Effects of exercise training on nitric oxide metabolites in heart failure with reduced or preserved ejection fraction: a secondary analysis of the SMARTEX-HF and OptimEx-Clin trials

Category	Detail
Condition	Heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF)
Key Mechanisms	Nitric oxide (NO) pathway regulation via metabolites L-arginine, homoarginine, ADMA, and SDMA affecting endothelial function
Target Population	Patients with HFrEF and HFpEF undergoing exercise training
Care Setting	Supervised exercise training programs in clinical trial settings

Baseline NO metabolite profiles differ between HFrEF and HFpEF, with higher homoarginine and ADMA in HFrEF.
NO metabolites correlate with heart failure severity markers (VO2peak, NT-proBNP) but not with endothelial function measures (FMD, reactive hyperaemia index).
Neither high-intensity interval training (HIIT) nor moderate continuous training (MCT) significantly altered NO metabolite plasma concentrations at 3 or 12 months.

Assess NO metabolite plasma concentrations (L-arginine, homoarginine, ADMA, SDMA) to understand endothelial dysfunction in HF.
Use VO2peak and NT-proBNP as markers of HF severity linked to NO metabolite profiles.

Implement supervised exercise training (HIIT or MCT) to improve exercise capacity in HF patients, recognizing no significant impact on NO metabolites.
Consider exercise training benefits independent of changes in NO metabolite levels.

Monitor exercise capacity (VO2peak) and NT-proBNP levels to evaluate HF severity and response to therapy.
Endothelial function measures (FMD, reactive hyperaemia index) may not reflect changes in NO metabolites.

No significant risks identified related to exercise training modes (HIIT or MCT) on NO metabolite levels in HF patients.

Patients with heart failure with reduced or preserved ejection fraction enrolled in supervised exercise programs

Exercise training (HIIT or MCT) does not significantly modify systemic NO metabolite concentrations despite improving clinical parameters.

Use exercise training to improve functional capacity in HF patients regardless of NO metabolite changes.
Recognize that NO metabolite profiles correlate with HF severity but are not modified by exercise training.
Evaluate endothelial dysfunction comprehensively, as NO metabolites and clinical endothelial function measures may not align.

Clinical Scorecard: Impact of Exercise Training on Nitric Oxide Metabolites in Heart Failure with Reduced and Preserved Ejection Fraction: Insights from the SMARTEX-HF and OptimEx-Clin Trials