Serum Homocysteine and Atrial Fibrillation Recurrence after Catheter Ablation: A Meta-Analysis of 11 Cohort Studies Involving 2147 Patients

Abstract

The relationship between serum homocysteine (Hcy) levels and atrial fibrillation (AF) recurrence following catheter ablation remains unclear. This meta-analysis aims to investigate this association. Comprehensive searches in PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases identified relevant studies published up to May 25, 2024. Cohort studies that measured pre-ablation serum Hcy levels and reported AF recurrence post-ablation were included. Data were analyzed using random-effects models by incorporating the potential influence of heterogeneity, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated for the association between serum Hcy levels and AF recurrence. Eleven retrospective cohort studies involving 2147 patients with AF who underwent catheter ablation were analyzed. Higher pre-ablation serum Hcy levels were associated with an increased risk of AF recurrence (OR for per 1 μmol/l increment of Hcy: 1.22, 95% CI: 1.17 to 1.28, p<0.001; I²=0%). Additionally, studies that categorized Hcy levels also found a higher risk of AF recurrence in patients with elevated Hcy (OR for patients with a high versus a low serum Hcy: 2.75, 95% CI: 2.02 to 3.75, p <0.001; I²=0%). Funnel plots and Egger’s regression test indicated low risks of publication bias. In conclusions, elevated pre-ablation serum Hcy levels are significantly associated with an increased risk of AF recurrence post-catheter ablation. These findings suggest that Hcy could be a valuable biomarker for predicting AF recurrence and may inform pre-ablation risk stratification. Further prospective studies are warranted to confirm these results.

Keywords

homocysteine - atrial fibrillation - catheter ablation - recurrence - meta-analysis

