Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment.

Silvia Oghina,Marc-Antoine Delbarre,Amira Zaroui,Mounira Kharoubi,François Montestruc,Mélanie Bézard,Thibaud Damy,Damien Eyharts,Pascale Fanen,Soulef Guendouz,Arnault Galat,Constant Josse,Luc Hittinger,Nadir Mouri,Emmanuel Teiger

doi:10.3390/jcm10214868

Abstract

Background: We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy (ATTR-CA) before and after tafamidis treatment. Methods and Results: 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 [0.57; 0.98]; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. Conclusion: ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.

Highlights

Transthyretin amyloid cardiomyopathy (ATTR-CA) is a systemic life-threatening disease characterized by amyloid fibrils accumulating in the heart [1]
For patients with cTnT-HS levels >50 ng/L, the slope before initiating tafamidis was 0.0185 compared to 0.0015
Our results show that NT-proBNP and cTnT-HS levels increase in ATTR-CA natural history and that 50%

Summary

Introduction

Transthyretin amyloid cardiomyopathy (ATTR-CA) is a systemic life-threatening disease characterized by amyloid fibrils accumulating in the heart [1]. There are two types of ATTR-CA: one hereditary (ATTRv-CA) with mutated genotypes for the protein transthyretin (TTR), and another with wild-type genotypes (ATTRwt-CA) [1]. TTR, mainly produced in the liver, transports the retinol-binding proteinvitamin A complex and to a lesser extent thyroxine. When TTR tetramer dissociates and the monomers misfolds TTR aggregates resulting in amyloidogenesis. Mutation of TTR (in ATTRv-CA) or aging (in ATTRwt-CA) destabilizers the tetramers and accelerate their dissociation into monomers. The TTR amyloid fibrils formed by the misfolding deposit in several tissues and organs in the body

Methods

Results

Conclusion