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Since the restart of HTx, recipients have been expected to be disciplined, avoiding all behaviors that increase the risk of rejection, so that transplant medicine will never again be criticized. Vaccination is a mainstay of the global strategy to control the COVID-19 pandemic and rebuild vibrant daily lives and economies. How to preserve information equity for COVID-19 vaccination among severely immunocompromised populations: Challenges among heart transplant recipients in Japan. [Extracted from the article]

Background: This study reports the 36-month results of a randomized, double-blind, active-controlled trial of mycophenolate mofetil (MMF) vs azathioprine (AZA) in heart transplant patients. Methods: Patients were randomized at the time of transplant to receive MMF (1,500 mg twice a day, N = 327) or AZA (1.5 to 3 mg/kg in 4 daily doses, N = 323) in addition to cyclosporine and corticosteroids; 289 patients in each group received study drug. Data were analyzed in all randomized patients (enrolled) and in patients who received study medications (treated). Clinical and graft assessments continued for 36 months. Results: For the co-primary end-point, 53 of 289 (18.3%) AZA-treated patients either died or received another transplant compared with 34 of 289 (11.8%) MMF-treated patients (p < 0.01). Time to re-transplantation or patient death was significantly shorter for AZA- than MMF-treated patients (p = 0.029). In patients undergoing intravascular ultrasound, the change in mean maximal intimal thickness was less for the MMF group than for the AZA group (0.06 ± 0.03 mm vs 0.13 ± 0.03 mm, respectively; p = 0.056). No significant differences between treatments were observed in quantitative coronary angiographic measurements of transplant coronary vasculopathy. Congestive heart failure, atrial arrhythmia and leukopenia were more common in the AZA group, whereas diarrhea, esophagitis, Herpes simplex, Herpes zoster and cytomegalovirus (CMV) tissue invasion were more common in MMF-treated patients. Conclusion: MMF reduces mortality and graft loss up to 36 months after transplantation. [Copyright &y& Elsevier]

Background: Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival.Methods: We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002. Fifty-six patients who had received donor hearts at least 50 years of age were compared with 611 recipients of donor hearts less than 50 years of age. Clinicopathologic parameters were analyzed for their effect on mortality using the Cox proportional hazard model with calculation of hazard ratios (HR). Cut-point analysis of donor age was used to determine which donor age is associated with the greatest risk of mortality after transplant.Results: Recipients of donor hearts at least 50 years of age were older (58.5 years ± 7.0 vs 53.2 ± 11.6; mean ± standard deviation [SD]; p < 0.0001), suffered more often from ischemic cardiomyopathy (69% vs 50%, p = 0.01), and experienced a longer waiting time (192.2 days ± 301.0 vs 138.6 ± 190.8, p < 0.0001). Donor hearts at least 50 years of age (age 54.1 ± 3.5 years) were more often female (50% vs 34%, p = 0.03), died less often of “head trauma” (9% vs 42%, p < 0.0001), and exhibited fewer cytomegalovirus (CMV) mismatches (29% vs 39%, p = 0.04) than donor hearts less than 50 years of age (age 26.8 ± 12.3 years). Multivariate predictors of mortality were rejection index (HR 1.90 per unit [rejections/100 survival days], p < 0.0001), donor age (HR 1.16 per 10-year increment, p = 0.002), and recipient age (HR 1.24 per 10-year increment, p = 0.04). Recipients of donor hearts at least 50 years of age had reduced 1-year and 5-year survival ([65.7% vs 81.7%, p < 0.05] and [48.3% vs 68.4%, p < 0.05], respectively), as well as a higher proportion of deaths occurring within 1 month of transplant (41% of total deaths vs 23%, p = 0.06). Cut-point analysis indicated the characteristic of donor age of at least 40 years (categorical variable) to predict mortality with the same degree of fit as age used as a continuous variable.Conclusions: Although we observed a substantial reduction in survival among patients who were allocated donor hearts at least 50 years of age, this difference was not solely attributable to the categorical variable of donor age 50 in this group. Donor age as a continuous variable, however, was determined to be a notable predictor of survival and use of the donor age cut-point of 40 years (categorical variable) allowed risk stratification with similar accuracy. The use of a donor age cut-point of 40 years may be a useful clinical criterion for graft-related risk assessment. [Copyright &y& Elsevier]

The article discusses the shortage of organ donor used in cardiac transplantation therapy for patients with advanced heart failure. Topics include the use of older donor hearts, the utilization of mechanical circulatory support (MCS), and the myocardial revascularization. Outcomes for older donor heart transplantation is mentioned.

