Plasma Growth Differentiation Factor-15 as a Prognostic Biomarker in Children with Congestive Heart Failure

Abstract

Aim and Objectives: This study aimed to evaluate the plasma levels of Growth Differentiation Factor-15 (GDF-15) in children with congestive heart failure, also to evaluate the diagnostic and prognostic value of this novel biomarker in pediatric congestive heart failure, by correlation of its levels with the clinical status and the echocardiographic data of these patients.
 Subjects and Methods: This study was conducted on Thirty (30) children with congestive heart failure (CHF), Patients were selected from those admitted to Pediatric Cardiology Unit, Pediatric Department, Tanta University Hospital, from (August 2018-April 2020), and thirty (30) healthy children, matched for age and sex, were enrolled as a control group. All children in this study were subjected to Plain X-ray chest and heart: Cardiothoracic ratio (CTR) was measured, and Echocardiographic assessment: Doppler and Two-dimensional, M-mode Echocardiographic evaluation of these parameters and Plasma level of Growth Differentiation Factor-15 (GDF-15) was measured. 
 Results: the results revealed that The best cutoff point of GDF-15 to differentiate between cases with CHF and control group was >446.5 ng/l with 93.33% sensitivity, 90% specificity, 90.3% PPV, 93.1% NPV and AUC was 0.992.
 There was significant decrease of EF% and FS% (systolic dysfunction of LV) in patients with CHF as compared to control group.
 There was statistically significant positive correlation between plasma level of GDF-15 and Ross clinical stage of CHF.
 There was statistically significant negative correlation between GDF-15 and EF%, FS % by echocardiography.
 Conclusion: Plasma levels of GDF-15 were elevated in children with CHF, and these levels were correlated to the Ross staging of CHF and echocardiographic assessment of LV function. Plasma levels of GDF-15 were elevated in patients with bad prognosis, denoting its prognostic value as a novel biomarker in pediatric CHF.

Exploring the Link Between the Serum/Blood Levels of Heavy Metals (Pb, As, Cd, and Cu) and 2 Novel Biomarkers of Cardiovascular Stress (Growth Differentiation Factor 15 and Soluble Suppression of Tumorigenicity 2) in Copper Smelter Workers

“…Consistent with results found in the prior literature, the cutoff points of GDF-15 and sST2 for predicting total cardiovascular events were approximately 2000 pg/mL and 30 ng/mL, respectively 38,92 . Although the only limitation of using both biomarkers is their lack of cardiovascular specificity, previous studies reported satisfying figures of their specificity and sensitivity in predicting cardiovascular events 38–40 …”

“…38,92 Although the only limitation of using both biomarkers is their lack of cardiovascular specificity, previous studies reported satisfying figures of their specificity and sensitivity in predicting cardiovascular events. [38][39][40] The study findings also drew attention to the impact of occupational exposure to toxic heavy metals on the cardiovascular system in a possible dose and time-dependent manner. Significant correlations between heavy metal concentrations, duration of employment, and levels of both studied biomarkers were found.…”

“…Recently, the predictive values of both novel biomarkers have been studied and evaluated frequently in heart failure in both adult and pediatric patients. The results revealed that the sensitivity of GDF-15 to differentiate between cases with congestive heart failure and control group was greater than 90% with greater than 80% specificity, and the AUC from the ROC curves had values greater than 0.9, whereas the sensitivity of sST2 was approximately 70% with specificity greater than 50% and an AUC of value greater than 0.7 38–40 …”

“…The results revealed that the sensitivity of GDF-15 to differentiate between cases with congestive heart failure and control group was greater than 90% with greater than 80% specificity, and the AUC from the ROC curves had values greater than 0.9, whereas the sensitivity of sST2 was approximately 70% with specificity greater than 50% and an AUC of value greater than 0.7. [38][39][40] Consequently, this study aimed to explore the association between the serum/blood levels of the heavy metals (Pb, As, Cd, and Cu) and the serum levels of both biomarkers (GDF-15 and sST2) in the workers of the studied smelter. The detected association might draw the attention to a potential risk to develop future cardiovascular stressful events among those studied Cu smelter workers because of their occupational exposure to Pb, As, Cd, and Cu.…”

Paediatric heart failure – understanding the pathophysiology and the current role of cardiac biomarkers in clinical practice

“…Elevated growth differentiation factor-15 levels can be used to accurately identify participants at highest risk of adverse cardiac events or death. 36,100,101 Growth differentiation factor-15 levels correlated positively with NT-proBNP levels, and one study highlighted that when used in combination with NT-proBNP and hsTnT it could be used to identify those participants at highest risk of adverse events compared to using NT-proBNP alone. 102 However, as only some of the studies directly compared diagnostic accuracy of NT-proBNP and growth differentiation factor-15 in paediatric heart failure, it would appear that NT-proBNP remains more sensitive and specific for those with heart failure and biventricular physiology.…”