Int J Med Sci 2020; 17(9):1147-1155. doi:10.7150/ijms.45795

Research Paper

N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial

Sintip Pattanakuhar1,2, Arintaya Phrommintikul1,3, Adisak Tantiworawit1,4, Somdet Srichairattanakool1,5, Siriporn C. Chattipakorn1,6, Nipon Chattipakorn1,6,7✉

1. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
2. Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
3. Division of Cardiology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
4. Division of Hematology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
5. Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
6. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
7. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

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Citation:
Pattanakuhar S, Phrommintikul A, Tantiworawit A, Srichairattanakool S, Chattipakorn SC, Chattipakorn N. N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial. Int J Med Sci 2020; 17(9):1147-1155. doi:10.7150/ijms.45795. Available from http://www.medsci.org/v17p1147.htm

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Abstract

Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.

Keywords: transfusion dependent thalassemia, N-acetylcysteine, heart rate variability, oxidative stress