The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?

BackgroundCardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT “response” and outcome. Our study investigated th...

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Main Authors: Matteo Beltrami, Alessandro Galluzzo, Riccardo Tappa Brocci, Alessandro Paoletti Perini, Paolo Pieragnoli, Manuel Garofalo, Geza Halasz, Massimo Milli, Maria Barilli, Alberto Palazzuoli
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1180960/full
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author Matteo Beltrami
Alessandro Galluzzo
Riccardo Tappa Brocci
Alessandro Paoletti Perini
Paolo Pieragnoli
Manuel Garofalo
Geza Halasz
Massimo Milli
Maria Barilli
Alberto Palazzuoli
author_facet Matteo Beltrami
Alessandro Galluzzo
Riccardo Tappa Brocci
Alessandro Paoletti Perini
Paolo Pieragnoli
Manuel Garofalo
Geza Halasz
Massimo Milli
Maria Barilli
Alberto Palazzuoli
author_sort Matteo Beltrami
collection DOAJ
description BackgroundCardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT “response” and outcome. Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.MethodsConsecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.ResultsAmong the 86 patients enrolled, 44% experienced the primary outcome. In this group, the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p < 0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p < 0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood. Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.ConclusionIn HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long-term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.
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spelling doaj.art-7080bcc3271645e98e8702d5ae089dd02023-06-12T04:22:21ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-06-011010.3389/fcvm.2023.11809601180960The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?Matteo Beltrami0Alessandro Galluzzo1Riccardo Tappa Brocci2Alessandro Paoletti Perini3Paolo Pieragnoli4Manuel Garofalo5Geza Halasz6Massimo Milli7Maria Barilli8Alberto Palazzuoli9Cardiology Unit, San Giovanni di Dio Hospital, Azienda USL Toscana Centro, Florence, ItalyCardiology Unit, Santa Croce Hospital, Moncalieri, ItalyDepartment of Clinical Trial, Le Scotte Hospital, University of Siena, Siena, ItalyDepartment of Internal Medicine, Cardiology and Electrophysiology Unit, Azienda USL Toscana Centro, Florence, ItalyArrhythmia and Electrophysiology Unit, Careggi University Hospital, Florence, ItalyDepartment of Clinical and Experimental Medicine, Careggi University Hospital, Florence, ItalyDepartment of Cardiosciences, Azienda Ospedaliera San Camillo-Forlanini, Rome, ItalyCardiology Unit, San Giovanni di Dio Hospital, Azienda USL Toscana Centro, Florence, ItalyDepartment of Medical Biotechnologies, Division of Cardiology, University of Siena, Le Scotte Hospital, Siena, ItalyCardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, Le Scotte Hospital, University of Siena, Siena, ItalyBackgroundCardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT “response” and outcome. Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.MethodsConsecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.ResultsAmong the 86 patients enrolled, 44% experienced the primary outcome. In this group, the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p < 0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p < 0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood. Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.ConclusionIn HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long-term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1180960/fullgalectin-3sST2eGFRbiomarkersheart failureoutcome
spellingShingle Matteo Beltrami
Alessandro Galluzzo
Riccardo Tappa Brocci
Alessandro Paoletti Perini
Paolo Pieragnoli
Manuel Garofalo
Geza Halasz
Massimo Milli
Maria Barilli
Alberto Palazzuoli
The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
Frontiers in Cardiovascular Medicine
galectin-3
sST2
eGFR
biomarkers
heart failure
outcome
title The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
title_full The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
title_fullStr The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
title_full_unstemmed The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
title_short The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
title_sort role of fibrosis inflammation and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy is response the right answer
topic galectin-3
sST2
eGFR
biomarkers
heart failure
outcome
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1180960/full
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