Interleukin-1β levels predict long-term mortality and need for heart transplantation in ambulatory patients affected by idiopathic dilated cardiomyopathy.

Aneta Aleksova,Antonio Paolo Beltrami,Piergiuseppe Agostoni,Giulia Barbati,Piero Gentile,Elisabetta Salvioni,Pierluigi Lesizza,Miriam Isola,Cosimo Carriere,Tarcisio Not,Martina Perrieri-Montanino,Gianfranco Sinagra

doi:10.18632/oncotarget.15349

Abstract

AimsThe prognostic stratification of patients with Idiopathic Dilated Cardiomyopathy (iDCM) is a difficult task. Here, we assessed the additive value of the evaluation of biomarkers of inflammasome activation and systemic inflammation for the long-term risk stratification of iDCM patients.Methods and ResultsWe studied 156 ambulatory iDCM patients (mean age 58 years, 77% men, 79% in NYHA class 1-2, median Left Ventricular Ejection Fraction (LVEF) 35%, mean sodium 139 mEq/L, median BNP 189 pg/mL, median IL-1 beta (IL-1β) 1.08 pg/mL, median IL-6 1.7 pg/mL and median IL-10 2.7 pg/mL).During the follow-up period of 89.6 months, 35 patients (22%) died/underwent heart transplantation. Patients who died/underwent heart transplantation were more likely to be male, to be in NYHA class III, to have atrial fibrillation, to have lower LVEF and higher BNP levels. IL-1β, IL-6 and IL-10 levels did not differ significantly between the groups of patients with good or bad prognosis. IL-1β levels did not vary significantly among either the different NYHA classes or the quartiles of LVEF. In a multivariable model, however, IL-1β was a strong and independent predictor of all-cause mortality (HR 1.193, 95% CI 1.056 – 1.349, p=0.005 for log squared transformed values). Other factors associated with the outcome were: male gender, presence of atrial fibrillation and sodium concentration. The estimated time-dependent ROC curve of the multivariable model showed an AUC 0.74 (95% CI 0.65-0.86).ConclusionsSerum levels of IL-1β could be useful to predict the long-term outcome of patients with iDCM.

Highlights

Idiopathic Dilated Cardiomyopathy is the most frequent indication for cardiac transplantation [1]
IL-1β was a strong and independent predictor of all-cause mortality (HR 1.193, 95% Confidence Interval (CI) 1.056 – 1.349, p=0.005 for log squared transformed values)
The estimated time-dependent Receiver Operating Characteristics (ROC) curve of the multivariable model showed an Area Under Curve (AUC) 0.74

Summary

Introduction

Idiopathic Dilated Cardiomyopathy (iDCM) is the most frequent indication for cardiac transplantation [1]. Given the heterogeneity of the www.impactjournals.com/oncotarget pathogenic mechanisms that lead to cardiac remodeling and heart failure, emerging mechanisms responsible for disease progression may help to identify and validate helpful biomarkers to prognostically stratify patients. In this regard, the sterile inflammatory response that occurs as a result of the activation of the inflammasome is an emerging mechanism responsible for promoting cardiac remodeling and heart failure (reviewed in [3]). A recent small clinical study suggests that the evaluation of the activation status of the NLRP3 inflammasome may be employed to evaluate the shortterm outcome of patients affected by iDCM [4]

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Conclusion