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Published in: Heart and Vessels 5/2021

01-05-2021 | Atrial Fibrillation | Original Article

Serum human epididymis protein 4 levels in the prediction of the recurrence of atrial fibrillation after catheter ablation

Authors: Zhi-Jie Mao, Ya Lin, Xiao-Kang Hu, Yi-He Chen, Wei-jian Huang, Zhou-Qing Huang

Published in: Heart and Vessels | Issue 5/2021

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Abstract

The aim of this study is to assess serum human epididymis protein 4 (HE-4) levels as a biomarker for predicting the recurrence of atrial fibrillation (AF) after catheter ablation. This was a prospective observational study that enrolled one hundred eighty-four consecutive nonvalvular AF patients (65 persistent, 119 paroxysmal) who were eligible for their first ablation. Multiple Cox proportional hazards models and Kaplan–Meier curve analyses were used to test the association between serum HE-4 levels and AF recurrence after catheter ablation. During the 12-month follow-up, we observed that 47 patients (25.5%) experienced AF recurrence. Patients were divided into tertiles of HE-4 level (T1: < 50 pmol/L; T2: ≥ 50 pmol/L). The AF recurrence rate of higher serum HE-4 level patients was significantly increased (34.6% vs 13.8%, P < 0.001). Generalized additive models were used to visually assess functional relationships between the serum HE-4 levels and the risk of AF recurrence. When stratified with serum levels as the cut-off value, Kaplan–Meier analysis showed that patients with serum HE-4 levels (> 50 pmol/L) had a significantly increased risk of AF recurrence. In addition, multivariate Cox proportional hazard modelling revealed that HE-4 (≥ 50 pmol/L) (HR 2.65; 95% CI 1.34, 5.27, P = 0.005) was independent predictors of AF recurrence. Serum HE-4 levels in patients with AF are associated with postoperative recurrence of AF, and high HE-4 levels are an independent predictor of AF recurrence after ablation.
Literature
1.
go back to reference Piccini JP, Hammill BG, Sinner MF, Hernandez AF, Walkey AJ, Benjamin EJ, Curtis LH, Heckbert SR (2014) Clinical course of atrial fibrillation in older adults: the importance of cardiovascular events beyond stroke. Eur Heart J 35:250–256CrossRef Piccini JP, Hammill BG, Sinner MF, Hernandez AF, Walkey AJ, Benjamin EJ, Curtis LH, Heckbert SR (2014) Clinical course of atrial fibrillation in older adults: the importance of cardiovascular events beyond stroke. Eur Heart J 35:250–256CrossRef
2.
go back to reference Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D’Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ (2004) Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110:1042–1046CrossRef Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D’Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ (2004) Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110:1042–1046CrossRef
3.
go back to reference Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Kokturk B, Konstantinidou M, Metzner A, Fuernkranz A, Kuck KH (2010) Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation 122:2368–2377CrossRef Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Kokturk B, Konstantinidou M, Metzner A, Fuernkranz A, Kuck KH (2010) Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation 122:2368–2377CrossRef
4.
go back to reference Weerasooriya R, Khairy P, Litalien J, Macle L, Hocini M, Sacher F, Lellouche N, Knecht S, Wright M, Nault I, Miyazaki S, Scavee C, Clementy J, Haissaguerre M, Jais P (2011) Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 57:160–166CrossRef Weerasooriya R, Khairy P, Litalien J, Macle L, Hocini M, Sacher F, Lellouche N, Knecht S, Wright M, Nault I, Miyazaki S, Scavee C, Clementy J, Haissaguerre M, Jais P (2011) Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 57:160–166CrossRef
5.
