Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis

Background For the time being, tafamidis is the only approved treatment for wild‐type transthyretin cardiac amyloidosis. However, benefits on all‐cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death wit...

Full description

Saved in:
Bibliographic Details
Main Authors: Paolo Milani, Giuseppe Damiano Sanna, Roberta Mussinelli, Marco Basset, Gianluigi Guida, Andrea Attanasio, Martina Nanci, Francesca Fabris, Claudia Bellofiore, Alessandro Fogliani, Elisa Novello, Francesca Benigna, Laura Obici, Pietro Benvenuti, Martina Ciardo, Mario Nuvolone, Manuela Averaimo, Gavino Casu, Andrea Foli, Stefano Perlini, Giampaolo Merlini, Giovanni Palladini
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.036755
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850233801158950912
author Paolo Milani
Giuseppe Damiano Sanna
Roberta Mussinelli
Marco Basset
Gianluigi Guida
Andrea Attanasio
Martina Nanci
Francesca Fabris
Claudia Bellofiore
Alessandro Fogliani
Elisa Novello
Francesca Benigna
Laura Obici
Pietro Benvenuti
Martina Ciardo
Mario Nuvolone
Manuela Averaimo
Gavino Casu
Andrea Foli
Stefano Perlini
Giampaolo Merlini
Giovanni Palladini
author_facet Paolo Milani
Giuseppe Damiano Sanna
Roberta Mussinelli
Marco Basset
Gianluigi Guida
Andrea Attanasio
Martina Nanci
Francesca Fabris
Claudia Bellofiore
Alessandro Fogliani
Elisa Novello
Francesca Benigna
Laura Obici
Pietro Benvenuti
Martina Ciardo
Mario Nuvolone
Manuela Averaimo
Gavino Casu
Andrea Foli
Stefano Perlini
Giampaolo Merlini
Giovanni Palladini
author_sort Paolo Milani
collection DOAJ
description Background For the time being, tafamidis is the only approved treatment for wild‐type transthyretin cardiac amyloidosis. However, benefits on all‐cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months. Methods and Results We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group–Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild‐type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow‐up was 43 months, and 367 patients (53%) died. Eighteen‐month death was predicted by NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group–Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard‐ and high‐risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (P<0.001). This was confirmed in the validation set. Conclusions A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group–Performance Status identifies subjects with cardiac wild‐type transthyretin cardiac amyloidosis at high risk of early death.
format Article
id doaj-art-73a8bda1733c4eb59abafb9446535c36
institution OA Journals
issn 2047-9980
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj-art-73a8bda1733c4eb59abafb9446535c362025-08-20T02:02:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-01-0114110.1161/JAHA.124.036755Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac AmyloidosisPaolo Milani0Giuseppe Damiano Sanna1Roberta Mussinelli2Marco Basset3Gianluigi Guida4Andrea Attanasio5Martina Nanci6Francesca Fabris7Claudia Bellofiore8Alessandro Fogliani9Elisa Novello10Francesca Benigna11Laura Obici12Pietro Benvenuti13Martina Ciardo14Mario Nuvolone15Manuela Averaimo16Gavino Casu17Andrea Foli18Stefano Perlini19Giampaolo Merlini20Giovanni Palladini21Department of Molecular Medicine University of Pavia ItalyDepartment of Molecular Medicine University of Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyCardiology Universitary Department IRCCS Policlinico San Donato San Donato Milanese ItalyCardiology Universitary Department IRCCS Policlinico San Donato San Donato Milanese ItalyDepartment of Molecular Medicine University of Pavia ItalyInstitute of Cardiology, Maggiore Hospital Crema ItalyDepartment of Molecular Medicine University of Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyDepartment of Molecular Medicine University of Pavia ItalyDepartment of Molecular Medicine University of Pavia ItalyCardiocentro Bellinzona ItalyClinical and Interventional Cardiology Sassari University Hospital Sassari ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyAmyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia ItalyDepartment of Molecular Medicine University of Pavia ItalyDepartment of Molecular Medicine University of Pavia ItalyBackground For the time being, tafamidis is the only approved treatment for wild‐type transthyretin cardiac amyloidosis. However, benefits on all‐cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months. Methods and Results We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group–Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild‐type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow‐up was 43 months, and 367 patients (53%) died. Eighteen‐month death was predicted by NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group–Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard‐ and high‐risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (P<0.001). This was confirmed in the validation set. Conclusions A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group–Performance Status identifies subjects with cardiac wild‐type transthyretin cardiac amyloidosis at high risk of early death.https://www.ahajournals.org/doi/10.1161/JAHA.124.036755amyloidosisbiomarkersprognosisstaging
spellingShingle Paolo Milani
Giuseppe Damiano Sanna
Roberta Mussinelli
Marco Basset
Gianluigi Guida
Andrea Attanasio
Martina Nanci
Francesca Fabris
Claudia Bellofiore
Alessandro Fogliani
Elisa Novello
Francesca Benigna
Laura Obici
Pietro Benvenuti
Martina Ciardo
Mario Nuvolone
Manuela Averaimo
Gavino Casu
Andrea Foli
Stefano Perlini
Giampaolo Merlini
Giovanni Palladini
Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
amyloidosis
biomarkers
prognosis
staging
title Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
title_full Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
title_fullStr Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
title_full_unstemmed Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
title_short Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
title_sort predictors of early death in patients with wild type transthyretin cardiac amyloidosis
topic amyloidosis
biomarkers
prognosis
staging
url https://www.ahajournals.org/doi/10.1161/JAHA.124.036755
work_keys_str_mv AT paolomilani predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT giuseppedamianosanna predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT robertamussinelli predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT marcobasset predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT gianluigiguida predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT andreaattanasio predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT martinananci predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT francescafabris predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT claudiabellofiore predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT alessandrofogliani predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT elisanovello predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT francescabenigna predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT lauraobici predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT pietrobenvenuti predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT martinaciardo predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT marionuvolone predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT manuelaaveraimo predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT gavinocasu predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT andreafoli predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT stefanoperlini predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT giampaolomerlini predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis
AT giovannipalladini predictorsofearlydeathinpatientswithwildtypetransthyretincardiacamyloidosis