P1640Longitudinal patterns of NT-proBNP, troponin T and CRP in relation to the dynamics of echocardiographic parameters in heart failure patients
Authors: Klimczak-Tomaniak D , Van Den Berg V , Strachinaru M , Akkerhuis K M , Baart S , Caliskan K , Manintveld O C , Umans V , Geleijnse M L , Boersma H , Van Dalen B , Kardys I 
Published: October 2019

Abstract

Introduction
Linking temporal biomarker evolutions to changes within myocardial structure and function could provide additional insights into the mechanisms that underlie associations between blood biomarkers and clinical outcome, which have been reported in previous studies.

Purpose
We aimed to investigate whether serum biomarkers reflect the functional state of the heart in a longitudinal setting. We examined the relationship between serial simultaneous measurements of echocardiographic parameters and serum biomarkers C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin t (hs-TnT) in chronic heart failure (CHF) patients.

Materials and methods
In total, 117 CHF patients enrolled in a prospective observational study underwent serial measurement of hs-TnT, NT-proBNP and CRP, accompanied by echocardiographic evaluation at six-month intervals until the end of 30-month follow-up or until an adverse clinical event (HF hospitalization, left ventricular assist device implantation, cardiac transplantation, cardiac death) occurred. Linear mixed effects (LME) models were used for data-analysis.

Results
Mean age was 58±11 years, 80% were male, 76% in NYHA class I or II and all had reduced left ventricular ejection fraction (LVEF). Median follow-up was 2.2 years [IQR: 1.5–2.6]. We performed up to 6 follow-up evaluations with 55% of patients having at least 3 evaluations performed. A model containing all three biomarkers revealed a significant, independent association between NT-proBNP and all the echocardiographic parameters, including LVEF (Beta coefficient per doubling of NT-proBNP [95% CI]: −0.12 [−0.16; −0.07] log2 (%EF), p<0.0001); mitral E/e' (0.17 [0.09; 0.24] log2 (change in ratio), p<0.0001); mitral E/A (0.22 [0.13; 0.30] log2 (change in ratio), p<0.0001); TAPSE (−0.06 [−0.11; −0.02] log2(mm), p=0.008), tricuspid regurgitation gradient (0.13 [0.07; 0.20] log2(mmHg), p=0.0001) as well as left ventricular and left atrial dimensions (p<0.001). Hs-TnT and CRP showed significant associations with some echocardiographic parameters after adjustment for clinical covariates, but associations lost significance after correction for the other biomarkers.
Figure 1. Associations between repeatedly measured NT-proBNP and repeatedly measured echocardiographic parameters (Panel A). Temporal evolution of echocardiographic parameters (B) and biomarker levels (C).

Conclusion
Serum NT-proBNP independently reflects temporal changes in echocardiographic parameters of systolic and diastolic function, left ventricular filling pressure, estimated pulmonary pressure and chamber diameters. Our results support further studies on NT-proBNP as a surrogate marker for hemodynamic congestion and herewith support its potential value for therapy guidance.

Acknowledgement/Funding
The Bio-SHiFT study was supported by the Jaap Schouten Foundation (Rotterdam, the Netherlands) and the Noordwest Academie (Alkmaar, the Netherlands).