Analysis of risk factors and prediction model construction of arrhythmia after esophagectomy_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LI Juan , LIU Xiaolong , WU Xianning , MEI XinYu ,  YUAN Ligong

Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei, 230001, P. R. China;

Corresponding author：

YUAN Ligong, Email: yligong@ustc.edu.cn

Keywords：

Esophageal cancer; arrhythmia; risk prediction model; pneumonia

DOI：

10.7507/1007-4848.202504008

Video：

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Objective To analyze the risk factors affecting the occurrence of arrhythmia after esophageal cancer surgery, construct a risk prediction model, and explore its clinical value. Methods A retrospective analysis was conducted on the clinical data of patients who underwent radical esophagectomy for esophageal cancer in the Department of Thoracic Surgery at Anhui Provincial Hospital from 2020 to 2023. Univariate and multivariate analyses were used to screen potential factors influencing postoperative arrhythmia. A risk prediction model for postoperative arrhythmia was constructed, and a nomogram was drawn. The predictive performance of the model was then validated. Results A total of 601 esophageal cancer patients were randomly divided into a modeling group (421 patients) and a validation group (180 patients) at a 7 : 3 ratio. In the modeling group, patients were further categorized into an arrhythmia group (188 patients, 44.7%) and a non-arrhythmia group (233 patients, 55.3%) based on whether they developed postoperative arrhythmia. Among those with postoperative arrhythmia, 43 (10.2%) patients had atrial fibrillation (AF), 12 (2.9%) patients had atrial premature beats, 15 (3.6%) patients had sinus bradycardia, and 143 (34%) patients had sinus tachycardia. Some patients exhibited multiple arrhythmias, including 14 patients with AF combined with sinus tachycardia, 7 patients with AF combined with atrial premature beats, and 3 patients with AF combined with sinus bradycardia. Univariate analysis revealed that a history of hypertension, heart disease, pulmonary infection, acute respiratory distress syndrome, postoperative hypoxia, anastomotic leakage, and delirium were risk factors for postoperative arrhythmia in esophageal cancer patients (P<0.05). Multivariate logistic regression analysis showed that a history of heart disease, pulmonary infection, and postoperative hypoxia were independent risk factors for postoperative arrhythmia after esophageal cancer surgery (P<0.05). The area under the receiver operating characteristic curve (AUC) of the constructed risk prediction model for postoperative arrhythmia was 0.710 [95% CI (0.659, 0.760)], with a sensitivity of 0.617 and a specificity of 0.768. Conclusion A history of heart disease, pulmonary infection, and postoperative hypoxia are independent risk factors for postoperative arrhythmia after esophageal cancer surgery. The risk prediction model constructed in this study can effectively identify high-risk patients for postoperative arrhythmia, providing a basis for personalized interventions.

