title: Cardiac Dysautonomia Predicts Long-Term Survival in Hereditary Transthyretin Amyloidosis After Liver Transplantation.
abstract: This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver transplantation (LT).
  
  
  
  mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it.
  
  
  
  In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability,123-meta-iodobenzylguanidine heart/mediastinum (123-MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA).
  
  
  
  Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score,123-MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The123-MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either123-MIBG H/M ratio (SMIBG) or HRRA (Satropine). AUC of SMIBGand Satropinewere greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of SMIBG, Satropine, and a reference clinical model (AUC: 0.785) were similar.
  
  
  
  Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia,123-MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome.
authors.affiliation: Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France; French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France. Electronic address: vincent.algalarrondo@u-psud.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Algalarrondo
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Hepato-Biliary Center, Paul Brousse Hospital, AP-HP, UMR-S 785, University of Paris-Sud, Villejuif, France.
authors.forename: Teresa
authors.initials: T
authors.lastname: Antonini
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Filière Neuromusculaire, Neurology Department, Kremlin Bicêtre Hospital, AP-HP, Bicêtre, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Théaudin
authors.affiliation: Physiology Department, EA4533, University of Paris-Sud, Le Kremlin Bicêtre, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Chemla
authors.affiliation: School of Pharmacy, University of Paris-Sud, Chatenay Malabry, France.
authors.forename: Anouar
authors.initials: A
authors.lastname: Benmalek
authors.affiliation: Filière Neuromusculaire, Neurology Department, Kremlin Bicêtre Hospital, AP-HP, Bicêtre, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacroix
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Hepato-Biliary Center, Paul Brousse Hospital, AP-HP, UMR-S 785, University of Paris-Sud, Villejuif, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Filière Neuromusculaire, Neurology Department, Kremlin Bicêtre Hospital, AP-HP, Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Cauquil
authors.affiliation: Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France; French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dinanian
authors.affiliation: Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France; French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Eliahou
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Hepato-Biliary Center, Paul Brousse Hospital, AP-HP, UMR-S 785, University of Paris-Sud, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France; Filière Neuromusculaire, Neurology Department, Kremlin Bicêtre Hospital, AP-HP, Bicêtre, France.
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.affiliation: Nuclear Medicine Department and Département Hospitalo Universitaire Fibrose Inflammation et Remodelage en pathologies cardiovasculaires, Bichat Claude Bernard Hospital, AP-HP, University of Paris VII, UMR-S 1148, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Guludec
authors.affiliation: Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France; French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies, Bicêtre, France.
authors.forename: Michel S
authors.initials: MS
authors.lastname: Slama
authors.affiliation: Nuclear Medicine Department and Département Hospitalo Universitaire Fibrose Inflammation et Remodelage en pathologies cardiovasculaires, Bichat Claude Bernard Hospital, AP-HP, University of Paris VII, UMR-S 1148, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Rouzet
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage*; D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D019540:Area Under Curve; D001285:Atropine / Q000008:administration & dosage; D001341:Autonomic Nervous System / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D003935:Diagnostic Techniques, Cardiovascular; D005260:Female; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000294:innervation*; D006331:Heart Diseases / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D015999:Multivariate Analysis; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009154:Mutation; D009460:Neurologic Examination; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics; D011237:Predictive Value of Tests; D054969:Primary Dysautonomias / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D016016:Proportional Hazards Models; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D018727:Muscarinic Antagonists; D011228:Prealbumin; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D001285:Atropine
keywords: cardiac amyloidosis; cardiac dysautonomia; cardiac imaging; liver transplantation; transthyretin