Background: Everolimus, a novel proliferation inhibitor and immunosuppressive agent, may suppress cardiac-allograft vasculopathy. We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant. Methods: A total of 634 patients were randomly assigned to receive 1.5 mg of everolimus per day (209 patients), 3.0 mg of everolimus per day (211 patients), or 1.0 to 3.0 mg of azathioprine per kilogram of body weight per day (214 patients), in combination with cyclosporine, corticosteroids, and statins. The primary efficacy end point was a composite of death, graft loss or retransplantation, loss to follow-up, biopsy-proved acute rejection of grade 3A, or rejection with hemodynamic compromise. Results: At six months, the percentage of patients who had reached the primary efficacy end point was significantly smaller in the group given 3.0 mg of everolimus (27.0 percent, P<0.001) and the group given 1.5 mg of everolimus (36.4 percent, P=0.03) than in the azathioprine group (46.7 percent). Intravascular ultrasonography showed that the average increase in maximal intimal thickness 12 months after transplantation was significantly smaller in the two everolimus groups than in the azathioprine group. The incidence of vasculopathy was also significantly lower in the 1.5-mg group (35.7 percent, P=0.045) and the 3.0-mg group (30.4 percent, P=0.01) than in the azathioprine group (52.8 percent). The rates of cytomegalovirus infection were significantly lower in the 1.5-mg group (7.7 percent, P<0.001) and the 3.0-mg group (7.6 percent, P<0.001) than in the azathioprine group (21.5 percent). Rates of bacterial infection were significantly higher in the 3.0-mg group than in the azathioprine group. Serum creatinine levels were also significantly higher in the two everolimus groups than in the azathioprine group. Conclusions: Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem. N Engl J Med 2003;349:847-58. [ABSTRACT FROM AUTHOR]

Background: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced formulation that delays the release of mycophenolic acid (MPA). Its efficacy and safety has been proven in several clinical trials in renal transplantation. Methods: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1,080 mg twice daily or mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men or women aged 18 to 65 years, undergoing primary heart transplantation, who were treated with cyclosporine microemulsion and corticosteroids as basic immunosuppression. The primary study objective was to investigate the incidence of biopsy-proven and treated acute rejection, graft loss or death (defined as treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de novo heart transplant recipients. Secondary objectives included assessment of the overall safety and tolerability of EC-MPS vs MMF in the study population. Results: The primary efficacy variable, treatment failure at 6 months, was similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95% confidence interval [CI]: −21.0% to 10.4%). At 12 months, treatment failure was 57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: −18.4 to 12.7), and death and graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2-sided 95% CI: −12.2 to 4.1). The overall safety profile was similar for both groups. Significantly more patients on MMF had two or more study medication dose reductions during the treatment period. Conclusions: These 6- and 12-month results show that EC-MPS is therapeutically similar to MMF in de novo heart transplant recipients and has a comparable safety profile. [Copyright &y& Elsevier]

Background: Listing status for heart transplantation (Tx) patients was changed in 1999 from Status 1 and 2 to Status 1A, 1B and 2. Because the selection process was modified in favor of seriously ill patients, it was not clear whether this change would affect survival or other aspects of transplant management. Methods: We examined outcomes in 551 patients transplanted at our institution between 1986 and 2002 (pre-1999: n = 419; post-1999: n = 132) to determine the effects of change in listing protocol on transplant outcome. Results: Using Cox proportional hazard analysis, survival was not different between pre-1999 (pre) and post-1999 (post). Overall waiting-list times were longer post-1999 (pre: 134 ± 10.5 days, post: 172 ± 15.6 days; p = 0.044), and were longer post-1999 for blood groups A (177 vs 123 days), B (96 vs 84 days) and O (229 vs 172 days), but were shorter post for blood group AB (42 vs 68 days). Survival was not affected by age (pre: 53.7 ± 0.52 years, post: 53.1 ± 1.04 years; hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.996 to 1.023; p = 0.181), male gender (HR 1.132; 95% CI 0.822 to 1.56; p = 0.447) or waiting-list time. Serum creatinine was similar between the 2 groups (pre: 1.25 ± 0.02, post: 1.26 ± 0.04; p = 0.794), whereas pulmonary artery (PA) diastolic pressure was increased post-1999 (pre: 24.9 ± 0.46, post: 27.0 ± 0.74; p = 0.023). Survival was not affected by PA pressure (HR 1.00; 95% CI 0.986 to 1.014; p = 0.976), but an elevated pre-transplant creatinine reduced survival (HR 1.484; 95% CI 1.139 to 1.933; p = 0.003). Conclusions: The change in listing status implemented in 1999 caused an increase in wait times for patients with blood types A, B and O, and shortened wait time for type AB; however, no differences occurred in overall post-transplant survival after the change in listing protocol. Age, gender and PA pressure had no effect on survival in either time period, whereas pre-transplant serum creatinine decreased survival in both patient groups. [Copyright &y& Elsevier]