Investigation of the prognostic value of GDF-3 ands Sortilin-1 in heart failure patients in relation to echocardiographic parameters, hospitalization, morbidity, and mortality

Heart failure is a clinical syndrome characterized by typical symptoms (such as dyspnea, reduced exercise tolerance, and fatigue) and signs (including pulmonary rales on auscultation, elevated jugular venous pressure, and peripheral edema) resulting from structural and/or functional abnormalities of the heart. The global prevalence of heart failure continues to rise, affecting approximately 1–3% of the adult population. This trend is driven by aging populations in developing countries, increasing rates of obesity, diabetes, and hypertension, and improved survival post-myocardial infarction. Patients diagnosed with heart failure with preserved ejection fraction (HFpEF) are typically over 65 years old, female, and have comorbidities such as diabetes, hypertension, atrial fibrillation, and obesity. The presence of coronary artery disease varies, but is generally less prevalent compared to patients with heart failure with reduced ejection fraction (HFrEF). Cardiac fibrosis plays a central role in the etiology of all heart failure types and is particularly prominent in the pathophysiology of HFpEF. Growth/differentiation factor 3 (GDF-3) is usually expressed at low levels in the normal adult heart and functions as a cytokine secreted into the extracellular space. Sortilin-1 (SORT1) is a multifunctional receptor implicated in both lipid metabolism and vascular inflammation, and is recognized for its role in the pathogenesis of cardiovascular diseases. In our study, we investigated the predictive value of these biomarkers (GDF-3 and Sortilin-1), which are associated with cardiac fibrosis and inflammation, for hospitalization and mortality in HFpEF patients. MATERİALS AND METHODS This study included 104 patients aged over 18, diagnosed with HFpEF (left ventricular ejection fraction ≥41%), who were admitted to Selçuk University Faculty of Medicine, Department of Cardiology. Participants had no history of active hematologic or oncologic malignancies, and had not experienced myocardial infarction within the past month. A control group consisting of 94 individuals with similar demographic characteristics but no heart failure diagnosis was also included. HFpEF-related parameters were assessed using transthoracic echocardiography. RESULTS In the multivariate Cox regression analysis conducted to evaluate predictors of hospitalization in HFpEF patients, GDF-3 remained statistically significant (HR = 1.007; 95% CI: 1.004–1.010; p < 0.001). Subsequent ROC curve analysis revealed an area under the curve (AUC) value of 0.691 for GDF-3 (p = 0.001), indicating statistical significance. Sensitivity and specificity values were determined as 73.2% and 50%, respectively. CONCLUSİON While GDF-3 emerged as a prognostic biomarker in HFpEF patients, the predictive power of Sortilin-1 in this group was found to be limited. The correlation of GDF-3 with both clinical outcomes and myocardial functional parameters such as global longitudinal strain (GLS) supports its potential utility in heart failure management. Further clinical research is needed to confirm the hypothesis regarding the use of GDF-3 as an early biomarker of cardiovascular events. Key Words: HEFpEF, Diastolic functions, GDF-3, Sortilin-1, Fibrosis