Acute Cellular Rejection at Long-Term Follow-Up After Heart Transplantation: A Single Center Experience in Japan

Abstract

<h3>Purpose</h3> Acute cellular rejection (ACR) is a major cause of death within 1-3 years after heart transplantation (HTx). However, recipients are usually asymptomatic in the early stages of ACR, and it is difficult to obtain specific findings of ACR using non-invasive tests. Therefore, regular endomyocardial biopsy plays an important role in monitoring for ACR. Although mortality from ACR decreases in the long term after HTx, there is no strong evidence of screening methods such as the appropriate frequency of biopsies. We retrospectively analyzed the outcome of ACR in our institution. <h3>Methods</h3> We enrolled 136 patients who underwent HTx at our hospital from May 1999 to April 2020. 7 Recipients under the age of 18 at the time of HTx were excluded. The current myocardial biopsy schedule is 1,2,3,5,7,11 weeks, 4.5,6,9 months, twice a year from 1 to 2 years, and once a year until 10 years after HTx. After that, it is once every two years. Tacrolimus (cyclosporine before 2005), mycophenolate mofetil, and prednisolone were used as first immunosuppressive therapies. Basiliximab was administered in patients with impaired renal function, elderly patients, and anti-donor antibody-positive patients. <h3>Results</h3> 129 HTx recipients (74% male, age at transplantation 41.8 ± 12.9 years) were analyzed. Grade 2R or higher grade of ACR were observed in 19 times in 13 patients during a mean follow-up period of 7.4 ± 5.0 years. Only one case with Grade 2R (3.5 years after HTx) combined with antibody-mediated rejection developed heart failure. All recipients with ACR recovered with steroid pulse therapy, and no deaths due to ACR were observed. The frequency of ACR of Grade 2R or higher in less than 1 year, 1-3 years, 3-5 years, 5-10 years, and 10 years or more after HTx was 4.0, 2.1, 2.2, 0.7, and 0 %/patients/years, respectively. The incidence of ACR was significantly higher in 15 patients who took cyclosporine as the first calcineurin inhibitor after HTx than in 114 patients who took tacrolimus (40% vs 6.1%, p <0.05). Late recurrence of ACR after HTx was seen in a patient with poor medication adherence and in a patient after immunosuppressive drug changes. <h3>Conclusion</h3> The frequency of developing ACR decreased over the years after HTx. Careful observation is still required in cases with a high risk of recurrence, such as inadequate medication adherence even long after HTx.