Atrial masses post cardiac transplantation: diagnostic and treatment dilemmas.

Atrial masses postcardiac transplant are not well reported and their diagnosis and treatment can be challenging. In the asymptomatic patient, differentiating thrombus from cardiac tumor can sometimes be difficult and the use of multiple imaging modalities is recommended. Accurate diagnosis is imperative to inform a treatment plan that balances the benefits and risks of a medical versus surgical approach. We present three cases of atrial masses postcardiac transplant to illustrate this clinical dilemma.

Impact of adjuvanted H1N1 vaccine on cell-mediated rejection in heart transplant recipients.

During the H1N1 influenza virus pandemic, vaccination of high risk groups including solid-organ transplant recipients was advised. A retrospective case control study of 60 heart transplant patients, 15 having received the H1N1 virus antigen and ASO3 adjuvant vaccine (GlaxoSmithKline, Mississauga, ON, Canada) within 21 days and 45 having not been vaccinated, all undergoing routine surveillance endmyocardial biopsies, was performed. The overall rate of cellular rejection (all grades) was not statistically different between groups; however, acute cellular rejection, ≥grade 2 (1990 ISHLT criteria), was more frequent among those having recently vaccinated (control: 1/45 vs. 6/15, p = 0.001). On multivariate analysis, the only risk factor found to be associated with acute cellular rejection was recent H1N1 viral antigen and adjuvant vaccination (OR 26.5: 95% CI 02.59-270.5). Vaccine adjuvants increase host response to vaccine antigens by immune upregulation potentially increasing risk of rejection in solid-organ transplant recipients. The potential hazard of vaccination this study raises must be weighed with the clear benefit vaccination has proven to be.

Patent foramen ovale does not have a negative impact on early outcomes in patients undergoing liver transplantation.

OBJECTIVE: To identify the impact of the presence of patent foramen ovale (PFO) in patients undergoing liver transplantation. METHODS: Twenty-seven pre-liver transplant patients who had a PFO (PFO group) were identified and compared with 61 patients without PFO (NoPFO group). Patients were matched according to age, gender and cause of liver disease. The diagnosis of PFO was made by transthoracic echocardiography prior to liver transplantation. Patient baseline characteristics and complications during the early post-transplant period were analyzed. RESULTS: The mean age in the PFO group was 47 ± 14 (range 18-68) yr and 50 ± 11 (range 12-65) yr in the NoPFO group. The PFO group had a mean model for end-stage liver disease (MELD) score of 15 ± 10 whereas in the NoPFO group the MELD score was 19 ± 10 (p = 0.08). There were non-significant differences in echocardiographic parameters between groups. Duration of mechanical ventilation and the incidence of neurological complications were similar. Thirty-day mortality rate was similar in both groups; only one patient in the NoPFO group died within the first 30 days post-transplantation. CONCLUSIONS: The presence of PFO in patients with end-stage liver disease undergoing liver transplantation does not appear to affect patient outcomes during the peri-operative period.

The promise of C2, Simulect, and Certican in heart transplantation.

Immunosuppressive therapy in clinical transplantation has evolved from general nonspecific suppression of the immune system to selective blockade of intracellular immune events, maximizing graft tolerance while minimizing toxicity. Cyclosporine 2-hour postdose level monitoring has been recommended as the single most sensitive sampling point for assessment of the area under the curve, and predictor of clinical outcomes in heart transplantation. Strategies for monitoring immunosuppressive drugs to improve efficacy without increased toxicity are critical as we move into the 21st century. Everolimus, a derivative of rapamycin, is a macrocyclic immunosuppressive agent with antiproliferative activity that is efficacious in preventing graft vasculopathy. Agents that increase the armamentarium against rejection allowing individualized therapy tailored to minimize complications, and prevent graft vasculopathy will improve our flexibility and may translate into improved long-term outcomes.

Community support of patients with a left ventricular assist device: The Toronto General Hospital experience.

