Abstract

Background: This study aims to evaluate the long-term rhythm outcomes of the Cox-Maze IV procedure in patients undergoing complex cardiac surgery, where atrial fibrillation ablation was performed as a second, third, or fourth-and-beyond concomitant operation.

Methods: Between October 2018 and February 2025, a total of 71 patients (24 males, 47 females; mean age: 59±10 years; range, 36 to 80 years) who underwent a complete Cox-Maze IV lesion set and achieved at least six months of rhythm follow-up were retrospectively analyzed. The patients were grouped by the number of concomitant cardiac procedures performed: Group 1 (one procedure, n=16), Group 2 (two procedures, n=43), and Group 3 (?3 procedures, n=12). Rhythm monitoring included 24-h Holter and pacemaker interrogation.

Results: At a mean follow-up of 26±2 months, overall freedom rate from atrial tachyarrhythmias was 88.7%. Group-specific freedom rate from atrial tachyarrhythmias at 36 months was as follows: 100% in Group 1, 80.0% in Group 2, and 87.5% in Group 3. No significant intergroup differences were observed. Pacemaker implantation was needed in 7.0% of the patients. Higher procedural complexity did not adversely affect rhythm outcomes.

Conclusion: Our study results suggest that Cox-Maze IV provides excellent long-term rhythm control even in complex cardiac surgeries involving multiple concomitant procedures. The effectiveness of the procedure appears to be preserved across increasing surgical complexity, supporting its broader application.

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients undergoing cardiac surgery, and its presence is associated with increased morbidity, stroke risk, and long-term mortality.[1,2] Recognizing its clinical significance, both American and European guidelines strongly recommend surgical ablation for AF in patients undergoing concomitant mitral valve (MV), aortic valve (AV), and/or coronary artery bypass grafting (CABG) surgery (Class I, Level A recommendation).[2-4]

The Cox-Maze IV (CM-IV) procedure has emerged as the gold standard for the surgical treatment of AF, offering consistent long-term success across a range of primary cardiac operations.[5,6] Reported freedom from atrial tachyarrhythmias (ATAs) exceeds 75% at five to 10 years, with significant reductions in stroke risk and mortality.[7,8] Despite this, real-world utilization of surgical ablation remains low in both the United States and Europe.[9,10] Large-scale registry studies suggest that fewer than 10% of eligible patients receive surgical AF ablation during cardiac surgery, revealing a disconnect between guideline recommendations and clinical practice.[11,12]

Current guidelines and published outcomes primarily address AF as a secondary indication in patients undergoing one or two concomitant procedures (e.g., MV surgery alone or combined with tricuspid valve repair or CABG).[13,14] However, in developing regions, patients frequently require multiple simultaneous cardiac procedures due to late presentation or advanced rheumatic heart disease. In these cases, AF often becomes a tertiary, quaternary, or even quinary indication. Yet, long-term outcomes of CM-IV in such complex surgical contexts still remain underreported.

This lack of robust outcome data may deter surgeons from performing CM-IV in high-complexity settings, where concerns about prolonged operative time, elevated surgical risk, and uncertain rhythm outcomes may prevail. In the present study, we aimed to evaluate the long-term outcomes of CM-IV in patients undergoing cardiac surgery in which AF ablation was performed as the second, third, or fourth-and-beyond procedure. By stratifying patients according to procedural complexity, we aimed to determine whether CM-IV could maintain its efficacy in increasingly complex surgical settings.

