Introduction: Symptomatic heart failure (HF) is associated with an elevation of biomarkers of venous congestion (proBNP and CD146), inflammation (endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα)), oxidative stress (isoprostane), endothelial activation (vascular cell adhesion molecule 1 (VCAM-1)). Of note, CD146 is the first biomarker reflecting systemic rather than central venous congestion in HF. The response of the above biomarkers to intensified diuretics in outpatients with acute decompensated HF (ADHF) has not been previously described.
Methods: We analyzed data from a randomized, double blind study enrolling 19 outpatients (age 62.68±12.40 yrs, 10 female) with symptoms of ADHF despite high dose loop diuretics. Patients were randomized to receive 7 days of either 100 or 25 mg of spironolactone daily and adjusted loop diuretic therapy (50% increase). Biomarkers were collected at day 1 and 7 and analyzed by ELISA or LC-MS.
Results: Intensified diuretics resulted in a significant reduction in weight (102±24 to 100±24 kg, p<0.0001), edema score (1.92±1.44 to 0.69±1.03, p=0.015), and JVP (16±2.9 to 12±2.5 cmH2O, p=0.002). Overall, VCAM-1, proBNP and CD146 tended to decline after decongestion (Figure). When stratified by median weight loss of 1.4kg, a significant decrease in isoprostane was observed (p=0.027). VCAM-1 and isoprostane tended to decline more in the high dose spironolactone group (p=NS). Of note, proBNP declined more (p<0.05) and CD146 tended to decline more (p=0.18) in patients who remain free from hospitalization at 90 days.
Conclusions: In outpatients with ADHF, serum biomarkers of congestion, oxidative stress and endothelial activation, but not inflammation, appear to decline in response to decongestion. Further studies are warranted to elucidate the prognostic significance with respect to clinical outcomes.