Abstract 3881: Determinants of Impaired Nitric Oxide Synthesis in Acute Decompensated Heart Failure
Background: Recent studies have identified strong clinical prognostic value of monitoring indices of dysregulated arginine metabolism. The hemodynamic determinants of dysregulated arginine metabolism in patients with progressive advanced decompensated heart failure are unclear.
Methods: We prospectively determined plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and the global arginine bioavailability ratio [GABR=Arginine/(Ornithine+Citrulline)] by tandem mass spectrometry in subjects with acute decompensated heart failure (“ADHF”, n=70) and with stable chronic systolic heart failure (“non-ADHF”, n=30).
Results: In our study cohort (mean age 55±13 years, 77% male, mean LVEF 29±9%), plasma ADMA (in median [interquartile range]) was significantly higher among ADHF (1.29 [1.04 –1.77] μM) vs non-ADHF (0.95 [0.84 –1.10] μM, p<0.0001), whereas GABR was significantly lower in ADHF subjects (0.92 [0.69 –1.23]) vs non-ADHF (1.03 [0.89 –1.37], p=0.029, Figure⇓). Among the hemodynamic variables in the ADHF group, mean pulmonary artery pressure (mPAP) was the strongest independent determinant of ADMA (odds ratio 8.5, 95%CI 2.64 –36.1, p<0.001), whereas central venous pressure provided the strongest determinant for GABR (odds ratio 1.98, 95%CI 1.13–3.78, p=0.02). Higher (mPAP>30 mmHg) was associated with higher ADMA levels (p=0.02) and lower GABR levels (p=0.03).
Conclusion: Dysregulated arginine metabolism was observed in decompensated heart failure, particularly in the setting of pulmonary hypertension and elevated intracardiac filling pressures.