Publication History

Received: 18 July 2024

Accepted after revision: 23 October 2024

Article published online:
22 November 2024

• References

• 1 Dong XJ, Wang BB, Hou FF. et al. Global burden of atrial fibrillation/atrial flutter and its attributable risk factors from 1990 to 2019. Europace 2023; 25: 793-803
• 2 Martin SS, Aday AW, Almarzooq ZI. et al. 2024 Heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation 2024; 149: e347-e913
• 3 Elliott AD, Middeldorp ME, Van Gelder IC. et al. Epidemiology and modifiable risk factors for atrial fibrillation. Nat Rev Cardiol 2023; 20: 404-417
• 4 Brundel B, Ai X, Hills MT. et al. Atrial fibrillation. Nat Rev Dis Primers 2022; 8: 21
• 5 Walsh K, Marchlinski F. Catheter ablation for atrial fibrillation: current patient selection and outcomes. Expert Rev Cardiovasc Ther 2018; 16: 679-692
• 6 Parameswaran R, Al-Kaisey AM, Kalman JM. Catheter ablation for atrial fibrillation: current indications and evolving technologies. Nat Rev Cardiol 2021; 18: 210-225
• 7 Erhard N, Metzner A, Fink T. Late arrhythmia recurrence after atrial fibrillation ablation: incidence, mechanisms and clinical implications. Herzschrittmacherther Elektrophysiol 2022; 33: 71-76
• 8 Gaztanaga L, Frankel DS, Kohari M. et al. Time to recurrence of atrial fibrillation influences outcome following catheter ablation. Heart Rhythm 2013; 10: 2-9
• 9 Nedios S, Lindemann F, Heijman J. et al. Atrial remodeling and atrial fibrillation recurrence after catheter ablation: past, present, and future developments. Herz 2021; 46: 312-317
• 10 Mohanty S, Della Rocca DG, Gianni C. et al. Predictors of recurrent atrial fibrillation following catheter ablation. Expert Rev Cardiovasc Ther 2021; 19: 237-246
• 11 Ivanov V, Smereka Y, Rasputin V. et al. Homocysteine and atrial fibrillation: novel evidences and insights. Monaldi Arch Chest Dis 2022; 93
• 12 Gospodarczyk A, Marczewski K, Gospodarczyk N. et al. Homocysteine and cardiovascular disease – a current review. Wiad Lek 2022; 75: 2862-2866
• 13 Yuan D, Chu J, Lin H. et al. Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis. Front Cardiovasc Med 2022; 9: 1109445
• 14 Yao Y, Shang MS, Dong JZ. et al. Homocysteine in non-valvular atrial fibrillation: role and clinical implications. Clin Chim Acta 2017; 475: 85-90
• 15 Pacher P, Ungvari Z, Kecskemeti V. Electrophysiological effects of homocysteine in isolated rat right ventricular papillary muscles and left atria. Gen Pharmacol 1999; 32: 439-443
• 16 Cai BZ, Gong DM, Liu Y. et al. Homocysteine inhibits potassium channels in human atrial myocytes. Clin Exp Pharmacol Physiol 2007; 34: 851-855
• 17 Kubota Y, Alonso A, Heckbert SR. et al. Homocysteine and incident atrial fibrillation: the atherosclerosis risk in communities study and the multi-ethnic study of atherosclerosis. Heart Lung Circ 2019; 28: 615-622
• 18 Sun X, Lu Y, Wang Z. et al. No causal association between plasma homocysteine levels and atrial fibrillation: a Mendelian randomization study. Nutr Metab Cardiovasc Dis 2021; 31: 587-591
• 19 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
• 20 Page MJ, Moher D, Bossuyt PM. et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160
• 21 Higgins J, Thomas J, Chandler J. et al. Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. 2021 www.training.cochrane.org/handbook
• 22 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
• 23 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
• 24 Li GL, Jiang H, Li JX. et al. Correlation of high-sensitivity C-reactive protein and homocysteine levels with recurrence of paroxysmal atrial fibrillation after catheter ablation. Chin J Cardiac Arrtyth 2015; 19: 118-120
• 25 Zhou L, Tang SP. The effect of plasma homocysteine levels on recurrence of paroxysmal atrial fibrillation after catheter ablation. Anhui Med Pharmacol J 2015; 19: 922-924
• 26 Snezhitsky VA, Yatskevich ES, Doroshenko EM. et al. Homocysteine as a prognostic marker of atrial remodeling and clinical picture in patients with paroxysmal and persistent forms of atrial fibrillation. Klin Med (Mosk) 2016; 94: 16-22
• 27 Yao Y, Yao W, Bai R. et al. Plasma homocysteine levels predict early recurrence after catheter ablation of persistent atrial fibrillation. Europace 2017; 19: 66-71
• 28 Xie DJ, Zhou JH, Yuan XY. et al. Risk factors for recurrence of atrial fibrillation after first radiofrequency ablation. Jilin Med J 2019; 40: 950-954
• 29 Huang MH, Sun YZ. Correlation between plasma myeloperoxidase levels and recurrence after radiofrequency ablation in patients with atrial fibrillation. Lab Med Clin 2020; 17: 1698-1701
• 30 Xie L, Tuo W, Fu H. Predictive value of serum homocysteine and brain natriuretic peptide levels for recurrence of patients with atrial fibrillation after radiofrequency ablation. J Clin Pathol Res 2020; 40: 2295-2301
• 31 Chen WG, Zhang SY, Gu YF. et al. Correlation between Hcy, ejection fraction, left atrial volume index and AF recurrence after radiofrequency ablation. Chin. J Evid Based Cardiovasc Med 2021; 13: 421-424
• 32 Cao ZF, He M, Wang XP. et al. Prediction of recurrence of atrial fibrillation after radiofrequency ablation using body mass index combined with inflammatory markers. J Med Ther Pract 2022; 35: 2989-2991
• 33 Xu JP, Ma XF, Wang H. et al. Predictive value of RDW combined with Hcy in the recurrence of atrial fibrillation after radiofrequency ablation. Chin Med Herald 2022; 19: 66-69
• 34 Zhang X, Chen Y, Lou L. et al. Medical economic consequences, predictors, and outcomes of immediate atrial fibrillation recurrence after radiofrequency ablation. Cardiovasc Innov Appl 2024; 9: e958
• 35 Charalampidis P, Teperikidis E, Boulmpou A. et al. Homocysteine as a predictor of paroxysmal atrial fibrillation-related events: a scoping review of the literature. Diagnostics (Basel) 2022; 12: 2192
• 36 Richter B, Gwechenberger M, Socas A. et al. Markers of oxidative stress after ablation of atrial fibrillation are associated with inflammation, delivered radiofrequency energy and early recurrence of atrial fibrillation. Clin Res Cardiol 2012; 101: 217-225
• 37 Shimano M, Inden Y, Tsuji Y. et al. Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation. Europace 2008; 10: 961-966
• 38 Matsuzawa Y, Suleiman M, Guddeti RR. et al. Age-dependent predictive value of endothelial dysfunction for arrhythmia recurrence following pulmonary vein isolation. J Am Heart Assoc 2016; 5: e 003183
• 39 Cai B, Shan L, Gong D. et al. Homocysteine modulates sodium channel currents in human atrial myocytes. Toxicology 2009; 256: 201-206
• 40 Han L, Dong QB, Wei YC. et al. [Homocysteine induces calcium overload in neonatal rat atrial cells through activation of sodium current and CaMKIIdelta]. Zhonghua Xin Xue Guan Bing Za Zhi 2018; 46: 143-151
• 41 Han L, Wu A, Li Q. et al. Homocysteine-induced electrical remodeling via the mediation of IP(3)R1/Nav1.5 signaling pathway. Am J Transl Res 2020; 12: 3822-3841
• 42 Raniga D, Goda M, Hattingh L. et al. Left atrial volume index: a predictor of atrial fibrillation recurrence following direct current cardioversion – a systematic review and meta-analysis. Int J Cardiol Heart Vasc 2024; 51: 101364
• 43 Balk EM, Garlitski AC, Alsheikh-Ali AA. et al. Predictors of atrial fibrillation recurrence after radiofrequency catheter ablation: a systematic review. J Cardiovasc Electrophysiol 2010; 21: 1208-1216
• 44 Jiang Z, Dai L, Song Z. et al. Association between C-reactive protein and atrial fibrillation recurrence after catheter ablation: a meta-analysis. Clin Cardiol 2013; 36: 548-554
• 45 Dong Y, Huang T, Zhai Z. et al. Lowering serum homocysteine in H-type hypertensive patients with atrial fibrillation after radiofrequency catheter ablation to prevent atrial fibrillation recurrence. Front Nutr 2022; 9: 995838