Key result
High-intensity interval and moderate continuous training fail to alter nitric oxide metabolite levels versus control.
Why the study?
The effects of different exercise modes on nitric oxide metabolites in patients with heart failure are uncertain.
Does exercise training (HIIT or MCT) improve nitric oxide metabolite profiles in patients with HFrEF or HFpEF?
RCT (n=366)
Does exercise training (HIIT or MCT) improve nitric oxide metabolite profiles in patients with HFrEF or HFpEF?
Exercise training (HIIT or MCT) does not significantly alter nitric oxide metabolite profiles in patients with HFrEF or HFpEF over 12 months.
Does not support exercise to target nitric oxide in HF; leaves open other mechanisms or adjunctive interventions.
AIMS: Exercise has been shown to affect the nitric oxide (NO) pathway, which is involved in the pathophysiology of endothelial dysfunction in heart failure (HF) with reduced (HFrEF) and preserved ejection fraction (HFpEF). However, the effects of different exercise modes on NO metabolites in patients with HF are uncertain. METHODS AND RESULTS: Blood samples from two randomized controlled HF trials evaluating (i) high-intensity interval training (HIIT), (ii) moderate continuous training (MCT), or (iii) a control group (CG) in HFrEF (SMARTEX-HF) and HFpEF (OptimEx-Clin) were analysed for NO metabolites L-arginine, homoarginine (hArg), asymmetric and symmetric dimethylarginine (ADMA; SDMA). Metabolite plasma concentrations were compared between HFrEF and HFpEF at baseline and within each HF type after 3 months of supervised exercise training and a 12-month follow-up. Overall, 206 patients with HFrEF (61 ± 12 years, 18.9% females) and 160 with HFpEF (70 ± 8 years, 65.6% females) were investigated. Baseline hArg (1.74 ± 0.78 vs. 1.31 ± 0.69 µmol/L) and ADMA (0.68 ± 0.15 vs. 0.62 ± 0.09 µmol/L) were significantly higher in HFrEF (P < 0.001). NO metabolites showed several significant associations with markers of HF severity like exercise capacity (VO2peak) and NT-proBNP, but not with measures of endothelial function (reactive hyperaemia index, flow-mediated dilation). After 3 months of exercise and a 12-month follow-up, changes in metabolite plasma levels were not significantly different between study groups (HIIT, MCT, or CG) (pgroup×time > 0.05), neither in HFrEF nor HFpEF. CONCLUSION: Baseline NO metabolite profile was unfavourable in patients with HF and lower VO2peak or higher NT-proBNP. We did not find a significant influence of HIIT or MCT on NO metabolites at 3 and 12 months.
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Dinges et al. (2025) conducted an RCT in Heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) (n=366). High-intensity interval training (HIIT) or moderate continuous training (MCT) vs. Control group (CG) was evaluated on Changes in nitric oxide metabolite plasma levels (L-arginine, homoarginine, ADMA, SDMA) (p=>0.05). High-intensity interval training and moderate continuous training did not significantly change nitric oxide metabolite plasma levels at 3 and 12 months compared to control (P>0.05).
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