Effect of Endothelin Receptor Antagonists on Recent Outcomes of Patients Undergoing Fontan Surgery: A Prospective Study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SHANGXiao-ke ¹ , ZHONGLiang ² , DINGShan-shan ³ ,  ZHANGGang-cheng ¹ , LURong ¹

1. Department of Cardiac Surgery, Wuhan Asia Heart Hospital Congenital Heart Center, Wuhan 430022, P. R. China;
2. National Heart Centre Singapore National Heart Research Institute of Singapore Duke-NUS Graduate Medical School, 169609 Singapore;
3. Cancer Center, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, P. R. China;

Corresponding author：

ZHANGGang-cheng, Email: Zhanggangchen@medmail.com.cn

Keywords：

Endothelin receptor antagonist; Fontan surgery; Total pulmonary resistance; Bosentan

DOI：

10.7507/1007-4848.20150059

Video：

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Objective To study the effect of endothelin receptor antagonist on recent outcome of patients undergoing Fontan surgery. Methods Thirty nine patients who received Fontan procedure from January 2009 to December 2010 in Wuhan Asia Heart Hospital were recruited in the study. There were 25 males and 14 females with mean age of 8.02±4.98 years (ranged from 2.5 to 18.0 years). According to the admission number, the patients were randomly divided into an endothelin receptor antagonists group (bosentan group, n=16) and a control group (n=23). The bosentan group received bosentan treatment by gastric fill or oral according to the recommended dose in three days after surgery for over 7 days. The control group did not receive any pulmonary hypertension targeted therapy. On the 10th day after surgery, indexes including mortality etc in the two groups were compared. Results No death occurred in the bosentan group. One patient died on the 5th day after operation in the control group. There was no significant difference in the postoperative mortality. The patients in the bosentan group got significantly better results than the control group in cardiac function, incidence of pleural effusion, vasoactive drugs score, and serum B-type natriuretic peptide, albumin, alanine aminotransferase on the 10th day (P < 0.05); while the 6-minute walk distance, transcutaneous oxygen saturation, white blood cell count, C-reactive protein, cardiac troponin I, and creatinine of the two groups showed no statistical difference (P > 0.05). Conclusion Endothelin receptor antagonists can improve the short-term outcome of patients after Fontan surgery.

Citation： SHANGXiao-ke, ZHONGLiang, DINGShan-shan, ZHANGGang-cheng, LURong. Effect of Endothelin Receptor Antagonists on Recent Outcomes of Patients Undergoing Fontan Surgery: A Prospective Study. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(3): 206-210. doi: 10.7507/1007-4848.20150059 Copy

1.	Ovaert C, Thijs D, Dewolf D.The effect of bosentan in patients with a failing Fontan circulation.Cardiol Young, 2009, 19(4):331-339.
2.	Schuuring MJ, Vis JC, Bouma BJ, et al.Rationale and design of a trial on the role of bosentan in Fontan patients:improvement of exercise capacity? Contemp Clin Trials, 2011, 32(4):586-591.
3.	汪曾炜, 刘维永, 张宝仁, 主编.人民军事医学出版社.心脏外科学, 2003.1149-1185.
4.	丁文祥, 苏肇伉, 史珍英, 主编.上海世界图书出版公司.小儿心脏外科重症监护手册, 2009.307-323.
5.	Tomita H, Yamada O, Ohuchi H, et al.Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.Cardiol Young, 2001, 11(1):62-66.
6.	邹明晖, 崔虎军, 马力, 等.改良Fontan手术治疗复杂先天性心脏病.中国胸心血管外科临床杂志, 2015, 22(1):39-43.
7.	孙国成, 郑奇军, 易定华, 等.应用系列改良Fontan手术治疗复杂先天性心脏病.中国胸心血管外科临床杂志, 2008, 15(6):406-410.
8.	周智恩, 孙小圣, 严善秀, 等.一氧化氮对Fontan类手术后肺血管阻力增高患者的治疗.中国胸心血管外科临床杂志, 2011, 18(2):156-156.
9.	Gewillig M.The Fontan circulation.Heart, 2005, 91(6):839-846.
10.	柳梅, 刘丽, 周红梅, 等.肝素治疗Fontan术后蛋白丢失性肠病一例.中华儿科杂志, 2009, 47(1):76-77.
11.	Mertens L, Hagler DJ, Sanuer U, et al.Protein-losing enteropathy after the Fontan operation:an international multicenter study.PLE study group.J Thorac Cardiovasc Surg, 1988, 115(5):1063-1073.
12.	郑景浩, 徐志伟, 刘锦纷, 等.改良侧通道Fontan手术在小儿复杂先天性心脏病中的应用.中国胸心血管外科临床杂志, 2009, 16(6):435-439.
13.	Ishida H, Kogaki S, Ichimori H, et al.Overexpression of endo thelin-1 and endothelin receptors in the pulmonary arteries of failed Fontan patients.Int J Cardiol, 2012, 159(1):34-39.
14.	Hebert A, Jensen AS, Idorn L, et al.The effect of bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study.BMC Cardiovasc Disord, 2013.doi:10.1186/1471-2261-13-36.
15.	Jasmin JF, Lucas M, Cernacek P, et al.Effectiveness of a nonselec tive ET (A/B) and a selective ET (A) antagonist in rats with monocro taline-induced pulmonary hypertension.Circulation, 2001, 103(2):314-318.
16.	Benza RL, Rayburn BK, Tallaj JA, et al.Efficacy of bosentan in a small cohort of adult patients with pulmonary arterial hypertension related to congenital heart disease.Chest, 2006, 129(4):1009-1015.
17.	Berger RM, Beghetti M, Galiè N, et al.Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome:a subgroup analysis.Int J Cardiol, 2010, 144(3):373-378.
18.	Bowater SE, Weaver RA, Thorne SA, et al.The safety and effects of bosentan in patients with a Fontan circulation.Congenit Heart Dis, 2012, 7(3):243-249.
19.	Hebert A, Jensen AS, Idorn L, et al.The effect of Bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study.BMC Cardiovasc Disord, 2013, 13(36):2-7.
20.	Cowie MR, Mendez GF.BNP and congestive heart failure.Prog Cardiovasc Dis, 2002, 44(4):293-321.
21.	Murphy JG, Gersh BJ, Mair DD, et al.Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot.N Engl J Med, 1993, 329(9):593-599.
22.	Maisel AS, Krishnaswamy P, Nowak RM, et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.N Engl J Med, 2002, 347(3):161-167.
23.	McCullough PA, Omland T, Maisel AS.B-type natriuretic peptides:A diagnostic breakthrough for clinicians.Rev Cardiovasc Med, 2003, 4(2):72-80.
24.	Law YM, Keller BB, Feingold BM, et al.Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease.Am J Cardiol, 2005, 95(4):474-478.
25.	Maisel AS.The diagnosis of acute congestive heart failure:role of BNP measurements.Heart Fail Rev, 2003, 8(4):327-334.

