Increased exhaled nitric oxide levels after exercise in patients with chronic systolic heart failure with pulmonary venous hypertension

Background: Fractional exhaled nitric oxide (eNO) is recognized as a marker of pulmonary endothelial function. Oxidative stress is associated with systemic endothelial nitric oxide production, but its correlation with eNO in heart failure (HF) patients has not been described. Previous studies have reported increased eNO levels after exercise in symptomatic HF patients but decreased levels with pulmonary arterial hypertension. Our objective was to prospectively examine the potential myocardial and functional determinants of exercise-induced rise of eNO in HF. Methods and Results: Thirty-four consecutive ambulatory patients with chronic systolic HF (left ventricular ejection fraction [LVEF] ≤45%) underwent symptom-limited cardiopulmonary stress testing and echocardiography. eNO was determined immediately after exercise. Systemic endothelial dysfunction was assessed by asymmetric dimethylarginine (ADMA) and the L-arginine/ADMA ratio. In our study cohort (mean age 53 ± 13 years, 76% male, median LVEF 31%, interquartile range [IQR] 25%-40%), the mean eNO was 23 ± 9 ppb. eNO levels were higher in patients with diastolic dysfunction stages 2 or 3 than stage 1 or normal diastology (26.1 ± 9 vs 19.5 ± 7 ppb; P =.013). eNO had a positive correlation with estimated systolic pulmonary artery pressure (r = 0.57; P =.0009) and indexed left atrium volume (r = 0.43; P =.014), but it did not correlate with cardiopulmonary exercise test parameters, ADMA, or symptom score. Conclusions: In contrast to earlier reports, the increase in postexercise eNO observed in stable chronic systolic HF patients may be attributed to the presence of underlying pulmonary venous hypertension probably secondary to advanced diastolic dysfunction.