Methods

This single-center, retrospective cohort study was conducted at Koşuyolu Yüksek İhtisas Training and Research Hospital, Department of Cardiovascular Surgery between October 30th, 2018 and February 15th, 2025 a total of 104 patients underwent surgical ablation for AF. Of these, 81 (77.9%) patients received a complete CM-IV lesion set. All procedures were performed by the principal investigator who received formal CM-IV training. Patients with incomplete lesion sets (n=23; 17 box lesions only, 6 pulmonary vein isolation ± right atrial lesions) were excluded. Additionally, five in-hospital mortalities were excluded, with causes including vasoplegia (n=2), mesenteric ischemia (n=1), sepsis (n=1), and right heart failure with hemorrhagic shock (n=1). Another five patients were within the three-month blanking period at analysis time. Finally, a total of 71 patients (24 males, 47 females; mean age: 59±10 years; range, 36 to 80 years) who received complete CM-IV with a ?6-month follow-up were included. Written informed consent was obtained from each patient. The study protocol was approved by the Koşuyolu High Specialization Training and Research Hospital Scientific Research Ethics Committee (Date: 22.04.2025, No: 2025/06/1091). The study was conducted in accordance with the principles of the Declaration of Helsinki.

The patients were stratified into three groups based on the number of concomitant cardiac procedures performed alongside the CM-IV procedure. Group 1 (n=16) consisted of patients who underwent CM-IV in combination with one additional procedure. Group 2 (n=43) included those who had two concomitant procedures, while Group 3 (n=12) comprised patients who underwent CM-IV along with three or more additional cardiac procedures.

Surgical approach and lesion set
All CM-IV procedures were performed via median sternotomy, utilizing bipolar radiofrequency and/or cryoablation energy sources in accordance with the original technique described by Damiano et al.[15] The lesion set included bilateral pulmonary vein isolation, followed by a connecting box lesion to electrically isolate the posterior left atrium. A mitral isthmus line was done by cryo-energy to complete left atrial lesion sets. In addition, right atrial lesions extending to the tricuspid annulus were applied.

Follow-up and rhythm monitoring
Follow-up evaluations were conducted in accordance with the protocol described by Weimar et al.[16] Patients underwent scheduled rhythm assessments at three, six, and 12 months after surgery, followed by annual evaluations. At each visit, a standard 12-lead electrocardiogram (ECG) was performed. When sinus rhythm was detected, a 24-h Holter monitoring or pacemaker interrogation was also utilized to detect any possible arrhythmia episodes. Sinus rhythm and recurrence of ATAs were assessed according to the guidelines of the Heart Rhythm Society.[17] Atrial tachyarrhythmias recurrence was defined as any documented episode of AF, atrial flutter, or atrial tachycardia lasting 30 sec or longer, detected beyond the three-month postoperative blanking period, by any available monitoring method, including Holter monitoring or pacemaker interrogation. Additionally, patients" anticoagulation status and any thromboembolic complications encountered during follow-up were recorded.

Statistical analysis
Statistical analysis was performed using the R Studio version 4.3.1 software (R Studio, PBC, Boston, MA, USA). The following R packages were utilized: 'tidyverse' for data processing and visualization, 'survival' and 'survminer' for Kaplan-Meier analysis, and 'ggplot2' for graphical representation. Continuous variables were expressed in mean ± standard deviation (SD) for normally distributed data or median with interquartile range (IQR) for non-normally distributed data. Categorical variables were expressed in number and frequency. Normality was assessed using the Shapiro-Wilk test and visual inspection of Q-Q plots. Comparisons of continuous variables across groups (e.g., cross-clamp time, cardiopulmonary bypass [CPB] time) were performed using one-way analysis of variance (ANOVA) when assumptions were met; otherwise, the Kruskal-Wallis test was used. Post-hoc pairwise comparisons were adjusted using Bonferroni correction. Categorical variables were analyzed using the chi-square test or Fisher exact test, as appropriate. Time-to-event data for rhythm recurrence defined as any ATA lasting ≥30 sec beyond the three-month blanking period were analyzed using the Kaplan-Meier method, and group differences were assessed with the log-rank test. Patients without recurrence were censored at the last known follow-up. A two-sided p value of <0.05 was considered statistically significant.

Results

Most individuals had long-standing persistent AF, accounting for 91.5% of the cohort. The mean left atrial diameter was 4.8±0.6 cm, and the mean left ventricular ejection fraction (LVEF) was 58±9% (Table 1). Detailed operative data for all groups are presented in Table 2.

