Lack of sensitization and equivalent post-transplant outcomes with the Novacor left ventricular assist device.

BACKGROUND: Ventricular assist devices (VADs) are increasingly used to support critically ill heart failure patients awaiting transplantation. Previous work has focused on the Thoratec Heartmate VE device, use of which is associated with pre-formed antibody production. We reviewed our cumulative experience with the Worldheart Novacor VAD as a bridge to transplantation (BTT). METHODS: From January 1989 through October 2002, 39 patients required a VAD bridge, with 26 of 39 surviving to transplantation. Antibody levels were assessed by complement-dependent cytotoxicity assay at routine intervals and expressed as panel reactive antibody (PRA) levels. Post-transplant allograft rejection, coronary vasculopathy, and survival were compared between Novacor-supported patients and non-VAD transplant recipients. RESULTS: PRA values did not significantly change after VAD implantation (12.4% +/- 11.2% vs 14.8% +/- 12.3%, p = 0.28). Survival for the BTT patients was 80.4%, 75.7%, 64.0%, 64.0%, and 64.0%, respectively, for 1, 3, 5, 7, and 10 years post-transplant, with similar results for non-BTT patients. The freedom from coronary vasculopathy was 90.2%, 90.2%, 72.2%, and 72.2%, respectively, at 1, 3, 5, and 7 years post-transplant. CONCLUSIONS: First, to our knowledge, this study is the first to examine the incidence of allosensitization after Novacor implant in detail. In contrast with previous results of work with other VAD systems, as assessed by PRA levels, Novacor patients did not become sensitized. Second, compared with 220 non-BTT patients who received transplants during a similar time frame, Novacor BTT patients had equivalent rejection profiles and survival. Finally, the incidence of transplant-associated coronary artery disease was lower than in previous reports.

Recent improvements in outcome with the Novacor left ventricular assist device.

BACKGROUND: The Novacor implantable, electrically powered, wearable, left ventricular assist device (LVAD) has been used as a bridge to transplantation at our institution since 1994. Recent changes in protocol have resulted in a decreased incidence of infections, thromboembolism, and mortality. METHODS: We reviewed the medical records of all 43 patients who received implantable LVADs at the Mount Sinai Medical Center. After 1998, a number of protocol modifications were instituted. Vascular grafts were changed from a low-porosity, woven polyester (Cooley) to a gelatin-sealed, knitted polyester graft (Vascutek), the devices were implanted pre-peritoneally rather than in the posterior rectus sheath, and extensive drainage of the chest and pre-peritoneal pocket was used. The following anti-coagulation regimen was used: low-molecular-weight Dextran for 1 day, initiated after chest tube drainage <50 cc/hour; then IV heparin for 10 to 14 days, beginning at 500 U/hour, slowly increasing partial thromboplastin time to 1.5 to 2 x control; and finally Coumadin, maintaining the international normalized ratio at 2.5 to 3.5. Daily aspirin, 325 mg, was begun on post-operative Day 7. We compared 22 patients who electively underwent surgery before the changes, Group I, with 18 patients treated thereafter, Group II. RESULTS: Groups I and II were well matched with regard to age (47 vs 44 years); cause of heart failure (idiopathic, 50% vs 44%; ischemic, 50% vs 56%), and duration of support (79 vs 76 days). The incidence of thromboembolic cerebrovascular events was significantly less in Group II (6%) than in Group I (23%), p = 0.025. The incidence of bleeding increased mildly in Group I. Pocket infections occurred in 27% of Group I patients vs 11% of Group II patients, p = 0.018. Only 2 patients (11%) in Group II died while receiving device support, vs 7 (32%) in Group I, p = 0.019. CONCLUSIONS: Our results indicate that pre-peritoneal implantation, use of a new generation of vascular grafts, extensive drainage, and a more restricted anti-coagulation regimen improve outcome after Novacor LVAD implantation for advanced heart failure.

Tacrolimus in cardiac transplantation: efficacy and safety of a novel dosing protocol.

BACKGROUND: Although used for more than 20 years, optimal dosing strategies of most immunosuppressants have never been determined. Tacrolimus, one of the newer agents used in solid-organ transplantation, is gaining increasing popularity because of its ability to reverse refractory rejection in cyclosporine-treated patients and its favorable side-effect profile. As with many other immunosuppressive agents, absorption and metabolism vary between individuals, which complicates dosing. METHODS: We hypothesized that a 1-mg dose of tacrolimus may be used to gauge each patient's metabolism. A novel dosing scheme was evaluated to establish the safety and efficacy of this approach. Outcomes were incidence of renal insufficiency and treatment efficacy as assessed by the rejection grade on the first endomyocardial biopsy. RESULTS: The risk of renal insufficiency was low, with only a 3% rise in creatinine at 7 days posttransplant. The risk of renal insufficiency was highest during the first 3 days of tacrolimus therapy, and the change in tacrolimus level during this time was identified as the single best predictor of renal insufficiency. From days 4 to 7, the rise in tacrolimus level had much less influence on renal function. Ninety-two percent of patients had a low- or intermediate-grade first cardiac biopsy. CONCLUSIONS: It was shown that this conservative initial dosing approach, which guarantees renal safety, is not associated with an increased risk of allograft rejection. We conclude that administration of tacrolimus via a tailored protocol soon after transplantation ensures a safe and effective means of immunosuppression.