1.	Zheng RS, Chen R, Han BF, et al. Cancer incidence and mortality in China, 2022. Chin J Oncol, 2024, 46(3): 221-231.
2.	Yang H, Wang F, Hallemeier CL, et al. Oesophageal cancer. Lancet, 2024, 404(10466): 1991-2005.
3.	Low DE, Kuppusamy MK, Alderson D, et al. Benchmarking complications associated with esophagectomy. Ann Surg, 2019, 269(2): 291-298.
4.	周浩, 胡青. 189例老年食管癌根治手术后发生心律失常的危险因素探讨. 中国医师杂志, 2019, 21(12): 1857-1860.
5.	国家卫生健康委员会. 食管癌诊疗规范(2018年版). 中华消化病与影像杂志, 2019, 9(4): 158-192.
6.	Rühlmann F, Tichelbäcker T, Mackert AF, et al. Incidence, associated risk factors, and outcomes of postoperative arrhythmia after upper gastrointestinal surgery. JAMA Netw Open, 2022, 5(7): e2223225.
7.	Alturki A, Marafi M, Proietti R, et al. Major adverse cardiovascular events associated with postoperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol, 2020, 13(1): e007437.
8.	Ma JY, Wang Y, Zhao YF, et al. Atrial fibrillation after surgery for esophageal carcinoma: clinical and prognostic significance. World J Gastroenterol, 2006, 12(3): 449-452.
9.	Nagatsuka Y, Sugimura K, Miyata H, et al. Predictive value of preoperative echocardiographic assessment for postoperative atrial fibrillation after esophagectomy for esophageal cancer. Esophagus, 2021, 18(3): 496-503.
10.	Day RW, Jaroszewski D, Chang YH, et al. Incidence and impact of postoperative atrial fibrillation after minimally invasive esophagectomy. Dis Esophagus, 2016, 29(6): 583-588.
11.	Rao VP, Addae-Boateng E, Barua A, et al. Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy. Eur J Cardiothorac Surg, 2012, 42(3): 438-443.
12.	Takase B, Ikeda T, Shimizu W, et al. JCS/JHRS 2022 Guideline on diagnosis and risk assessment of arrhythmia. Circ J, 2024, 88(9): 1509-1595.
13.	Maesen B, Nijs J, Maessen J, et al. Post-operative atrial fibrillation: a maze of mechanisms. Europace, 2012, 14(2): 159-174.
14.	Stawicki SP, Prosciak MP, Gerlach AT, et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity. Gen Thorac Cardiovasc Surg, 2011, 59(6): 399-405.
15.	Wells CI, Robertson JP, Campbell S, et al. Impact of atrial fibrillation on long-term survival following oesophagectomy: a 21-year observational study. ANZ J Surg, 2018, 88(4): E268-E272.
16.	Hou JL, Gao K, Li M, et al. Increased N-terminal pro-brain natriuretic peptide level predicts atrial fibrillation after surgery for esophageal carcinoma. World J Gastroenterol, 2008, 14(16): 2582-2585.
17.	Tang J, Zhao JZ, Ren KM, et al. Risk factors of atrial fibrillation occurring after radical surgery of esophageal carcinoma. J Cardiothorac Surg, 2019, 14(1): 60.
18.	Bessissow A, Khan J, Devereaux PJ, et al. Postoperative atrial fibrillation in non-cardiac and cardiac surgery: an overview. J Thromb Haemost, 2015, 13 Suppl 1: S304-S312.
19.	Boshier PR, Marczin N, Hanna GB. Pathophysiology of acute lung injury following esophagectomy. Dis Esophagus, 2015, 28(8): 797-804.
20.	D'Journo XB, Michelet P, Avaro JP, et al. Respiratory complications after oesophagectomy for cancer. Rev Mal Respir, 2008, 25(6): 683-694.
21.	Grimminger PP, Goense L, Gockel I, et al. Diagnosis, assessment, and management of surgical complications following esophagectomy. Ann N Y Acad Sci, 2018, 1434(1): 254-273.
22.	Roberts JR. Postoperative respiratory failure. Thorac Surg Clin, 2006, 16(3): 235-241.
23.	Law S, Wong KH, Kwok KF, et al. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg, 2004, 240(5): 791-800.
