Combined heart-liver transplantation in the MELD era: do waitlisted patients require exception status?

Combined heart-liver transplant (HLT) is a viable therapy for patients with concomitant end-stage heart and liver failure. Using data from the United Network for Organ Sharing database, we examined the cumulative incidences of transplant and mortality in waitlisted candidates for HLT, isolated heart transplant (HRT) and isolated liver transplant (LIV) in the Model for End-Stage Liver Disease era. The incidence of waitlist mortality was higher in HLT candidates than in HRT candidates (p = 0.001, 26% vs. 12% at 1 year) or LIV candidates (p = 0.005, 26% vs. 14% at 1 year). These differences persisted after stratifying by disease severity. Posttransplant survival was not significantly different between HLT and HRT recipients or between HLT and LIV recipients. In a multivariable model, undergoing HLT was associated with enhanced survival for HLT candidates (hazard ratio, 0.41; confidence interval, 0.21-0.79; p = 0.008), but undergoing HRT alone was not. Interestingly, 90% of HLT recipients were allocated an organ locally, compared to 60% of HRT candidates and 73% of LIV candidates (both p < 0.001). These data suggest that the current cardiac and liver allocation systems may underestimate the risk of death for patients with concomitant end-stage heart and liver failure on the HLT waitlist.

Heart and combined heart-kidney transplantation in patients with concomitant renal insufficiency and end-stage heart failure.

In patients with end-stage heart failure (ESHF) who are candidates for isolated heart transplant (HRT), dialysis dependence (DD) is considered an indication for combined heart-kidney transplantation (HKT). HKT remains controversial in ESHF transplant candidates with nondialysis-dependent renal insufficiency (NDDRI). Using United Network for Organ Sharing data, we examined the cumulative incidences of transplant and mortality in patients with DD and NDDRI waitlisted for HKT or HRT. In all groups, 3-month waitlist mortality was dismal: 31% and 21% for HRT- and HKT-listed patients with DD and 12% and 7% for HRT- and HKT-listed patients with NDDRI. Five-year posttransplant survival was improved in HKT recipients compared with HRT recipients for both patients with DD (73% vs. 51%, p<0.001) and NDDRI (80% vs. 69%, p<0.001). Likewise, multivariable analysis associated HKT with better outcomes than HRT in HKT-listed patients, although both improved survival. These data argue strongly for HKT in ESHF transplant candidates with DD. However, in patients with NDDRI, HKT must be weighed against the possibility of renal recovery with isolated HRT. Whether HRT (followed by a staged kidney transplant in patients who do not recover renal function after HRT), as opposed to HKT, maximizes organ benefit for patients with NDDRI and ESHF requires assessment. Nevertheless, given their dismal waitlist outcomes and excellent posttransplant results, we suggest that patients with DD and NDDRI with ESHF be considered for early listing and transplant.

Fatal cardiac and renal allograft rejection with lenalidomide therapy for light-chain amyloidosis.

We describe a patient who underwent a successful heart and kidney transplant for light-chain amyloidosis. She had an excellent hematologic response to bortezomib/dexamethasone therapy. Follow-up therapy with lenalidomide was started, and the patient quickly had a fatal allograft rejection of the heart and kidney. We present evidence to support the theory that lenalidomide, a known immunomodulator, may have stimulated the immune system and precipitated the fatal rejection episode.

Twenty-year survivors of heart transplantation at Stanford University.

Human heart transplantation started 40 years ago. Medical records of all cardiac transplants performed at Stanford were reviewed. A total of 1446 heart transplantations have been performed between January 1968 and December 2007 with an increase of 1-year survival from 43.1% to 90.2%. Sixty patients who were transplanted between 1968 and 1987 were identified who survived at least 20 years. Twenty-year survivors had a mean age at transplant of 29.4 +/- 13.6 years. Rejection-free and infection-free 1-year survivals were 14.3% and 18.8%, respectively. At their last follow-up, 86.7% of long-term survivors were treated for hypertension, 28.3% showed chronic renal dysfunction, 6.7% required hemodialysis, 10% were status postkidney transplantation, 13.3% were treated for diabetes mellitus, 36.7% had a history of malignancy and 43.3% had evidence of allograft vasculopathy. The half-life conditional on survival to 20 years was 28.1 years. Eleven patients received a second heart transplant after 11.9 +/- 8.0 years. The most common causes of death were allograft vasculopathy (56.3%) and nonlymphoid malignancy (25.0%). Twenty-year survival was achieved in 12.5% of patients transplanted before 1988. Although still associated with considerable morbidity, long-term survival is expected to occur at much higher rates in the future due to major advances in the field over the past decade.

Phase 1 human trial of adenosine-potassium cardioplegia.

BACKGROUND: The cardioprotective role of adenosine in various models of ischemia-reperfusion, including adenosine supplementation to cardioplegic formulations, has been studied extensively. The appropriate dose of adenosine in humans is uncertain and could be limited by systemic hypotension or AV block. METHODS AND RESULTS: An open-label, nonrandomized phase 1 adenosine dose-ranging study was performed. Patients scheduled for primary isolated coronary bypass surgery were eligible for the study. Antegrade warm blood potassium cardioplegia (ratio, 4:1, blood to crystalloid) was administered in the routine fashion, with adenosine added to the initial 1000-mL dose and final 500-mL dose. Patients were studied in blocks of 4 per concentration. An escalating adenosine dosage schedule was planned to produce blood cardioplegia concentrations from 0 to 250 mumol/L, and the blocks were tested sequentially. Stopping rules were defined for systemic hypotension (phenylephrine dose during cardiopulmonary bypass > or = 5.0 mg; phenylephrine dose during cardioplegic induction > or = 800 micrograms) and AV block (permanent pacemaker insertion; temporary pacing dependency for > 90 minutes after cardiopulmonary bypass). Doses of 1, 2.5, 5, 10, and 25 mumol/L were well tolerated. With 50 mumol/L, systemic hypotension occurred during cardioplegic induction in 3 of 4 patients versus 1 of 24 (P < .005) at all lower concentrations (880 +/- 217 versus 297 +/- 286 micrograms phenylephrine per patient). The studies were repeated with an 8:1 blood-to-crystalloid cardioplegia delivery system. Adenosine concentrations of 0 (n = 4), 15 (n = 12), 20 (n = 8), and 25 mumol/L (n = 4) were tested. Hypotension during cardioplegic induction was more prevalent (P = .05) with the higher doses (15 mumol/L, 394 +/- 189 micrograms, 1 of 12 patients; 20 mumol/L, 360 +/- 355 micrograms, 2 of 8 patients; 25 mumol/L, 600 +/- 478 micrograms, 2 of 4 patients). There were no differences with respect to systemic hypotension during cardiopulmonary bypass or for pacing > 90 minutes after discontinuation of cardiopulmonary bypass, and no patient required permanent pacing. There have been no deaths, Q-wave myocardial infarctions, intra-aortic balloon pump insertions, or cerebral infarctions in the total sample of 56 patients. CONCLUSIONS: Our initial investigations have shown that adenosine can be safely administered during cardiopulmonary bypass. The authors recommend that further studies are warranted using adenosine 15 to 25 mumol/L, depending on the delivery system.