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Asymmetric Dimethyl-l-Arginine is a Biomarker for Disease Stage and Follow-Up of Pulmonary Hypertension Associated with Congenital Heart Disease

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Abstract

This study investigated the clinical value of plasma asymmetrical dimethyl-l-arginine (ADMA) level in the diagnosis, staging, and treatment response in congenital heart disease (CHD) patients with pulmonary arterial hypertension (PAH). This was a single-center prospective observational study in 80 CHD patients. Plasma ADMA levels were measured by enzyme-linked immunosorbent assay. Plasma ADMA levels were significantly increased in CHD patients with PAH compared with CHD patients without PAH (P < 0.01) and healthy controls (P < 0.001). In CHD patients with severe PAH, plasma ADMA levels were significantly higher in patients with Eisenmenger’s syndrome (ES) than in patients exhibiting low pulmonary vascular resistance (P < 0.001). The plasma ADMA levels significantly correlated with pulmonary arterial pressure (P < 0.001) and pulmonary vascular resistance (P < 0.001) in patients with CHD. Severe PAH was identified by plasma ADMA with a cutoff value of 0.485 μmol/L (P < 0.001) with a specificity of 82.8 % and a sensitivity of 90 %. ES was identified by plasma ADMA with a cutoff value of 0.85 μmol/L (P < 0.05) with a specificity of 85.2 % and a sensitivity of 64.3 %. ADMA levels were significantly decreased after sildenafil therapy for 6 months compared with before therapy levels (0.91 ± 0.22 vs. 0.57 ± 0.30, P < 0.01). Our study suggests that plasma ADMA level may be used as a biomarker for identifying PAH in patients with CHD, assessing pulmonary vascular remodeling, and evaluating the treatment response of CHD patients with PAH to sildenafil.

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Acknowledgments

The authors would like to thank Drs. Jiang Li, Yi Tang, and Jiming Zhou for their assistances in the study.

Conflict of interest

All the authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Authors and Affiliations

  1. Department of Cardiology, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, People’s Republic of China

    Zhen-fei Fang, Yi-yuan Huang, Liang Tang, Xin-qun Hu, Xiang-qian Shen, Jian-jun Tang & Sheng-hua Zhou

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  1. Zhen-fei Fang
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  2. Yi-yuan Huang
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  3. Liang Tang
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  4. Xin-qun Hu
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  7. Sheng-hua Zhou
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Correspondence to Sheng-hua Zhou.

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Fang, Zf., Huang, Yy., Tang, L. et al. Asymmetric Dimethyl-l-Arginine is a Biomarker for Disease Stage and Follow-Up of Pulmonary Hypertension Associated with Congenital Heart Disease. Pediatr Cardiol 36, 1062–1069 (2015). https://doi.org/10.1007/s00246-015-1127-3

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