Supplementary Material for: Associations of small-airway disease with exercise intolerance and long-term outcomes in patients with heart failure and reduced or preserved ejection fraction

Introduction: Small airway is reportedly more susceptible than central airways in heart failure (HF), which may cause poor outcomes. We investigated clinical significance of small-airway disease (SAD) on exercise intolerance and clinical events in patients with HF and reduced or preserved left ventricular ejection fraction (LVEF). Methods: We studied consecutive patients with HF admitted for medical treatment and measured maximum mid-expiratory flow (MMEF) on spirometry and six-min walking distance (6MWD) at hospital discharge. SAD and exercise intolerance were defined by MMEF relative to <60% of the predicted value and 6MWD <300 m, respectively. Endpoint was composite clinical events of all-cause death and/or HF readmission. Results: Among 1016 studied patients, 478 (47.0%) had SAD, the prevalence of which was higher in patients with LVEF ≥40% than LVEF <40%. SAD correlated to 6MWD <300 m (adjusted odds ratio: 4.23, 95% confidence interval [CI]: 2.49–7.19). This correlation was consistently observed in both LVEF <40% (aOR: 3.99, 95% CI: 1.59–9.98) and LVEF ≥40% (aOR: 4.50, 95% CI:2.22–9.13). SAD also showed significant associations with high incidences of clinical events in all patients (adjusted hazard ratio [aHR]: 1.35, 95% CI: 1.05–1.72) and in LVEF <40% (aHR: 1.76, 95% CI: 1.21–2.54), but not in LVEF ≥40% (aHR: 1.10, 95% CI: 0.78–1.53). Conclusion: The prevalence of SAD is high in patients with HF, which is associated with exercise intolerance regardless of LVEF. Additionally, SAD may have a predictive significance for clinical events in these patients, especially in LVEF <40%.