go back to reference Chelu MG, King JB, Kholmovski EG, Ma J, Gal P, Marashly Q, AlJuaid MA, Kaur G, Silver MA, Johnson KA, Suksaranjit P, Wilson BD, Han FT, Elvan A, Marrouche NF (2018) Atrial fibrosis by late gadolinium enhancement magnetic resonance imaging and catheter ablation of atrial fibrillation: 5-year follow-up data. J Am Heart Assoc 7:e006313CrossRef Chelu MG, King JB, Kholmovski EG, Ma J, Gal P, Marashly Q, AlJuaid MA, Kaur G, Silver MA, Johnson KA, Suksaranjit P, Wilson BD, Han FT, Elvan A, Marrouche NF (2018) Atrial fibrosis by late gadolinium enhancement magnetic resonance imaging and catheter ablation of atrial fibrillation: 5-year follow-up data. J Am Heart Assoc 7:e006313CrossRef
6.
go back to reference Sohns C, Marrouche NF (2020) Atrial fibrillation and cardiac fibrosis. Eur Heart J 41:1123–1131CrossRef Sohns C, Marrouche NF (2020) Atrial fibrillation and cardiac fibrosis. Eur Heart J 41:1123–1131CrossRef
7.
go back to reference LeBleu VS, Teng Y, O’Connell JT, Charytan D, Muller GA, Muller CA, Sugimoto H, Kalluri R (2013) Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nat Med 19:227–231CrossRef LeBleu VS, Teng Y, O’Connell JT, Charytan D, Muller GA, Muller CA, Sugimoto H, Kalluri R (2013) Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nat Med 19:227–231CrossRef
8.
go back to reference Luo J, Wang F, Wan J, Ye Z, Huang C, Cai Y, Liu M, Wu BQ, Li L (2018) Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients. Clin Chim Acta 483:216–221CrossRef Luo J, Wang F, Wan J, Ye Z, Huang C, Cai Y, Liu M, Wu BQ, Li L (2018) Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients. Clin Chim Acta 483:216–221CrossRef
9.
go back to reference Zhang M, Yuan L, Yao F, Cao P, Rong J, Zhang B, Su J (2018) Human epididymis protein 4 concentration is not associated with liver fibrosis and cirrhosis in a case control study. Clin Chim Acta 484:213–217CrossRef Zhang M, Yuan L, Yao F, Cao P, Rong J, Zhang B, Su J (2018) Human epididymis protein 4 concentration is not associated with liver fibrosis and cirrhosis in a case control study. Clin Chim Acta 484:213–217CrossRef
10.
go back to reference de Boer RA, Cao Q, Postmus D, Damman K, Voors AA, Jaarsma T, van Veldhuisen DJ, Arnold WD, Hillege HL, Sillje HH (2013) The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure. JACC Heart Fail 1:164–169CrossRef de Boer RA, Cao Q, Postmus D, Damman K, Voors AA, Jaarsma T, van Veldhuisen DJ, Arnold WD, Hillege HL, Sillje HH (2013) The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure. JACC Heart Fail 1:164–169CrossRef
11.
go back to reference Piek A, Meijers WC, Schroten NF, Gansevoort RT, de Boer RA, Sillje HH (2017) HE4 serum levels are associated with heart failure severity in patients with chronic heart failure. J Card Fail 23:12–19CrossRef Piek A, Meijers WC, Schroten NF, Gansevoort RT, de Boer RA, Sillje HH (2017) HE4 serum levels are associated with heart failure severity in patients with chronic heart failure. J Card Fail 23:12–19CrossRef
12.
go back to reference Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, ESC Scientific Document Group (2016) ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962. https://doi.org/10.1093/eurheartj/ehw210CrossRefPubMed Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, ESC Scientific Document Group (2016) ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962. https://​doi.​org/​10.​1093/​eurheartj/​ehw210CrossRefPubMed
13.
go back to reference Bertaglia E, Senatore G, De Michieli L, De Simone A, Amellone C, Ferretto S, La Rocca V, Giuggia M, Corrado D, Zoppo F, Stabile G (2017) Twelve-year follow-up of catheter ablation for atrial fibrillation: A prospective, multicenter, randomized study. Heart Rhythm 14:486–492CrossRef Bertaglia E, Senatore G, De Michieli L, De Simone A, Amellone C, Ferretto S, La Rocca V, Giuggia M, Corrado D, Zoppo F, Stabile G (2017) Twelve-year follow-up of catheter ablation for atrial fibrillation: A prospective, multicenter, randomized study. Heart Rhythm 14:486–492CrossRef
14.
go back to reference Njoku A, Kannabhiran M, Arora R, Reddy P, Gopinathannair R, Lakkireddy D, Dominic P (2018) Left atrial volume predicts atrial fibrillation recurrence after radiofrequency ablation: a meta-analysis. Europace 20:33–42CrossRef Njoku A, Kannabhiran M, Arora R, Reddy P, Gopinathannair R, Lakkireddy D, Dominic P (2018) Left atrial volume predicts atrial fibrillation recurrence after radiofrequency ablation: a meta-analysis. Europace 20:33–42CrossRef
