BACKGROUND: Heart failure (HF) is a chronic condition in which the heart does not pump enough blood to meet the bodys demands. Diffusing capacity of the lung for nitric oxide (DLNO) and carbon monoxide (DLCO) may be used to classify patients with HF, as DLNO and DLCO are lung function measurements that reflect pulmonary gas exchange. Our objectives were to determine 1) if DLNO added to DLCO testing predicts HF better than DLCO alone and 2) whether the binary classification of HF is better when DLNO z-scores are combined with DLCO z-scores than using DLCO z-scores alone. METHODS: This was a retrospective secondary data analysis in 140 New York Heart Association Class II HF patients (ejection fraction <40%) and 50 patients without HF. z-scores for DLNO, DLCO and DLNO+DLCO were created from reference equations from three articles. The model with the lowest Bayesian Information Criterion was the best predictive model. Binary HF classification was evaluated with the Matthews Correlation Coefficient (MCC). RESULTS: The top two of 12 models were combined z-score models. The highest MCC (0.51) was from combined z-score models. At most, only 32% of the variance in the odds of having HF was explained by combined z-scores. CONCLUSIONS: Combined z-scores explained 32% of the variation in the likelihood of an individual having HF, which was higher than models using DLNO or DLCO z-scores alone. Combined z-score models had a moderate ability to classify patients with HF. We recommend using the NO-CO double diffusion technique to assess gas exchange impairment in those suspected of HF.