in managing dyslipidemia in heart transplant recipients is inadequate. We undertook this study to evaluate the comparative safety and efficacy of simvastatin and pravastatin in lowering lipids in heart transplant recipients. METHODOLOGY: Forty eight patients (38 males) who received heart transplantation between 1995 and 1997, and who had no contraindications to statin therapy or history of myopathy were randomized to receive either pravastatin (n=24) or simvastatin (n=24) for six months. Detailed fasting lipid profiles, hepatic function tests, and serum creatinine phosphokinase were obtained regularly. Baseline and six month characteristics were compared using the unpaired student t test for continuous variables and Chi-square analysis or Fisher's exact test, as appropriate. RESULTS: Baseline total cholesterol levels, LDL cholesterol levels, HDL cholesterol levels, and triglyceride levels were similar in the two groups. At six months, the total cholesterol, LDL cholesterol, and triglyceride levels were greatly reduced in both groups, with greater reductions in the simvastatin group than in the pravastatin group. Only modest increases were noted in HDL cholesterol levels in the two groups. No significant adverse effects were noted, and no complications with drug withdrawals occurred. Patient compliance exceeded 97%. CONCLUSION: Simvastatin and pravastatin are safe and very effective in total cholesterol and LDL cholesterol lowering in heart transplant recipients, with simvastatin being more efficacious than pravastatin in lipid lowering in this group of patients.

The unique management of refractory advanced systolic heart failure.

Advanced systolic heart failure refractory to ambulatory pharmacotherapy continues to be a clinical dilemma with increasing incidence and prevalence. By establishing the presence of signs and symptoms, clinicians could better evaluate hemodynamic perturbations, therefore targeting them through the use of intravenous diuretics, intravenous vasodilators, and intravenous inotropic therapy. This review focuses on the unique features that characterize advanced heart failure, and discusses the special clinical considerations in managing this morbid entity.

Myoblast transplantation in the porcine model: a potential technique for myocardial repair.

The use of transgenic cells transplanted in syngeneic rodents has shown modest success, but allogeneic and xenogeneic transplants have not been uniformly successful. To assess the feasibility of xenogeneic and allogeneic myoblast transplantation, we subjected seven adult swine to transplantation of murine atrial tumor cells (xenogeneic), neonatal porcine myocytes (allogeneic), and human fetal cardiomyocytes into the left ventricular wall. After general anesthesia, isolated cells were injected along the anterior and posterior walls of the porcine left ventricle. All the animals were immuno-suppressed and observed for 1 month after injection, at which time they were killed and analyzed. This report will present results primarily concerned with the success of human cell transfers. In all injected sites examined, the transplanted cells thrived within the host myocardium with no significant rejection. Transplant cells formed close associations with host myocytes that resembled nascent intercalated disks on electron microscopy. These cells also contained myofibrils and other cell architecture resembling the transplanted cell lines. Additionally, these cells appeared to produce an angiogenic influence resulting in the proliferation of the surrounding microvasculature. We believe that these findings indicate successful xenogeneic and allogeneic myoblast cell transplantation in a large animal model. These experiments set the stage for future studies to assess the ability of these cells to form a syncytium, contract, and potentially repair failed myocardium.

High-risk surgery as an alternative to transplantation.

Between April 1992 and April 1994, 185 patients were waiting for a cardiac transplant at our institution. Transplantation was performed in 118 of these patients. Twenty-six patients (14%) died while awaiting a donor heart: 13 of these were in the intensive care unit on multiple inotropic medications, mechanical support, or both; another 13 were either in the hospital on a single inotropic medication or at home with or without inotropic support. The remaining 41 patients were still awaiting transplantation at the end of the study period. During the same interval, 20 comparably ill patients who were referred to our institution for transplantation were considered for high-risk conventional surgical procedures. These patients underwent clinical evaluation to determine whether they had viable muscle that was salvageable and electrophysiologic status that was alterable. On this basis, these 20 patients underwent a variety of combined high-risk procedures. Two patients died; the operative mortality was 5% and the cumulative mortality was 10%. We conclude that these initial results support our original impression that mortality rates are higher in patients waiting for cardiac donation than in patients undergoing high-risk surgical procedures. Therefore, we will continue to investigate high-risk conventional surgery as an alternative to cardiac transplantation.