Relationship between the expression levels of PITX2 and KCNQ1 in left atrial appendage tissue and the clinical characteristics in atrial fibrillation patients after modified mini-maze procedure_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIU Dingqian , GUO Changfa ,  WANG Chunsheng

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, P.R.China;

Corresponding author：

WANG Chunsheng, Email: wang.chunsheng@zs-hospital.sh.cn

Keywords：

Atrial fibrillation; mini-maze procedure; PITX2; KCNQ1

DOI：

10.7507/1007-4848.202011049

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To detect the expression of PITX2 and KCNQ1 in the left atrial appendage of patients with atrial fibrillation after modified mini-maze procedure, and to detect the clinical risk factors of different types of atrial fibrillation.Methods We collected left atrial appendage tissue of 59 atrial fibrillation patients who received modified mini-maze procedure and left atrial appendectomy from February 2017 to August 2018. The expression levels of PITX2 and KCNQ1 of left atrial appendage tissue were quantitatively analyzed by western blotting assay between paroxysmal attial fibrillation and persistent atrial fibrillation groups. The correlation between protein expression and prognosis after surgery was also analyzed based on clinical data.Results Binary-logistic regression analysis showed that KCNQ1 expression level was an independent risk factor for the progression from paroxysmal atrial fibrillation to persistent atrial fibrillation. Receiver operating characteristic (ROC) curve confirmed that KCNQ1 expression level (the ratio of KCNQ1 to actin in the analysis) was 0.60, which was the best cut-off point for the progression of paroxysmal atrial fibrillation to persistent atrial fibrillation.Conclusion High expression of KCNQ1 in left atrial appendage is a risk factor for progression from paroxysmal atrial fibrillation to persistent atrial fibrillation.

Citation： LIU Dingqian, GUO Changfa, WANG Chunsheng. Relationship between the expression levels of PITX2 and KCNQ1 in left atrial appendage tissue and the clinical characteristics in atrial fibrillation patients after modified mini-maze procedure. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(2): 158-163. doi: 10.7507/1007-4848.202011049 Copy

1.	Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
2.	Staerk L, Sherer JA, Ko D, et al. Atrial fibrillation: epidemiology, pathophysiology, and clinical outcomes. Circ Res, 2017, 120(9): 1501-1517.
3.	Robertson JO, Saint LL, Leidenfrost JE, et al. Illustrated techniques for performing the Cox-Maze Ⅳ procedure through a right mini-thoracotomy. Ann Cardiothorac Surg, 2014, 3(1): 105-116.
4.	Wolf RK, Burgess S. Minimally invasive surgery for atrial fibrillation-wolf mini maze procedure. Ann Cardiothorac Surg, 2014, 3(1): 122-123.
5.	Ismail I, Fleissner F, Cebotari S, et al. Left-sided mini-maze procedure via the left atrial appendage. Interact Cardiovasc Thorac Surg, 2014, 18(6): 847-849.
6.	Cox JL, Churyla A, Malaisrie SC, et al. When is a maze procedure a maze procedure? Can J Cardiol, 2018, 34(11): 1482-1491.
7.	Hayashi K, Tada H, Yamagishi M. The genetics of atrial fibrillation. Curr Opin Cardiol, 2017, 32(1): 10-16.
8.	Campbell HM, Wehrens XHT. Genetics of atrial fibrillation: an update. Curr Opin Cardiol, 2018, 33(3): 304-310.
9.	Roselli C, Chaffin MD, Weng LC, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet, 2018, 50(9): 1225-1233.
10.	Rani U, Praveen Kumar KS, Munisamaiah M, et al. Atrial fibrillation associated genetic variation near PITX2 gene increases the risk of preeclampsia. Pregnancy Hypertens, 2018, 13: 214-217.
11.	Gutierrez A, Chung MK. Genomics of atrial fibrillation. Curr Cardiol Rep, 2016, 18(6): 55.
12.	Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science, 2003, 299(5604): 251-254.
13.	Ma KJ, Li N, Teng SY, et al. Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism. Chin Med J (Engl), 2007, 120(2): 150-154.
14.	Li N, Dobrev D, Wehrens XH. PITX2: a master regulator of cardiac channelopathy in atrial fibrillation? Cardiovasc Res, 2016, 109(3): 345-347.
15.	Wijesurendra RS, Casadei B. Mechanisms of atrial fibrillation. Heart, 2019, 105(24): 1860-1867.
16.	Peng G, Barro-Soria R, Sampson KJ, et al. Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations. Sci Rep, 2017, 7: 45911.
17.	Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet, 2018, 50(9): 1234-1239.
18.	Campbell CM, Campbell JD, Thompson CH, et al. Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Circ Arrhythm Electrophysiol, 2013, 6(5): 960-966.
19.	Lee HC, Chiu CC, Chen CC, et al. Modulation of potassium channel KCNQ1 transcript in right atrial appendage of patients with postoperative atrial fibrillation. Int J Cardiol, 2016, 222: 696-698.
20.	Syeda F, Kirchhof P, Fabritz L. PITX2-dependent gene regulation in atrial fibrillation and rhythm control. J Physiol, 2017, 595(12): 4019-4026.
21.	Nadadur RD, Broman MT, Boukens B, et al. Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci Transl Med, 2016, 8(354): 354ra115.