Table 1. Baseline demographic and clinical characteristics of the study population

Table 2. Details of the concomitant operations

As expected, operative times increased with the number of procedures performed. Group 1 had a mean aortic cross-clamp time of 127±26 min and a CPB time of 186±31 min. In Group 2, these values rose to 159±30 min and 232±49 min, respectively. The highest durations were observed in Group 3, with a mean cross-clamp time of 205±46 min and a mean CPB time of 278±48 min. These intergroup differences in operative times were statistically significant (p<.05) (Table 3).

Table 3. Perioperative outcomes

Five (7.0%) patients required permanent pacemaker (PPM) implantation. Two patients received pacemakers in the early postoperative period due to atrioventricular block, and three patients developed sinus node dysfunction necessitating pacing during long-term follow-up. Of these five patients, four underwent concomitant tricuspid valve surgery, while the remaining patient had combined aortic and MV surgery. Notably, none of the patients in Group 1 required PPM implantation during either the immediate postoperative phase or the follow-up period.

The mean follow-up was 26±2 months. At final follow-up, 88.7% of patients (63/71) were free from ATAs, as determined by 24-h Holter monitoring or pacemaker interrogation. Among them, three patients (18.8%) in Group 1, seven patients (16.3%) in Group 2, and four patients (33.3%) in Group 3 were still receiving antiarrhythmic drug therapy. Thus, 49 patients (69.0%) remained in sinus rhythm without the use of antiarrhythmic drugs. Groupspecific freedom from ATAs at different follow-up intervals is visualized in Figure 1. In Group 1, all patients (100%) maintained freedom from ATAs at six months (16/16), one year (15/15), two years (9/9), and three years (8/8). In Group 2, freedom from ATAs was 95.3% at six months (41/43), 91.2% at one year (31/34), 78.9% at two years (15/19), and 80.0% at three years (8/10). Group 3 patients demonstrated freedom from ATAs of 91.7% at six months (11/12), 91.7% at one year (11/12), 90.0% at two years (9/10), and 87.5% at three years (7/8). There were no statistically significant differences in freedom from ATAs between the groups at any time point (p>0.05) (Figure 2).

Figure 1. Post Cox-Maze IV rhythm results. (a) Overall cohort, (b) Group 1, (c) Group 2, (d) Group 3.
FFAF: Freedom from atrial fibrillation; AF: Atrial fibrillation.

Figure 2. Kaplan-Meier curves showing freedom from ATA following CM-IV surgery. (a) Overall cumulative ATA-free survival in the study cohort (n=71). (b) Cumulative ATA-free survival stratified by procedural complexity.
ATA: Atrial tachyarrhythmias; CM-IV: Cox-Maze IV; Group 1 (CM-IV + 1 concomitant procedure, n=16), Group 2 (CM-IV + 2 procedures, n=43), and Group 3 (CM-IV + ≥3 procedures, n=12). No statistically significant difference was observed among groups (log-rank p>0.05).

Six patients died during follow-up (8.5%). Causes included intracranial hemorrhage (n=1), infective endocarditis (n=2), chronic obstructive pulmonary disease (COPD) exacerbation (n=1), lung cancer (n=1), and non-cardiac sepsis (n=1). Only one thromboembolic event occurred (Group 2). None of the deaths were attributed directly to the CM-IV procedure.

Discussion

The present study presents one of the first detailed analyses of CM-IV outcomes in a population where AF was addressed not as a primary or secondary indication, but often as a tertiary or higher concomitant procedure. Despite the high procedural complexity, including a substantial proportion of patients requiring three or more additional operations, CM-IV yielded excellent rhythm outcomes, with 88.7% freedom from ATAs at a mean follow-up of 26 months. These results are consistent with established literature reporting freedom from AF rates of 75 to 90% at mid- to long-term follow-up following CM-IV.[6-8,16]

In our study, more than 70% of patients required two or more concomitant cardiac procedures in addition to CM-IV, a clinical reality that contrasts sharply with the majority of previous reports. Ad et al.[14] and McCarthy et al.[13] analyzed outcomes in cohorts where 70% or more of patients underwent CM-IV as an adjunct to a single primary operation such as MV repair or replacement. Similarly, in the work by Gerdisch et al.,[18] 58% of patients underwent only one concomitant procedure. These more controlled settings may not fully reflect the surgical realities in many developing nations, where rheumatic disease and late referral often necessitate multivalvular or multistructural procedure.