15.
go back to reference Hussein AA, Saliba WI, Martin DO, Shadman M, Kanj M, Bhargava M, Dresing T, Chung M, Callahan T, Baranowski B, Tchou P, Lindsay BD, Natale A, Wazni OM (2011) Plasma B-type natriuretic peptide levels and recurrent arrhythmia after successful ablation of lone atrial fibrillation. Circulation 123:2077–2082CrossRef Hussein AA, Saliba WI, Martin DO, Shadman M, Kanj M, Bhargava M, Dresing T, Chung M, Callahan T, Baranowski B, Tchou P, Lindsay BD, Natale A, Wazni OM (2011) Plasma B-type natriuretic peptide levels and recurrent arrhythmia after successful ablation of lone atrial fibrillation. Circulation 123:2077–2082CrossRef
16.
go back to reference Jiang Q, Chen Z, Yang L (2020) Association of over 3-year duration with recurrence after catheter ablation in patients with persistent atrial fibrillation. J Cardiovasc Electrophysiol 31:753CrossRef Jiang Q, Chen Z, Yang L (2020) Association of over 3-year duration with recurrence after catheter ablation in patients with persistent atrial fibrillation. J Cardiovasc Electrophysiol 31:753CrossRef
17.
go back to reference Yu HT, Kim IS, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN (2020) Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation. J Cardiovasc Electrophysiol 31:457–464CrossRef Yu HT, Kim IS, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN (2020) Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation. J Cardiovasc Electrophysiol 31:457–464CrossRef
18.
go back to reference Ricciardi D, Arena G, Verlato R, Iacopino S, Pieragnoli P, Molon G, Manfrin M, Allocca G, Cattafi G, Sirico G, Rovaris G, Sciarra L, Nicolis D, Tondo C (2019) Sex effect on efficacy of pulmonary vein cryoablation in patients with atrial fibrillation: data from the multicenter real-world 1STOP project. J Interv Card Electrophysiol 56:9–18CrossRef Ricciardi D, Arena G, Verlato R, Iacopino S, Pieragnoli P, Molon G, Manfrin M, Allocca G, Cattafi G, Sirico G, Rovaris G, Sciarra L, Nicolis D, Tondo C (2019) Sex effect on efficacy of pulmonary vein cryoablation in patients with atrial fibrillation: data from the multicenter real-world 1STOP project. J Interv Card Electrophysiol 56:9–18CrossRef
19.
go back to reference Allam L, Samir R, Ali AN (2019) Clinical outcomes of catheter ablation of paroxysmal atrial fibrillation in very young population compared to older population: a prospective study. Egypt Heart J 71:11CrossRef Allam L, Samir R, Ali AN (2019) Clinical outcomes of catheter ablation of paroxysmal atrial fibrillation in very young population compared to older population: a prospective study. Egypt Heart J 71:11CrossRef
20.
go back to reference Wang M, Tellor KB, Ramaswamy K, Krainik AJ, Armbruster AL (2019) Evaluation of the effect of prior antiarrhythmic drug use on the success of atrial fibrillation catheter ablation. J Clin Pharm Ther 44:708–714CrossRef Wang M, Tellor KB, Ramaswamy K, Krainik AJ, Armbruster AL (2019) Evaluation of the effect of prior antiarrhythmic drug use on the success of atrial fibrillation catheter ablation. J Clin Pharm Ther 44:708–714CrossRef
21.
go back to reference Yao Y, Yao W, Bai R, Lu ZH, Tang RB, Long DY, Jiang CX, Sang CH, Zhang JQ, Yu RH, Du X, Liu XH, Dong JZ, Ma CS (2017) Plasma homocysteine levels predict early recurrence after catheter ablation of persistent atrial fibrillation. Europace 19:66–71PubMed Yao Y, Yao W, Bai R, Lu ZH, Tang RB, Long DY, Jiang CX, Sang CH, Zhang JQ, Yu RH, Du X, Liu XH, Dong JZ, Ma CS (2017) Plasma homocysteine levels predict early recurrence after catheter ablation of persistent atrial fibrillation. Europace 19:66–71PubMed
22.
go back to reference Winkle RA, Jarman JW, Mead RH, Engel G, Kong MH, Fleming W, Patrawala RA (2016) Predicting atrial fibrillation ablation outcome: the CAAP-AF score. Heart Rhythm 13:2119–2125CrossRef Winkle RA, Jarman JW, Mead RH, Engel G, Kong MH, Fleming W, Patrawala RA (2016) Predicting atrial fibrillation ablation outcome: the CAAP-AF score. Heart Rhythm 13:2119–2125CrossRef
