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

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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.

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References

  1. 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 35:250–256

    Article  Google Scholar 

  2. 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 110:1042–1046

    Article  Google Scholar 

  3. 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 122:2368–2377

    Article  Google Scholar 

  4. 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 57:160–166

    Article  Google Scholar 

  5. 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:e006313

    Article  CAS  Google Scholar 

  6. Sohns C, Marrouche NF (2020) Atrial fibrillation and cardiac fibrosis. Eur Heart J 41:1123–1131

    Article  CAS  Google Scholar 

  7. 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 19:227–231

    Article  CAS  Google Scholar 

  8. 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 483:216–221

    Article  CAS  Google Scholar 

  9. 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 484:213–217

    Article  CAS  Google Scholar 

  10. 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 1:164–169

    Article  Google Scholar 

  11. 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 23:12–19

    Article  CAS  Google Scholar 

  12. 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/ehw210

    Article  PubMed  Google Scholar 

  13. 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 14:486–492

    Article  Google Scholar 

  14. 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 20:33–42

    Article  Google Scholar 

  15. 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 123:2077–2082

    Article  CAS  Google Scholar 

  16. 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 31:753

    Article  Google Scholar 

  17. 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 31:457–464

    Article  Google Scholar 

  18. 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 56:9–18

    Article  Google Scholar 

  19. 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 71:11

    Article  Google Scholar 

  20. 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 44:708–714

    Article  CAS  Google Scholar 

  21. 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 19:66–71

    PubMed  Google Scholar 

  22. 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 13:2119–2125

    Article  Google Scholar 

  23. 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 104:871–876

    Article  Google Scholar 

  24. 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:e13247

    Article  Google Scholar 

  25. 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 42:1440–1447

    Article  Google Scholar 

  26. 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 167:1984–1989

    Article  CAS  Google Scholar 

  27. 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 9:555–566

    Article  CAS  Google Scholar 

  28. 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 51:169–175

    PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (Grant no. 81670227) and the Wenzhou Science and Technology Bureau (Grant no. Y20180099).

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Correspondence to Wei-jian Huang or Zhou-Qing Huang.

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Mao, ZJ., Lin, Y., Hu, XK. et al. Serum human epididymis protein 4 levels in the prediction of the recurrence of atrial fibrillation after catheter ablation. Heart Vessels 36, 686–692 (2021). https://doi.org/10.1007/s00380-020-01744-4

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