24.	Ma LY, Liao ZF, Wang GJ. Risk factors for post-surgical pulmonary complications in patients after esophagectomy for cancer: a multivariate logistic analysis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2011, 23(10): 625-628.
25.	Avendano CE, Flume PA, Silvestri GA, et al. Pulmonary complications after esophagectomy. Ann Thorac Surg, 2002, 73(3): 922-926.
26.	van Dessel E, Moons J, Nafteux P, et al. Perioperative fluid management in esophagectomy for cancer and its relation to postoperative respiratory complications. Dis Esophagus, 2021, 34(7): doaa111.
27.	Heinzinger CM, Thompson NR, Milinovich A, et al. Sleep-disordered breathing, hypoxia, and pulmonary physiologic influences in atrial fibrillation. J Am Heart Assoc, 2023, 12(22): e031462.
28.	Saleeb-Mousa J, Nathanael D, Coney AM, et al. Mechanisms of atrial fibrillation in obstructive sleep apnoea. Cells, 2023, 12(12): 1661.
29.	Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: pathophysiological mechanisms and therapeutic implications. Int J Cardiol, 2017, 230: 293-300.
30.	Lee KY, Ho SW, Wang YH, et al. Risk of atrial fibrillation in patients with pneumonia. Heart Lung, 2022, 52: 110-116.
31.	Dukhinova M, Kokinos E, Kuchur P, et al. Macrophage-derived cytokines in pneumonia: linking cellular immunology and genetics. Cytokine Growth Factor Rev, 2021, 59: 46-61.
32.	Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet, 2022, 400(10358): 1145-1156.
33.	Lazzerini PE, Abbate A, Boutjdir M, et al. Fir(e)ing the rhythm: inflammatory cytokines and cardiac arrhythmias. JACC Basic Transl Sci, 2023, 8(6): 728-750.
34.	Seesing MFJ, Scheijmans JCG, Borggreve AS, et al. The predictive value of new-onset atrial fibrillation on postoperative morbidity after esophagectomy. Dis Esophagus, 2018, 31(11).
35.	Stawicki SPA, Prosciak MP, Gerlach AT, et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity. Gen Thorac Cardiovasc Surg, 2011, 59(6): 399-405.
36.	Murthy SC, Law S, Whooley BP, et al. Atrial fibrillation after esophagectomy is a marker for postoperative morbidity and mortality. J Thorac Cardiovasc Surg, 2003, 126(4): 1162-1167.
37.	Stippel DL, Taylan C, Schröder W, et al. Supraventricular tachyarrhythmia as early indicator of a complicated course after esophagectomy. Dis Esophagus, 2005, 18(4): 267-273.
38.	Walsh SR, Tang T, Wijewardena C, et al. Postoperative arrhythmias in general surgical patients. Ann R Coll Surg Engl, 2007, 89(2): 91-95.
39.	Cardinale D, Sandri MT, Colombo A, et al. Prevention of atrial fibrillation in high-risk patients undergoing lung cancer surgery: the PRESAGE trial. Ann Surg, 2016, 264(2): 244-251.
40.	Bayliff CD, Massel DR, Inculet RI, et al. Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. Ann Thorac Surg, 1999, 67(1): 182-186.
41.	Ojima T, Nakamori M, Nakamura M, et al. Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer. Br J Surg, 2017, 104(8): 1003-1009.
42.	Tisdale JE, Wroblewski HA, Wall DS, et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. J Thorac Cardiovasc Surg, 2010, 140(1): 45-51.
43.	Amar D, Zhang H, Chung MK, et al. Amiodarone with or without N-acetylcysteine for the prevention of atrial fibrillation after thoracic surgery: a double-blind, randomized trial. Anesthesiology, 2022, 136(6): 916-926.
44.	Tisdale JE, Jaynes HA, Watson MR, et al. Amiodarone for prevention of atrial fibrillation following esophagectomy. J Thorac Cardiovasc Surg, 2019, 158(1): 301-310. e1.
45.	Tisdale JE, Wroblewski HA, Kesler KA. Prophylaxis of atrial fibrillation after noncardiac thoracic surgery. Semin Thorac Cardiovasc Surg, 2010, 22(4): 310-320.

