GDF15 IS LINKED TO CONGESTION-RELATED ANOREXIA AND WEIGHT LOSS IN ADVANCED HEART FAILURE

Background: Growth differentiation factor (GDF15) is a pleiotropic cytokine involved in cellular stress response. GDF15 in increased in plasma in chronic diseases including heart failure (HF) and it has a direct, appetite-suppressing effects in the brain. In experimental animals, reduction of GDF15 by an antibody prevents anorexia/weight loss in cancer or organ failure. Links of GDF15 levels to human cardiac cachexia are incompletely understood.

Methods: We examined 344 advanced HF patients (age 58±10y, NYHA 2.8±0.6, LVEF 22±5%), who underwent exam, MLHFQ, DEXA (n=150) and skinfold thickness assessment. GDF15 was measured by the Quantikine Assay (RD Systems). Patients were monitored for outcomes (death/urgent Tx/LVAD implantation, median fu: 39 months, IQR 13; 98).

Results: Mean GDF15 was 1835±1239 mg/l. Increased GDF15 was associated with poor event-free survival, particularly in the highest tercile (T3, >1916 mg/L). Among terciles, there was no difference in BMI. With growing GDF15 terciles, HF patients had markedly increased anorexia (MLHFQ question 11), larger BW loss in past 6mo and more of cardiac cachexia (BW loss> 5% in past 6mo: in 17, 39, 49%, <0.0001). Body composition indicated larger fat than fat-free mass loss. With higher GDF15, patients had increased BNP, FFA, beta-OH-butyrate, and glucagon, and lower albumin, cholesterol and insulin/glucagon ratio, consistent with a catabolic state. GDF15 terciles did not differ by LVEF%, but strongly differed in right ventricular (RV) dysfunction grade, right atrial (RA)/PAPW ratio and congestion score, indicating association of GDF15 with RV failure. 

Conclusions: Data support role of GDF15 as a putative target to prevent anorexia and weight loss in humans with HF. Increased GDF15 in HF is linked to right HF/congestion. Central GDF15 effects might explain congestion-related anorexia in HF.