1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
2. Staerk L, Sherer JA, Ko D, et al. Atrial fibrillation: epidemiology, pathophysiology, and clinical outcomes. Circ Res, 2017, 120(9): 1501-1517.
3. Robertson JO, Saint LL, Leidenfrost JE, et al. Illustrated techniques for performing the Cox-Maze Ⅳ procedure through a right mini-thoracotomy. Ann Cardiothorac Surg, 2014, 3(1): 105-116.
4. Wolf RK, Burgess S. Minimally invasive surgery for atrial fibrillation-wolf mini maze procedure. Ann Cardiothorac Surg, 2014, 3(1): 122-123.
5. Ismail I, Fleissner F, Cebotari S, et al. Left-sided mini-maze procedure via the left atrial appendage. Interact Cardiovasc Thorac Surg, 2014, 18(6): 847-849.
6. Cox JL, Churyla A, Malaisrie SC, et al. When is a maze procedure a maze procedure? Can J Cardiol, 2018, 34(11): 1482-1491.
7. Hayashi K, Tada H, Yamagishi M. The genetics of atrial fibrillation. Curr Opin Cardiol, 2017, 32(1): 10-16.
8. Campbell HM, Wehrens XHT. Genetics of atrial fibrillation: an update. Curr Opin Cardiol, 2018, 33(3): 304-310.
9. Roselli C, Chaffin MD, Weng LC, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet, 2018, 50(9): 1225-1233.
10. Rani U, Praveen Kumar KS, Munisamaiah M, et al. Atrial fibrillation associated genetic variation near PITX2 gene increases the risk of preeclampsia. Pregnancy Hypertens, 2018, 13: 214-217.
11. Gutierrez A, Chung MK. Genomics of atrial fibrillation. Curr Cardiol Rep, 2016, 18(6): 55.
12. Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science, 2003, 299(5604): 251-254.
13. Ma KJ, Li N, Teng SY, et al. Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism. Chin Med J (Engl), 2007, 120(2): 150-154.
14. Li N, Dobrev D, Wehrens XH. PITX2: a master regulator of cardiac channelopathy in atrial fibrillation? Cardiovasc Res, 2016, 109(3): 345-347.
15. Wijesurendra RS, Casadei B. Mechanisms of atrial fibrillation. Heart, 2019, 105(24): 1860-1867.
16. Peng G, Barro-Soria R, Sampson KJ, et al. Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations. Sci Rep, 2017, 7: 45911.
17. Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet, 2018, 50(9): 1234-1239.
18. Campbell CM, Campbell JD, Thompson CH, et al. Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Circ Arrhythm Electrophysiol, 2013, 6(5): 960-966.
19. Lee HC, Chiu CC, Chen CC, et al. Modulation of potassium channel KCNQ1 transcript in right atrial appendage of patients with postoperative atrial fibrillation. Int J Cardiol, 2016, 222: 696-698.
20. Syeda F, Kirchhof P, Fabritz L. PITX2-dependent gene regulation in atrial fibrillation and rhythm control. J Physiol, 2017, 595(12): 4019-4026.
21. Nadadur RD, Broman MT, Boukens B, et al. Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci Transl Med, 2016, 8(354): 354ra115.

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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Relationship between the expression levels of PITX2 and KCNQ1 in left atrial appendage tissue and the clinical characteristics in atrial fibrillation patients after modified mini-maze procedure

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