1. Zheng RS, Chen R, Han BF, et al. Cancer incidence and mortality in China, 2022. Chin J Oncol, 2024, 46(3): 221-231.
2. Yang H, Wang F, Hallemeier CL, et al. Oesophageal cancer. Lancet, 2024, 404(10466): 1991-2005.
3. Low DE, Kuppusamy MK, Alderson D, et al. Benchmarking complications associated with esophagectomy. Ann Surg, 2019, 269(2): 291-298.
4. 周浩, 胡青. 189例老年食管癌根治手术后发生心律失常的危险因素探讨. 中国医师杂志, 2019, 21(12): 1857-1860.
5. 国家卫生健康委员会. 食管癌诊疗规范(2018年版). 中华消化病与影像杂志, 2019, 9(4): 158-192.
6. Rühlmann F, Tichelbäcker T, Mackert AF, et al. Incidence, associated risk factors, and outcomes of postoperative arrhythmia after upper gastrointestinal surgery. JAMA Netw Open, 2022, 5(7): e2223225.
7. Alturki A, Marafi M, Proietti R, et al. Major adverse cardiovascular events associated with postoperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol, 2020, 13(1): e007437.
8. Ma JY, Wang Y, Zhao YF, et al. Atrial fibrillation after surgery for esophageal carcinoma: clinical and prognostic significance. World J Gastroenterol, 2006, 12(3): 449-452.
9. Nagatsuka Y, Sugimura K, Miyata H, et al. Predictive value of preoperative echocardiographic assessment for postoperative atrial fibrillation after esophagectomy for esophageal cancer. Esophagus, 2021, 18(3): 496-503.
10. Day RW, Jaroszewski D, Chang YH, et al. Incidence and impact of postoperative atrial fibrillation after minimally invasive esophagectomy. Dis Esophagus, 2016, 29(6): 583-588.
11. Rao VP, Addae-Boateng E, Barua A, et al. Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy. Eur J Cardiothorac Surg, 2012, 42(3): 438-443.
12. Takase B, Ikeda T, Shimizu W, et al. JCS/JHRS 2022 Guideline on diagnosis and risk assessment of arrhythmia. Circ J, 2024, 88(9): 1509-1595.
13. Maesen B, Nijs J, Maessen J, et al. Post-operative atrial fibrillation: a maze of mechanisms. Europace, 2012, 14(2): 159-174.
14. Stawicki SP, Prosciak MP, Gerlach AT, et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity. Gen Thorac Cardiovasc Surg, 2011, 59(6): 399-405.
15. Wells CI, Robertson JP, Campbell S, et al. Impact of atrial fibrillation on long-term survival following oesophagectomy: a 21-year observational study. ANZ J Surg, 2018, 88(4): E268-E272.
16. Hou JL, Gao K, Li M, et al. Increased N-terminal pro-brain natriuretic peptide level predicts atrial fibrillation after surgery for esophageal carcinoma. World J Gastroenterol, 2008, 14(16): 2582-2585.
17. Tang J, Zhao JZ, Ren KM, et al. Risk factors of atrial fibrillation occurring after radical surgery of esophageal carcinoma. J Cardiothorac Surg, 2019, 14(1): 60.
18. Bessissow A, Khan J, Devereaux PJ, et al. Postoperative atrial fibrillation in non-cardiac and cardiac surgery: an overview. J Thromb Haemost, 2015, 13 Suppl 1: S304-S312.
19. Boshier PR, Marczin N, Hanna GB. Pathophysiology of acute lung injury following esophagectomy. Dis Esophagus, 2015, 28(8): 797-804.
20. D'Journo XB, Michelet P, Avaro JP, et al. Respiratory complications after oesophagectomy for cancer. Rev Mal Respir, 2008, 25(6): 683-694.
21. Grimminger PP, Goense L, Gockel I, et al. Diagnosis, assessment, and management of surgical complications following esophagectomy. Ann N Y Acad Sci, 2018, 1434(1): 254-273.
22. Roberts JR. Postoperative respiratory failure. Thorac Surg Clin, 2006, 16(3): 235-241.
23. Law S, Wong KH, Kwok KF, et al. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg, 2004, 240(5): 791-800.
24. Ma LY, Liao ZF, Wang GJ. Risk factors for post-surgical pulmonary complications in patients after esophagectomy for cancer: a multivariate logistic analysis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2011, 23(10): 625-628.
