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Relationship between exercise intervention and NO pathway in patients with heart failure with preserved ejection fraction
Baldassarri F, Schwedhelm E, Atzler D, Boger RH, Cordts K, Haller B, Pressler A, Muller S, Suchy C, Wachter R, Dungen HD, Hasenfuss G, Pieske B, Halle M, Edelmann F, Duvinage A
Biomarkers 2018 Sep;23(6):540-550
clinical trial
5/10 [Eligibility criteria: No; Random allocation: Yes; Concealed allocation: No; Baseline comparability: Yes; Blind subjects: No; Blind therapists: No; Blind assessors: No; Adequate follow-up: Yes; Intention-to-treat analysis: No; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

OBJECTIVE: Elevated levels of arginine derivatives in the NO pathway, such as asymmetric dimethylarginine (ADMA), are related to disease severity and reduced exercise capacity in heart failure (HF). We investigated the influence of exercise intervention on these parameters and on L-arginine (L-Arg) and L-homoarginine (L-hArg) in HF with preserved ejection fraction (HFpEF) patients. MATERIAL AND METHODS: Sixty-two patients (65 +/- 6 years) were included in this analysis and randomized to supervised endurance/resistance training (ET) or to usual care (UC). EDTA-plasma was analysed for NO metabolites. RESULTS: There were baseline associations for adjusted values of maximum workload with ADMA (r = -0.322, p = 0.028) and L-Arg/ADMA ratio (r = 0.331, p = 0.015), and for the 6-min walk test (6MWT) with ADMA (r = -0.314, p = 0.024) and L-Arg/ADMA ratio (r = 0.346, p = 0.015). No significant differences between UC and ET changes of NO parameters were observed at 3-month follow-up. Higher L-hArg levels were associated with a greater improvement in peak oxygen uptake (peakVO2) at follow-up: 3.4 +/- 2.8 versus 1.1 +/- 2.9 mL/min/kg (p = 0.005). CONCLUSIONS: Exercise intervention did not influence NO parameters in HFpEF patients, but L-hArg was related to change in peakVO2.

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