# Association of preoperative Circulating biomarkers with echocardiographic measures of right ventricular strain five years after tetralogy of fallot repair

## TL;DR

This study explores how preoperative blood markers relate to heart function in children five years after heart surgery for tetralogy of Fallot.

## Contribution

The study identifies preoperative circulating biomarkers associated with mid-term right ventricular strain after tetralogy of Fallot repair.

## Key findings

- Higher preoperative levels of MMP1, PICP, and PIIINP were associated with worse right ventricular longitudinal strain.
- Higher NT-proBNP levels were associated with better free-wall systolic strain-rate.
- RV strain parameters remained stable until year 2, then declined significantly by years 3 to 5.

## Abstract

We analyzed right ventricular (RV) function using echocardiography after tetralogy of Fallot (TOF) repair to investigate the association between preoperative circulating biomarkers and RV strain five years after repair. We hypothesized that biomarkers of myocardial fibrosis and stretch would be correlated with worse mid-term RV function measured by strain.

We included children repaired at our institution from 2016 to 2019. Biomarkers measured preoperatively included galectin-3, Procollagen-type-I carboxy-terminal-propeptide (PICP), Procollagen-type-III-amino-terminal-propeptide (PIIINP), matrix-metalloproteinase-1 (MMP1), matrix-metalloproteinase-9 (MMP9), soluble suppression of tumorigenicity-2 (sST2), and N-terminal-pro-B-type-natriuretic-peptide (NT pro-BNP). Function was retrospectively assessed with RV longitudinal peak systolic strain (RVLS), free-wall peak systolic strain (FWS), peak systolic strain-rate (SR) and free-wall systolic strain-rate (FWSR) on available echocardiograms from one to five years after repair. Multivariable linear regression models with Generalized Estimating Equations tested whether preoperative biomarkers were associated with RV strain.

In total, 56 patients were followed with 198 reviewed echocardiograms, with a median of 4 echocardiograms per patient (range 1–5). Strain parameters remained stable until year 2 followed by a significant decrease in all parameters by year 3 through year 5. Higher preoperative levels of MMP1, PICP and PIIINP were associated with worse RVLS. Higher NT-proBNP was associated with better FWSR.

RV function is dynamic in the first 5 years after TOF repair but remains stable in the mid-term. Preoperative biomarkers of extracellular matrix turnover could help explain postoperative RV function in patients with TOF.

The online version contains supplementary material available at 10.1007/s10554-025-03533-4.