Effects of high-intensity interval training, moderate continuous training or usual care on ventilatory efficiency parameters in patients with heart failure with preserved ejection fraction

Abstract Background In patients with heart failure with preserved ejection fraction (HFpEF), ventilatory inefficiency is associated with worse prognosis, and may indicate co-existing pulmonary hypertension (PH) or a higher risk of developing PH. While different exercise training modes [e.g., moderate continuous training (MCT), high-intensity interval training (HIIT)] have been shown to improve peak oxygen uptake in HFpEF over 3-6 months, the effects on ventilatory efficiency are largely unknown. Purpose To investigate the effects of HIIT, MCT or usual care (UC) over 12 months on ventilatory efficiency in HFpEF. Methods In the OptimEx-Clin trial, 180 stable patients with HFpEF were randomly assigned to 12 months of HIIT (3×38 min/week with 4×4 min at 80-90% heart rate reserve [HRR]), MCT (5×40 min/week at 35-50% HRR) or UC (one-time advice on physical activity). Ventilatory efficiency parameters were assessed during symptom-limited cardiopulmonary exercise testing on a bicycle ergometer at baseline and follow-up. Ventilation to carbon dioxide production (V̇E/V̇CO2) slope and y-intercept were calculated between one minute of cycling and the second ventilatory threshold. The nadir of the ventilatory equivalent for CO2 (EqCO2) was defined as the lowest 60-second average during exercise. PetCO2 values were calculated as the lowest 60-second average at rest and the highest 60-second average during exercise. Statistical analyses were performed using dependent t-tests for within-group changes from baseline to 12 months, and analysis of variance and independent t-tests to compare the changes between groups. Analyses were done in R Statistical Software with α=0.05 and without adjusting for multiple testing. Results Among 180 randomized patients, 138 who had available CPET data both at baseline and 12-month follow-up (66% female; mean age, 70 years) were included in this secondary analysis. In the HIIT group, all investigated ventilatory efficiency parameters (V̇E/V̇CO2 slope, V̇E/V̇CO2 slope y-intercept, EqCO2 nadir, PetCO2 at rest and during exercise) significantly worsened from baseline to 12 months (P<0.05), while none were significantly altered following MCT or UC (Tab. 1). Group comparisons revealed significant differences between HIIT and MCT for change in V̇E/V̇CO2 slope [mean difference, +2.6 (95% CI, 0.8 to 4.5), global P=0.04)], V̇E/V̇CO2 slope y-intercept [-1.4 (95% CI, -2.5 to -0.3); global P=0.02)] and PetCO2 at rest [-2.0 mmHg (-3.5 to -0.5); global P=0.001)]. Moreover, change in PetCO2 at rest was also significantly different between HIIT and UC [-2.7 mmHg (-4.1 to -1.2)]. Conclusions In patients with HFpEF, ventilatory efficiency significantly worsened after 12 months of HIIT, which could be indicative of worsened heart failure prognosis and/or a shift towards PH – a frequent sequela of HFpEF.