Disparities in donor heart acceptance between the USA and Europe: clinical implications.

BACKGROUND AND AIMS: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. METHODS: Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. RESULTS: Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. CONCLUSIONS: Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.

Severe gastroparesis after orthotopic heart transplantation.

We present a case of severe gastroparesis in a recipient of orthotopic heart transplantation. Although a rare condition after heart transplantation, it is a potential cause of significant morbidity, including vomiting, aspiration and pneumonia. Moreover, impaired gastric emptying alters the pharmacokinetics of immunosuppressive medication with increased risk of severe side effects. Herein, we describe a diagnostic and therapeutic strategy that was successfully applied in a patient with gastroparesis.

Impact of Rabbit Antithymocyte Globulin Dose on Long-term Outcomes in Heart Transplant Patients.

BACKGROUND: Optimal dosing strategies have not been established for rabbit antithymocyte globulin (rATG) after heart transplantation, and there is currently wide variability in rATG regimens with respect to both dose and duration. METHODS: In a retrospective, single-center analysis, 523 patients undergoing heart transplantation during 1996 to 2009 were stratified by cumulative rATG dose: less than 4.5 mg/kg (group A), 4.5 to 7.5 mg/kg (group B) or greater than 7.5 mg/kg (group C). RESULTS: Survival at 1 year after transplantation was 80% in group A, 90% in group B, and 88% in group C (P = 0.062). Incidence of acute rejection per 1000 patient-years was significantly higher in group A (hazards ratio [HR], 54.8; 95% confidence interval [95% CI], 33.9-83.8) compared to groups B (19.6; 95% CI, 11.4-31.4) and C (23.6; 95% CI, 17.5-31.3). Incidence of severe infection 10 years after transplantation was higher in group C (45%) than groups A (37%) or B (23%) (P < 0.001); cytomegalovirus infection rates were 35%, 20% and 23%, respectively (P = 0.009). Multivariable Cox regression showed an HR of 0.51 (95% CI, 0.25-1.02) for acute rejection with group B versus group A, and 0.54 (95% CI, 0.33-0.88; P = 0.013) for severe infection. The rate of malignancy per 1000 patient-years was higher in groups B (13.85) and C (14.95) than group A (7.83). CONCLUSIONS: These retrospective data suggest that a cumulative rATG dose of 4.5 to 7.5 mg/kg may offer a better risk-benefit ratio than lower or higher doses, with acceptable rates of infection and posttransplant malignancy. Prospective trials are needed.

The Seville expert workshop for progress in posttransplant lymphoproliferative disorders.

: Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein-Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD.

Safety and efficacy of statin therapy in patients switched from cyclosporine a to sirolimus after cardiac transplantation.

INTRODUCTION: Statins are an established therapy after cardiac transplantation. Sirolimus (Srl) has been used successfully in cardiac transplant patients. However, potential side effects are hyperlipidemia and interactions with statins. The aim of the study was to evaluate the safety and efficacy of statin therapy after switch to a Srl-based immunosuppression. PATIENTS AND METHODS: Ninety-eight long-term patients were switched from Cyclosporine A to Srl. Also all patients received mycophenolate mofetil alone or mycophenolate mofetil plus steroid therapy. Reasons for switch were renal dysfunction, graftvasculopathy, or skin cancer. Patients were switched 7.8+/-4.7 years after transplant. Total observation period was 12 months before and after switch, respectively. Safety evaluation consisted of regular measurements of CPK and liver enzymes to evaluate the incidence myopathy and hepatoxicity. Efficacy analysis was performed by serial blood lipid assessments (low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides). RESULTS: Forty-three percentage of patients received atorvastatin, 38% pravastatin, and 18% other drugs or therapy changes. Most lipid blood levels increased significantly after switch (cholesterol: 192.9+/-38.6 mg/dL vs. 221.8+/-49.2 mg/dL, P<0.0001; low-density lipoprotein: 108.0+/-35.6 mg/dL vs. 123.8+/-37.9 mg/dL, P<0.0001; and triglycerides: 178.3+/-88.2 mg/dL vs. 225.5+/-139.1 mg/dL, P<0.0001). Blood lipid levels after switch were not associated with statin type. Overall safety was acceptable, although incidence of myopathy doubled after switch (n=20 vs. 40; P<0.01). However, most cases were asymptomatic CPK elevations in the pravastatin group. Hepatotoxicity rate was 4% and only temporary. CONCLUSION: Statin therapy after switch from cyclosporine A to Srl in long-term cardiac transplant patients is safe. However, regular testing of blood lipids and CPK should be mandatory.

Effect of mycophenolate mofetil therapy on lymphocyte activation in heart transplant recipients.

BACKGROUND: Mycophenolic acid is reported to provide effective immunosuppression by inhibiting inosine monophosphate dehydrogenase. In an attempt to monitor the effects of therapy with mycophenolate mofetil, we measured the expression of the activation markers CD25, CD38, CD69 and HLA-DR on lymphocytes of patients after heart transplantation. METHODS: Thirty-six patients enrolled in the study were randomly assigned to one of two groups. Patients in the control group (n = 15) received cyclosporine, azathioprine and prednisone. Patients in the study group (n = 21) were switched from azathioprine to mycophenolate mofetil (MMF) 3 months after heart transplantation. The expressions of the activation markers CD25, CD38, CD69 and HLA-DR on B cells, T cells and natural killer (NK) cells in peripheral blood were determined by flow cytometry. RESULTS: In patients treated with MMF a significant reduction of the B-cell count was observed in comparison to a healthy control group and patients under therapy with azathioprine. The decline of B cells in the MMF group started 3 months after onset of therapy and, after 1 year, was nearly halved. In addition, the percentages of CD38-positive B cells, activated T cells (CD4(+)/CD25(+), CD8(+)/CD38(+)) and HLA-DR-expressing NK cells were reduced during therapy with MMF. CONCLUSIONS: Our studies have shown administration of MMF to be associated with a reduction of B lymphocytes and a downregulation of activation markers on B cells. In contrast to in vitro findings, our data indicate that the immunosuppressive effect of MMF in vivo is exhibited mainly on B cells.