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

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.

Automated summary

In lung cancer patients, plasma suPAR levels are associated with myocardial impairment and diastolic dysfunction, but not with left ventricular ejection fraction. Both suPAR and global longitudinal strain can predict all-cause mortality, but only global longitudinal strain remains significant after multivariate adjustment.