BACKGROUND: Implantation of a left ventricular assist device (LVAD) is an acceptable therapy for patients with advanced heart failure. LVADs may be used as a bridge to recovery, a bridge to transplantation or as destination therapy. Although the morbidity rate of individuals on device support remains high, experience suggests that patients who are discharged home have satisfactory outcomes during support and following heart transplantation. METHODS: A retrospective review of 24 patients implanted with an LVAD between October 2001 and December 2006 was performed. Nineteen patients received a device as a bridge to transplantation and five received a device as destination therapy. Postoperative follow-up was performed routinely in the heart function/LVAD clinic at the Toronto General Hospital (Toronto, Ontario) and all adverse events were recorded. RESULTS: The majority of patients were men, with a mean age of 44 years and a diagnosis of dilated cardiomyopathy (62%). Seventeen patients (71%) were discharged home on support; one died, 14 were transplanted, one was explanted and one patient remains on support in the community. Post-transplant survival was 93% in patients discharged home compared with 40% transplanted during their hospital stay. Outpatients spent 56% of their overall support time at home, with only 12 readmissions totalling 120 patient days. CONCLUSIONS: LVAD patients can be safely managed in the community. Patients who are discharged home experience better outcomes in both pre- and post-transplant survival. Successful outpatient management provides a strong foundation for the establishment of destination therapy within mechanical circulatory support programs in Canada.

mTOR inhibition induces endothelial progenitor cell death.

Immunosuppressants are necessary to prevent graft rejection after solid organ transplantation. However, they are also known to have significant side effects, including endothelial toxicity. Endothelial progenitor cells originate in the bone marrow and are recognized by their angiogenic and endothelial reparative properties. The effects of the immunosuppressants cyclosporine A (CyA), tacrolimus and rapamycin were analyzed on endothelial progenitor-like cells. Rapamycin induced rapid cell death, even at concentrations much lower than those used clinically, in peripheral blood mononuclear cells (PBMC) cultured to favor outgrowth of endothelial progenitors. Cyclosporine A and tacrolimus had no significant effects at clinical concentrations. The effect of rapamycin was specific to endothelial progenitor cells, in particular to the early stages of differentiation, as a lesser effect was observed in late outgrowth endothelial progenitors, mature aortic endothelial cells, and macrophages derived from the same PBMCs. The mechanism of cell death appeared to be apoptosis; however, its induction was probably multifactorial and did not depend on caspase or cathepsin activation. In conclusion, rapamycin induces endothelial progenitor cell death, possibly because it blocks survival signals given by growth factors critically required by these cells.

Should moderate acute rejection of a cardiac transplant graft be treated?

UNLABELLED: Histologically proven, moderate acute rejection after orthotopic heart transplantation (OHT) is commonly treated with intravenous steroids. This regimen may result in severe metabolic and infectious side-effects. The purpose of this study was to assess and compare outcomes in treated (T) versus not treated (N-T) biopsy proven 3A rejection episodes in cardiac transplant recipients. METHODS: A retrospective analysis was conducted to identify all biopsy proven 3A rejection episodes that occurred over the time period 1995-2000 in patients (patients) >or= 6 months after OHT (n=48 episodes in 35 patients). Of the 48 episodes, 19 were N-T and 29 were T. Decision to treat 3A rejection was based on time after transplant, haemodynamic and/or clinical compromise and left ventricular (LV) dysfunction measured by 2D echo. Most N-T episodes received an increase in background immunotherapy. RESULTS: Time from transplant to index 3A episode in N-T patients was 4.2 versus 2.7 yr for the T patients (p=0.06). There were no differences seen between T and N-T groups for the first and second post-3A biopsy results or LV function post-3A. Presence of coronary disease or death were not different between groups. Of the 29 patients with T episodes, no differences in outcomes (death, first and second post-3A biopsy score, coronary disease, myocardial infarction, or LV function) were seen based on use of treatment with intravenous versus oral steroid. CONCLUSION: In patients more than 6 month after OHT, there were no differences in outcomes (ongoing rejection or LV function) between N-T episodes of 3A rejection and T episodes. In T patients the use of oral steroids was equally as effective for treatment of 3A episodes as intravenous steroids.