23.
go back to reference Kornej J, Hindricks G, Shoemaker MB, Husser D, Arya A, Sommer P, Rolf S, Saavedra P, Kanagasundram A, Patrick Whalen S, Montgomery J, Ellis CR, Darbar D, Bollmann A (2015) The APPLE score: a novel and simple score for the prediction of rhythm outcomes after catheter ablation of atrial fibrillation. Clin Res Cardiol 104:871–876CrossRef Kornej J, Hindricks G, Shoemaker MB, Husser D, Arya A, Sommer P, Rolf S, Saavedra P, Kanagasundram A, Patrick Whalen S, Montgomery J, Ellis CR, Darbar D, Bollmann A (2015) The APPLE score: a novel and simple score for the prediction of rhythm outcomes after catheter ablation of atrial fibrillation. Clin Res Cardiol 104:871–876CrossRef
24.
go back to reference Deng H, Shantsila A, Xue Y, Potpara TS, Bai Y, Zhan X, Fang X, Liao H, Wei W, Wu S, Lip GYH (2018) Using the MB-LATER score for predicting arrhythmia outcome after catheter ablation for atrial fibrillation: the Guangzhou atrial fibrillation project. Int J Clin Pract 72:e13247CrossRef Deng H, Shantsila A, Xue Y, Potpara TS, Bai Y, Zhan X, Fang X, Liao H, Wei W, Wu S, Lip GYH (2018) Using the MB-LATER score for predicting arrhythmia outcome after catheter ablation for atrial fibrillation: the Guangzhou atrial fibrillation project. Int J Clin Pract 72:e13247CrossRef
25.
go back to reference Black-Maier E, Parish A, Steinberg BA, Green CL, Loring Z, Barnett AS, Al-Khatib SM, Atwater BD, Daubert JP, Frazier-Mills C, Hegland DD, Jackson KP, Jackson LR, Koontz J, Lewis RK, Pokorney SD, Sun AY, Thomas KL, Bahnson TD, Piccini JP (2019) Predicting atrial fibrillation recurrence after ablation in patients with heart failure: validity of the APPLE and CAAP-AF risk scoring systems. Pacing Clin Electrophysiol 42:1440–1447CrossRef Black-Maier E, Parish A, Steinberg BA, Green CL, Loring Z, Barnett AS, Al-Khatib SM, Atwater BD, Daubert JP, Frazier-Mills C, Hegland DD, Jackson KP, Jackson LR, Koontz J, Lewis RK, Pokorney SD, Sun AY, Thomas KL, Bahnson TD, Piccini JP (2019) Predicting atrial fibrillation recurrence after ablation in patients with heart failure: validity of the APPLE and CAAP-AF risk scoring systems. Pacing Clin Electrophysiol 42:1440–1447CrossRef
26.
go back to reference D’Ascenzo F, Corleto A, Biondi-Zoccai G, Anselmino M, Ferraris F, di Biase L, Natale A, Hunter RJ, Schilling RJ, Miyazaki S, Tada H, Aonuma K, Yenn-Jiang L, Tao H, Ma C, Packer D, Hammill S, Gaita F (2013) Which are the most reliable predictors of recurrence of atrial fibrillation after transcatheter ablation? A meta-analysis. Int J Cardiol 167:1984–1989CrossRef D’Ascenzo F, Corleto A, Biondi-Zoccai G, Anselmino M, Ferraris F, di Biase L, Natale A, Hunter RJ, Schilling RJ, Miyazaki S, Tada H, Aonuma K, Yenn-Jiang L, Tao H, Ma C, Packer D, Hammill S, Gaita F (2013) Which are the most reliable predictors of recurrence of atrial fibrillation after transcatheter ablation? A meta-analysis. Int J Cardiol 167:1984–1989CrossRef
27.
go back to reference Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, Jiang SW (2009) HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 9:555–566CrossRef Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, Jiang SW (2009) HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 9:555–566CrossRef
28.
go back to reference Huang Y, Jiang H, Zhu L (2020) Human epididymis protein 4 as an indicator of acute heart failure in patients with chronic kidney disease. Lab Med 51:169–175PubMed Huang Y, Jiang H, Zhu L (2020) Human epididymis protein 4 as an indicator of acute heart failure in patients with chronic kidney disease. Lab Med 51:169–175PubMed
Metadata
Title
Serum human epididymis protein 4 levels in the prediction of the recurrence of atrial fibrillation after catheter ablation
Authors
Zhi-Jie Mao
Ya Lin
Xiao-Kang Hu
Yi-He Chen
Wei-jian Huang
Zhou-Qing Huang
Publication date
01-05-2021
Publisher
Springer Japan
Published in
Heart and Vessels / Issue 5/2021
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-020-01744-4

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