25. Avendano CE, Flume PA, Silvestri GA, et al. Pulmonary complications after esophagectomy. Ann Thorac Surg, 2002, 73(3): 922-926.
26. van Dessel E, Moons J, Nafteux P, et al. Perioperative fluid management in esophagectomy for cancer and its relation to postoperative respiratory complications. Dis Esophagus, 2021, 34(7): doaa111.
27. Heinzinger CM, Thompson NR, Milinovich A, et al. Sleep-disordered breathing, hypoxia, and pulmonary physiologic influences in atrial fibrillation. J Am Heart Assoc, 2023, 12(22): e031462.
28. Saleeb-Mousa J, Nathanael D, Coney AM, et al. Mechanisms of atrial fibrillation in obstructive sleep apnoea. Cells, 2023, 12(12): 1661.
29. Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: pathophysiological mechanisms and therapeutic implications. Int J Cardiol, 2017, 230: 293-300.
30. Lee KY, Ho SW, Wang YH, et al. Risk of atrial fibrillation in patients with pneumonia. Heart Lung, 2022, 52: 110-116.
31. Dukhinova M, Kokinos E, Kuchur P, et al. Macrophage-derived cytokines in pneumonia: linking cellular immunology and genetics. Cytokine Growth Factor Rev, 2021, 59: 46-61.
32. Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet, 2022, 400(10358): 1145-1156.
33. Lazzerini PE, Abbate A, Boutjdir M, et al. Fir(e)ing the rhythm: inflammatory cytokines and cardiac arrhythmias. JACC Basic Transl Sci, 2023, 8(6): 728-750.
34. Seesing MFJ, Scheijmans JCG, Borggreve AS, et al. The predictive value of new-onset atrial fibrillation on postoperative morbidity after esophagectomy. Dis Esophagus, 2018, 31(11).
35. Stawicki SPA, Prosciak MP, Gerlach AT, et al. Atrial fibrillation after esophagectomy: an indicator of postoperative morbidity. Gen Thorac Cardiovasc Surg, 2011, 59(6): 399-405.
36. Murthy SC, Law S, Whooley BP, et al. Atrial fibrillation after esophagectomy is a marker for postoperative morbidity and mortality. J Thorac Cardiovasc Surg, 2003, 126(4): 1162-1167.
37. Stippel DL, Taylan C, Schröder W, et al. Supraventricular tachyarrhythmia as early indicator of a complicated course after esophagectomy. Dis Esophagus, 2005, 18(4): 267-273.
38. Walsh SR, Tang T, Wijewardena C, et al. Postoperative arrhythmias in general surgical patients. Ann R Coll Surg Engl, 2007, 89(2): 91-95.
39. Cardinale D, Sandri MT, Colombo A, et al. Prevention of atrial fibrillation in high-risk patients undergoing lung cancer surgery: the PRESAGE trial. Ann Surg, 2016, 264(2): 244-251.
40. Bayliff CD, Massel DR, Inculet RI, et al. Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. Ann Thorac Surg, 1999, 67(1): 182-186.
41. Ojima T, Nakamori M, Nakamura M, et al. Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer. Br J Surg, 2017, 104(8): 1003-1009.
42. Tisdale JE, Wroblewski HA, Wall DS, et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. J Thorac Cardiovasc Surg, 2010, 140(1): 45-51.
43. Amar D, Zhang H, Chung MK, et al. Amiodarone with or without N-acetylcysteine for the prevention of atrial fibrillation after thoracic surgery: a double-blind, randomized trial. Anesthesiology, 2022, 136(6): 916-926.
44. Tisdale JE, Jaynes HA, Watson MR, et al. Amiodarone for prevention of atrial fibrillation following esophagectomy. J Thorac Cardiovasc Surg, 2019, 158(1): 301-310. e1.
45. Tisdale JE, Wroblewski HA, Kesler KA. Prophylaxis of atrial fibrillation after noncardiac thoracic surgery. Semin Thorac Cardiovasc Surg, 2010, 22(4): 310-320.

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