1. Ovaert C, Thijs D, Dewolf D.The effect of bosentan in patients with a failing Fontan circulation.Cardiol Young, 2009, 19(4):331-339.
2. Schuuring MJ, Vis JC, Bouma BJ, et al.Rationale and design of a trial on the role of bosentan in Fontan patients:improvement of exercise capacity? Contemp Clin Trials, 2011, 32(4):586-591.
3. 汪曾炜, 刘维永, 张宝仁, 主编.人民军事医学出版社.心脏外科学, 2003.1149-1185.
4. 丁文祥, 苏肇伉, 史珍英, 主编.上海世界图书出版公司.小儿心脏外科重症监护手册, 2009.307-323.
5. Tomita H, Yamada O, Ohuchi H, et al.Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations.Cardiol Young, 2001, 11(1):62-66.
6. 邹明晖, 崔虎军, 马力, 等.改良Fontan手术治疗复杂先天性心脏病.中国胸心血管外科临床杂志, 2015, 22(1):39-43.
7. 孙国成, 郑奇军, 易定华, 等.应用系列改良Fontan手术治疗复杂先天性心脏病.中国胸心血管外科临床杂志, 2008, 15(6):406-410.
8. 周智恩, 孙小圣, 严善秀, 等.一氧化氮对Fontan类手术后肺血管阻力增高患者的治疗.中国胸心血管外科临床杂志, 2011, 18(2):156-156.
9. Gewillig M.The Fontan circulation.Heart, 2005, 91(6):839-846.
10. 柳梅, 刘丽, 周红梅, 等.肝素治疗Fontan术后蛋白丢失性肠病一例.中华儿科杂志, 2009, 47(1):76-77.
11. Mertens L, Hagler DJ, Sanuer U, et al.Protein-losing enteropathy after the Fontan operation:an international multicenter study.PLE study group.J Thorac Cardiovasc Surg, 1988, 115(5):1063-1073.
12. 郑景浩, 徐志伟, 刘锦纷, 等.改良侧通道Fontan手术在小儿复杂先天性心脏病中的应用.中国胸心血管外科临床杂志, 2009, 16(6):435-439.
13. Ishida H, Kogaki S, Ichimori H, et al.Overexpression of endo thelin-1 and endothelin receptors in the pulmonary arteries of failed Fontan patients.Int J Cardiol, 2012, 159(1):34-39.
14. Hebert A, Jensen AS, Idorn L, et al.The effect of bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study.BMC Cardiovasc Disord, 2013.doi:10.1186/1471-2261-13-36.
15. Jasmin JF, Lucas M, Cernacek P, et al.Effectiveness of a nonselec tive ET (A/B) and a selective ET (A) antagonist in rats with monocro taline-induced pulmonary hypertension.Circulation, 2001, 103(2):314-318.
16. Benza RL, Rayburn BK, Tallaj JA, et al.Efficacy of bosentan in a small cohort of adult patients with pulmonary arterial hypertension related to congenital heart disease.Chest, 2006, 129(4):1009-1015.
17. Berger RM, Beghetti M, Galiè N, et al.Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to Eisenmenger's syndrome:a subgroup analysis.Int J Cardiol, 2010, 144(3):373-378.
18. Bowater SE, Weaver RA, Thorne SA, et al.The safety and effects of bosentan in patients with a Fontan circulation.Congenit Heart Dis, 2012, 7(3):243-249.
19. Hebert A, Jensen AS, Idorn L, et al.The effect of Bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study.BMC Cardiovasc Disord, 2013, 13(36):2-7.
20. Cowie MR, Mendez GF.BNP and congestive heart failure.Prog Cardiovasc Dis, 2002, 44(4):293-321.
21. Murphy JG, Gersh BJ, Mair DD, et al.Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot.N Engl J Med, 1993, 329(9):593-599.
22. Maisel AS, Krishnaswamy P, Nowak RM, et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.N Engl J Med, 2002, 347(3):161-167.
23. McCullough PA, Omland T, Maisel AS.B-type natriuretic peptides:A diagnostic breakthrough for clinicians.Rev Cardiovasc Med, 2003, 4(2):72-80.
24. Law YM, Keller BB, Feingold BM, et al.Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease.Am J Cardiol, 2005, 95(4):474-478.
25. Maisel AS.The diagnosis of acute congestive heart failure:role of BNP measurements.Heart Fail Rev, 2003, 8(4):327-334.

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Effect of Endothelin Receptor Antagonists on Recent Outcomes of Patients Undergoing Fontan Surgery: A Prospective Study

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