Soluble Urokinase Plasminogen Activator Receptor Is Associated With Subclinical Myocardial Impairment by Speckle Tracking Echocardiography in Lung Cancer Patients.

Ahmad S Manshad,Jochen Reiser,Tochukwu M Okwuosa,Jeffrey A Borgia,Fatima A Ballout

doi:10.3389/fcvm.2021.659524

Abstract

BackgroundPlasma cardiac biomarkers have emerged as a cost-effective diagnostic tool aimed at early identification of cardiotoxicity. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow cell derived signaling molecule that is associated with cardiovascular disease outcomes.ObjectivesWe investigated associations between suPAR and global longitudinal strain (GLS) as a marker of early myocardial impairment in lung cancer patients.MethodsWe retrospectively analyzed 52 patients with stage IV non-small cell lung cancer with normal left ventricular ejection fraction (LVEF >55%) and without known heart disease or end-stage renal disease (ESRD). We studied associations between cardiac biomarkers and echocardiographic measures of systolic and diastolic function. GLS was analyzed using 2D speckle-tracking echocardiography via vendor-independent software (TomTec).ResultsMedian plasma suPAR was 7.0 ng/mL (interquartile range: 5.4–9.0). Mean LVEF was 61.9 ± 8.3% and mean GLS was-19.3 ± 2.1%. Inter-observer reproducibility was excellent for GLS as determined by Intraclass Correlation Coefficient analysis, ICC = 0.81 (0.68–0.89). After multivariate analysis, suPAR was the only biomarker associated with GLS (p = 0.009). suPAR was also associated with diastolic parameters E velocity (p = 0.018), A velocity (p = 0.017), and E/E' ratio (p = 0.033). Interestingly, suPAR was not associated with LVEF (p = 0.916). In addition, suPAR and GLS were found to be age-independent predictors of all-cause mortality, though only GLS remained significant after multivariate adjustment.ConclusionsIn this cohort of stage IV non-small cell lung cancer patients with normal LVEF and without known heart disease or ESRD, suPAR was associated with GLS and diastolic impairment. suPAR is a readily available inexpensive biomarker; further research is required to evaluate the possible role of suPAR in screening for subclinical LV dysfunction in the high-risk oncological population.

Highlights

Current standards for detecting cancer-therapy induced cardiotoxicity are based on assessment of cardiac function by left ventricular ejection fraction (LVEF) using either transthoracic echocardiography (TTE) or radionuclide multigated acquisition (MUGA) [1, 2]
Higher Soluble urokinase plasminogen activator receptor (suPAR) levels were associated with history of smoking, use of diuretics, higher serum creatinine and lower eGFR, C-reactive protein (CRP), TNF-α, sAXL, and Angiopoietin-2. suPAR levels were not found to be associated with cancer duration, poorly differentiated histology, history of surgical resection, performance status, or radiation therapy
Inter-observer reproducibility was excellent for global longitudinal strain (GLS), intraclass correlation coefficient (ICC) = 0.81 (0.68–0.89). suPAR levels were not associated with LVEF (p = 0.862) in unadjusted comparisons (Figure 3)

Summary

Introduction

Current standards for detecting cancer-therapy induced cardiotoxicity are based on assessment of cardiac function by left ventricular ejection fraction (LVEF) using either transthoracic echocardiography (TTE) or radionuclide multigated acquisition (MUGA) [1, 2]. The assessment of LVEF lacks the sensitivity needed for detecting early subclinical changes. Newer echocardiographic modalities such as speckle tracking echocardiography (STE) enable earlier diagnosis of subclinical cardiac impairment not detected by conventional echocardiography [3]. Biomarkers have emerged as a new cost-effective diagnostic tool aimed at early identification of patients more prone to developing cardiotoxicity [6]. Soluble urokinase plasminogen activator receptor (suPAR) is gaining increasing attention because it is a circulating signaling molecule from the Ly6/neurotoxin family that is strongly predictive of incident and progressive chronic kidney disease and cancer cell progression [7,8,9,10]. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow cell derived signaling molecule that is associated with cardiovascular disease outcomes

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