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
Year: 2025
Type: article
Abstract: 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.
Authors: Sophia Marie-Theres Dinges, Edzard Schwedhelm, Julia Schoenfeld, Andreas B Gevaert, Ephraim B Winzer, Bernhard Haller, Flavia Baldassarri, Axel Pressler, André Duvinage, Rainer Böger, Axel Linke, Volker Adams, Burkert Pieske, Frank Edelmann, Håvard Dalen, Torstein Hole, Alf Inge Larsen, Patrick Feiereisen, Trine Karlsen, Eva Prescott, Øyvind Ellingsen, Emeline M Van Craenenbroeck, Martin Halle, Stephan Mueller
Institutions: TUM Klinikum, German Centre for Cardiovascular Research, Technical University of Munich, University Medical Center Hamburg-Eppendorf, University of Antwerp, Antwerp University Hospital, Herzzentrum Dresden Universitätsklinik, Technische Universität Dresden, Universitätsmedizin Rostock, University of Rostock, Deutsches Herzzentrum der Charité, Norwegian University of Science and Technology, Levanger Hospital, St Olav's University Hospital, Helse Nord-Trøndelag HF, Ålesund Hospital, Stavanger University Hospital, University of Bergen, Centre Hospitalier de Luxembourg, Nord University, University of Copenhagen, Bispebjerg Hospital
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,792
Awards: G3127004584, G7218793668, G8412151466
OpenAlex ID: W4408420934