LAUSR

Background Minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), as assessed by cardiopulmonary exercise testing (CPET), strongly predicts outcomes in heart failure (HF). High VE/VCO2 slope can indicate ventilatory inefficiency. A single VE/VCO2 slope threshold defining abnormal of ≥ 34 to 36 is used clinically across HF categories; however, this threshold has been validated largely in patients with reduced left ventricular ejection fraction (LVEF). Objectives To examine the associations between VE/VCO2 slope categories and a composite outcome of all-cause mortality and HF hospitalization across the spectrum of HF patients defined by LVEF. Methods Single-center retrospective cohort study of 1347 patients with heart failure (60.5% male, age 58.0±14.6 years, LVEF 42 ± 17%) clinically referred for CPET between 2010 and 2016. LVEF was obtained from echocardiogram (n=1309) or cardiac MRI (n=38). All-cause mortality was determined using Partners Research Patient Data Registry, which is linked to National Death Index. HF hospitalization data were adjudicated by review of electronic medical record. Patients with HF were categorized based on LVEF into heart failure with reduced (HFrEF, LVEF Results At two-year follow-up post CPET, there were 197 composite events (64 deaths and 133 HF hospitalizations). Across the entire cohort, increases in VC category were associated with increasing risk of two-year composite outcome in unadjusted and adjusted models. Compared to patients in VC-I, patients in VC-II were at increased risk of having two-year composite outcome in both HFrEF and HFpEF cohorts. Patients in VC III and IV had incremental increases in the likelihood of two-year composite outcome across all three HF cohorts (Table). Conclusions Higher VE/VCO2 slope categories are associated with increased risk of the two-year composite outcome of all-cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A VE/VCO2 slope between 29 and 36, often considered borderline in clinical practice, is associated with increased risk of this composite outcome in patients with HFrEF and HFpEF. Identifying a wider VE/VCO2 slope associated with increased risk in HF may have important implications on risk stratification clinically.