Predictors of survival to orthotopic heart transplant in patients with light chain amyloidosis

Abstract

Background Orthotopic heart transplant (OHT) followed by myeloablative chemotherapy and autologous stem cell transplant (ASCT) has been successful in the treatment of light chain (AL) cardiac amyloidosis. The purpose of this study is to identify predictors of survival to OHT in patients with end stage heart failure due to AL amyloidosis, and compare post-OHT survival of cardiac amyloid patients to that of other cardiomyopathy patients undergoing OHT. Methods From January 2000 to June 2011, 31 patients with end stage heart failure secondary to AL amyloidosis were listed for OHT at Massachusetts General Hospital (MGH). Univariate and multivariate regression analyses identified predictors of survival to OHT. Kaplan-Meier analysis compared survival between MGH amyloidosis patients and the Scientific Registry of Transplant Recipients (SRTR) non-amyloid cardiomyopathy patients. Results Low body mass index (BMI) was the only predictor of survival to OHT in patients with end stage heart failure due to cardiac amyloidosis. Survival of cardiac amyloid patients who died prior to receiving a donor heart was only 63 ± 45 days after listing. Patients who survived to OHT received a donor organ at 53 ± 48 days after listing. Survival of AL amyloidosis patients on the waitlist was less than patients waitlisted for all other non-amyloid diagnoses. The long-term survival of transplanted amyloid patients was no different than the survival of non-amyloid, restrictive (p=0.34), non-amyloid dilated (p=0.34) or all non-amyloid cardiomyopathy patients (p=0.22) in the SRTR database. Conclusions Those that survive to OHT followed by ASCT have a survival rate similar to other cardiomyopathy patients undergoing OHT. However, more than one third of the patients died awaiting OHT. The only predictor of survival to OHT in AL amyloidosis patients was low BMI, which correlated with shorter waitlist time. To optimize the survival of these patients, access to donor organs must be improved. In light chain (AL) amyloidosis, amyloid fibrils derived from clonal lambda or kappa immunoglobulin light chains deposit abnormally in organs. Cardiac involvement is apparent echocardiographically in 60% of AL amyloidosis patients at the time of diagnosis, with clinical evidence of heart failure in 69% of patients.1 The median survival of AL amyloidosis patients presenting with any heart failure symptom is 8.5 months2 and even less for end-stage heart failure pateints.

Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience

“…Recent reports suggest improved short term outcomes with advances in chemotherapy and AHSCT, with the Stanford series reporting 1 year survival of 100% [20] . In the MGH series of 18 AL patients undergoing OHT approximately 60% of patients were alive at 6 years [10] , and, in contrast to earlier studies [8,9,21] , was similar to that of nonamyloid patients. Although overall survival in our study was reduced compared with patients transplanted for nonamyloid indications, our series includes many early era patients who did not receive the benefit of current therapy for amyloidosis.…”

“…Time is of the essence in these patients. In our experience and others, approximately 40% of AL patients listed do not undergo OHT either due to death or deterioration [10] . This seems to be related to both delayed diagnosis, as well as inability to support these patients with traditional heart failure therapy and devices.…”

“…Perhaps cardiac biomarkers like ST2 may lend insight to those with irreparable damage despite effective chemotherapy [26] . "Better selection" also means choosing those patients in whom the underlying plasma cell clone can be controlled, since in our study and others effective chemotherapy has resulted in the best outcomes post OHT [10,16,20] . Most of the patients in our series did not receive chemotherapy prior to OHT because the only chemotherapies available at the time of their diagnosis were oral melphalan and prednisone and high dose melphalan with AHSCT.…”

“…This seems to be related to both delayed diagnosis, as well as inability to support these patients with traditional heart failure therapy and devices. In the MGH series, patients with amyloidosis had a mortality hazard ratio of 4.7 (95%CI: 2.8, 11.8) as compared to nonamyloidosis patients while on the waiting list [10] . The only predictive factor of survival to OHT in that study was BMI patients with lower BMI fared better than those with higher BMI, although this was not confirmed in our study.…”

“…Orthotopic heart transplantation (OHT) in AL has been limited due to the risk of disease progression in other organs and recurrence of amyloid deposition in the transplanted heart [7,8] . Although earlier studies suggested inferior outcomes of OHT for compared with nonamyloid indications [8,9] , more recent reports have found survival similar to other forms of heart failure [10] . Controversy regarding the role of OHT in AL remains [11,12] and many centers consider amyloidosis to be a contraindication to OHT.…”