Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response

A Sultan,J Wörmann,J -H V D Bruck,J Heijman,D Steven,M Mollenhauer,A Klinke,V Rudolph,S Baldus,T Ravekes,J Lüker,T Plenge

doi:10.1007/s00392-020-01690-1

Abstract

ObjectivesThis study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT.BackgroundCRT is a well-established treatment option in chronic heart failure (CHF) with 50–80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood.Methods Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up.Results Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml; p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml; p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman’s rho: − 0.453; p = 0.005) and physical capacity (Spearman’s rho: − 0.335; p = 0.042).ConclusionsResponse to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts.

Highlights

Chronic heart failure (CHF) is the major cause of mortality and morbidity in western society [1]
MPO levels correlate with a decrease in left ventricular ejection fraction (LVEF) and the severity of CHF [9]
As a main aspect in this study, we investigated a possible correlation between the courses of MPO levels and clinical response to cardiac resynchronization therapy (CRT) therapy

Summary

Introduction

Chronic heart failure (CHF) is the major cause of mortality and morbidity in western society [1]. Clinical Research in Cardiology response [5, 6] but so far are not established as tools to guide CRT implantation. Further trials aiming to establish NT-pro-BNP as a predictive marker produced significant results, but had poor sensitivity (62%) for CRT response; NT-pro-BNP could not be used as an effective preimplantation marker [8]. Released MPO leads to activation of macrophages and reactive oxygen species releasing PMN, perpetuating inflammatory processes, and left-ventricular remodeling [10]. MPO levels correlate with a decrease in left ventricular ejection fraction (LVEF) and the severity of CHF [9]. MPO is an independent predictor of 1-year mortality in patients with CHF and a risk factor for acute coronary syndrome (ACS) [11]. Improvement of physical capacity and LVEF remain the most valuable parameters for CRT response

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