Routine Surveillance Biopsies after Pediatric Heart Transplantation - Are They Still Necessary?

Abstract

Purpose Regular surveillance endo-myocardial biopsies (rsEMB) after heart transplantation (HTx) remain the standard of care to detect allograft rejection. However, in small children the procedure is highly invasive, increases hospitalization and may misdiagnose rejections. We studied efficacy and safety of a very restrictive rsEMB protocol. Methods Single center, retrospective observational study to evaluate the early follow-up of all pediatric HTx patients between 2009- 2018. Following our institutional protocol, rsEMB was performed only once, 12 months after HTx. Instead, echocardiography, ECG and routine blood samples including T-Cell count, HLA-antibodies and levels of immunosuppressants were monitored frequently. Calcineurininhibitors and Everolimus were the primary immunosuppressants, together with steroids for the first months. Results 47 patients (25 male) were transplanted at a median age of 10.1 (0.1- 17) years. Median time since HTx was 3.4 (0.1- 9.9) years. Six patients (12.8%) had a univentricular circulation prior to HTx, 15 patients (32%) were bridged with an LVAD. Overall mortality was 10.6% (n= 5). Seven patients have not yet completed the first year after HTx. 35 patients underwent their one year follow-up including an rsEMB without complications: Histology showed no acute cellular rejection (ACR) or antibody-mediated rejection (AMR) and revealed two (5.7%) mild chronic cellular rejections (CCR) without therapeutic consequences, both no longer detectable in the follow-up EMBs 3 months later. Mild cardiac allograft vasculopathy was seen in two samples (6.3%). At 1-year follow-up, there were no clinical signs of heart failure in any of the 35 patients. Echo revealed a mean LVEF of 70 (50- 78) % with normal strain and tissue Doppler values. Median serum creatinine level was 0.5 (0.2- 1.3) mg/dL, median NT-pro BNP 209 (50- 1575) pg/ml and normal ranges for Troponin T were found. No donor specific HLA- antibodies were detected. During the whole study period there were not more than seven clinically indicated, unscheduled biopsies, exposing one ACR 2R (14%) and two ACR 1R (29%). Tests for AMR, CCR and cardiac allograft vasculopathy were all negative. Conclusion Our findings suggest that rsEMB can safely be reduced in number and replaced with non-invasive methods without increasing the risk of overlooking acute allograft rejection in children. Regular surveillance endo-myocardial biopsies (rsEMB) after heart transplantation (HTx) remain the standard of care to detect allograft rejection. However, in small children the procedure is highly invasive, increases hospitalization and may misdiagnose rejections. We studied efficacy and safety of a very restrictive rsEMB protocol. Single center, retrospective observational study to evaluate the early follow-up of all pediatric HTx patients between 2009- 2018. Following our institutional protocol, rsEMB was performed only once, 12 months after HTx. Instead, echocardiography, ECG and routine blood samples including T-Cell count, HLA-antibodies and levels of immunosuppressants were monitored frequently. Calcineurininhibitors and Everolimus were the primary immunosuppressants, together with steroids for the first months. 47 patients (25 male) were transplanted at a median age of 10.1 (0.1- 17) years. Median time since HTx was 3.4 (0.1- 9.9) years. Six patients (12.8%) had a univentricular circulation prior to HTx, 15 patients (32%) were bridged with an LVAD. Overall mortality was 10.6% (n= 5). Seven patients have not yet completed the first year after HTx. 35 patients underwent their one year follow-up including an rsEMB without complications: Histology showed no acute cellular rejection (ACR) or antibody-mediated rejection (AMR) and revealed two (5.7%) mild chronic cellular rejections (CCR) without therapeutic consequences, both no longer detectable in the follow-up EMBs 3 months later. Mild cardiac allograft vasculopathy was seen in two samples (6.3%). At 1-year follow-up, there were no clinical signs of heart failure in any of the 35 patients. Echo revealed a mean LVEF of 70 (50- 78) % with normal strain and tissue Doppler values. Median serum creatinine level was 0.5 (0.2- 1.3) mg/dL, median NT-pro BNP 209 (50- 1575) pg/ml and normal ranges for Troponin T were found. No donor specific HLA- antibodies were detected. During the whole study period there were not more than seven clinically indicated, unscheduled biopsies, exposing one ACR 2R (14%) and two ACR 1R (29%). Tests for AMR, CCR and cardiac allograft vasculopathy were all negative. Our findings suggest that rsEMB can safely be reduced in number and replaced with non-invasive methods without increasing the risk of overlooking acute allograft rejection in children.