Cardiac Transplantation in Danon Disease

Abstract

PurposeDanon disease is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene. Currently, there are no disease modifying therapies for Danon disease. The purpose of this study is to characterize individuals with Danon disease who undergo cardiac transplantation and describe their outcomes.MethodsRetrospective data of individuals with Danon disease who underwent cardiac transplantation (N=16) were obtained from 6 centers. Post-transplantation outcomes included survival, re-transplantation, and episodes of acute rejection within the first year. Analysis of preoperative patient characteristics was stratified by sex. Because the study was not limited to adults, z-scores were calculated for echocardiographic parameters to allow for comparisons between groups.ResultsMedian follow up time in this dataset was 2.35 years (IQR: 0.8 years - 8.3 years). Males had higher preoperative AST and ALT (p=0.02) compared to females and were more likely than females to have muscular symptoms (p=0.037). From a cardiac perspective, pre-transplant EF was lower in females compared to males (p=0.047), while left ventricular hypertrophy was more prominent in males compared to females (p<0.001). [TABLE] There was 1 death (female) in the entire cohort (occurred 5 days post-transplant) and no re-transplants. At 1 year, there were no episodes of antibody mediated rejection, and 5 episodes of acute cellular rejection (33%) in those who survived to discharge after transplantation.ConclusionDanon disease is a progressive multisystem disease. Understanding the individuals who undergo cardiac transplantation and their outcomes is critical for informing patient selection and guiding decisions regarding organ allocation. Short term post-transplant outcomes are acceptable in Danon disease and suggest that cardiac transplantation is a treatment option for these patients. Danon disease is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene. Currently, there are no disease modifying therapies for Danon disease. The purpose of this study is to characterize individuals with Danon disease who undergo cardiac transplantation and describe their outcomes. Retrospective data of individuals with Danon disease who underwent cardiac transplantation (N=16) were obtained from 6 centers. Post-transplantation outcomes included survival, re-transplantation, and episodes of acute rejection within the first year. Analysis of preoperative patient characteristics was stratified by sex. Because the study was not limited to adults, z-scores were calculated for echocardiographic parameters to allow for comparisons between groups. Median follow up time in this dataset was 2.35 years (IQR: 0.8 years - 8.3 years). Males had higher preoperative AST and ALT (p=0.02) compared to females and were more likely than females to have muscular symptoms (p=0.037). From a cardiac perspective, pre-transplant EF was lower in females compared to males (p=0.047), while left ventricular hypertrophy was more prominent in males compared to females (p<0.001). [TABLE] There was 1 death (female) in the entire cohort (occurred 5 days post-transplant) and no re-transplants. At 1 year, there were no episodes of antibody mediated rejection, and 5 episodes of acute cellular rejection (33%) in those who survived to discharge after transplantation. Danon disease is a progressive multisystem disease. Understanding the individuals who undergo cardiac transplantation and their outcomes is critical for informing patient selection and guiding decisions regarding organ allocation. Short term post-transplant outcomes are acceptable in Danon disease and suggest that cardiac transplantation is a treatment option for these patients.