Background. Although orthotopic liver transplantation (OLT) and combined heart and liver transplantation (CHLT) are accepted therapeutic strategies in ATTR, Centers with an unrestricted access to both facilities are few and long term results are poorly defined. We report results of our transplantation strategy: OLT in symptomatic stage I neuropathy with no or mild heart involvement, CHLT in non-Val30Met stage I neuropathy and severe cardiomyopathy (mean left ventricular wall thickness >14 mm), even in absence of heart failure. Methods. Between 1993 and December 2012, 47 patients underwent organ transplantation (34 OLT and 13 CHLT) and were evaluated for survival and incremental risk factors for mortality. Results. 31 patients were males (66%) with median age of 47 years (range 22-68). Val30Met patients were 15 (32%) and all underwent OLT; the most frequent non-Val30Met mutations were Glu89Gln (n=9, 19%) and Thr49Ala (n=6, 13%). During a median follow-up of 5 years (range 0-20), 19 (40%) patients died (16 OLT, 3 CHLT). Neurologic progression was the cause of death in 6 patients (5 in OLT and 1 CHLT subgroups), severe heart failure in 3 OLT. One-year survival was 77% (71% in OLT and 92% in CHLT). Survival at 5 years was 58% (54% in OLT and 68% in CHLT groups). Cox analysis identified the following independent variables associated with overall mortality: peripheral neuropathy (P=0.03), coexistence of orthostatic hypotension and gastrointestinal symptoms (P=0.02), compromised nutritional status (P=0.03) and long waiting time in list (P=0.04). Conclusions. CHLT improves mid term survival in patients with non-Val30Met mutations, mild neuropathy and definite cardiomyopathy, including those without hemodynamic impairment. However, both OLT and CHLT are suboptimal therapeutical solutions in ATTR since long term efficacy is hampered by disease progression in at least 40% of cases. Pharmacologic strategies against post-transplant wild type transthyretin deposition are needed.

Organ Transplantation strategies in Hereditary Transthyretin Amyloidosis (ATTR): long-term experience at a single Center with combined heart and liver transplant facilities

MASTROROBERTO, MARIANNA;ERCOLANI, GIORGIO;BERARDI, SONIA;LONGHI, SIMONE;SAMA, CLAUDIA;RAPEZZI, CLAUDIO;PINNA, ANTONIO DANIELE
2013

Abstract

Background. Although orthotopic liver transplantation (OLT) and combined heart and liver transplantation (CHLT) are accepted therapeutic strategies in ATTR, Centers with an unrestricted access to both facilities are few and long term results are poorly defined. We report results of our transplantation strategy: OLT in symptomatic stage I neuropathy with no or mild heart involvement, CHLT in non-Val30Met stage I neuropathy and severe cardiomyopathy (mean left ventricular wall thickness >14 mm), even in absence of heart failure. Methods. Between 1993 and December 2012, 47 patients underwent organ transplantation (34 OLT and 13 CHLT) and were evaluated for survival and incremental risk factors for mortality. Results. 31 patients were males (66%) with median age of 47 years (range 22-68). Val30Met patients were 15 (32%) and all underwent OLT; the most frequent non-Val30Met mutations were Glu89Gln (n=9, 19%) and Thr49Ala (n=6, 13%). During a median follow-up of 5 years (range 0-20), 19 (40%) patients died (16 OLT, 3 CHLT). Neurologic progression was the cause of death in 6 patients (5 in OLT and 1 CHLT subgroups), severe heart failure in 3 OLT. One-year survival was 77% (71% in OLT and 92% in CHLT). Survival at 5 years was 58% (54% in OLT and 68% in CHLT groups). Cox analysis identified the following independent variables associated with overall mortality: peripheral neuropathy (P=0.03), coexistence of orthostatic hypotension and gastrointestinal symptoms (P=0.02), compromised nutritional status (P=0.03) and long waiting time in list (P=0.04). Conclusions. CHLT improves mid term survival in patients with non-Val30Met mutations, mild neuropathy and definite cardiomyopathy, including those without hemodynamic impairment. However, both OLT and CHLT are suboptimal therapeutical solutions in ATTR since long term efficacy is hampered by disease progression in at least 40% of cases. Pharmacologic strategies against post-transplant wild type transthyretin deposition are needed.
IX International Symposium on Familial Amyloidotic Polyneuropathy (ISFAP) and the VIII International Symposium on Liver Transplantation in Familial Amyloidotic Polyneuropathy
M. Mastroroberto; G. Ercolani; E. Pilato; S. Berardi; S. Longhi; C Sama; C Rapezzi; AD Pinna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/599427
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