A valuable comparison can be drawn with the Chinese cohort published by Yu et al.,[19] which included a patient population remarkably similar to ours in terms of surgical complexity. In the aforementioned study, nearly 30% of patients underwent CM-IV alongside three or more additional cardiac procedures. Notably, this high level of procedural complexity was not associated with increased recurrence of atrial arrhythmias, reinforcing the idea that lesion completeness, rather than surgical burden, dictates rhythm success. Our findings strongly echo this conclusion and offer further support from a different geographic and clinical context.

Our findings align with the growing body of international data highlighting both the effectiveness and underutilization of surgical AF ablation. Studies from the United Kingdom,[12] China,[19] and Australia[20] demonstrate that despite robust guideline recommendations, real-world adoption of AF surgery remains as low as 7.7%. Mistirian et al.[12] reported that, even in high-volume centers, comprehensive lesion sets such as CM-IV are performed in only a minority of eligible patients.

More i mportantly, t he s urgical p rinciple underlying the CM-IV procedure is anatomical rather than disease-specific. The creation of transmural lines of conduction block, regardless of additional procedures performed, is the cornerstone of durable rhythm success. Cox[21] emphasized that the goal of the Maze procedure was to restore electrical isolation of critical atrial zones through anatomically grounded lesion sets, a principle that remains valid even in complex reoperative fields. While the CM-III procedure demonstrated excellent long-term rhythm outcomes through the "cut-and-sew" technique, its widespread adoption was limited by prolonged operative times and the increased bleeding risk associated with multiple atriotomies. In the original description of CM-III by the St. Louis group, although 198 patients underwent AF surgery, only 86 had any concomitant procedure, and just 15 patients received two concomitant interventions.[22] In contrast, the development of the CM-IV procedure, which utilizes energy sources rather than incisions to create lesion sets, has significantly enhanced the reproducibility and feasibility of surgical ablation, particularly in patients undergoing multiple concomitant cardiac surgeries.

In our study, operative complexity did not independently predict recurrence. Even in Group 3, with ≥3 procedures, freedom from ATAs at 36 months was 87.5%, comparable to simpler groups. These findings argue that surgical AF ablation should not be withheld in complex cases solely due to the number of concomitant procedures, provided that the full lesion set can be safely delivered.

In our cohort, the PPM implantation rate was 7.0%. While this may appear relatively high, it is of utmost importance to interpret this figure in light of the complexity of concomitant procedures and available literature. Prior studies have reported pacemaker rates ranging from 4.2 to 9.2% following surgical ablation, particularly in patients undergoing biatrial lesion sets or tricuspid valve surgery.[7,18,23] Among our five patients requiring pacing, only two received pacemakers for early postoperative atrioventricular block. The remaining three developed presyncope episodes during follow-up, and prolonged pauses were documented on extended Holter monitoring while in sinus rhythm. These cases were attributed to sinus node dysfunction, potentially unmasked by the absence of AF as an escape rhythm after successful ablation. Notably, four of these five patients had undergone concomitant tricuspid valve surgery, and the fifth had combined aortic and MV replacement. Given these coexisting procedural factors, the need for pacing in our series cannot be solely attributed to the CM-IV procedure. This aligns with previous reports suggesting that right atrial lesions and tricuspid interventions may increase the risk of postoperative conduction disturbances.[6,19] Thus, while our pacemaker rate is within reported ranges, it reflects the surgical complexity of the studied population rather than a procedure-specific complication.

Our findings are further supported by several national studies evaluating surgical ablation techniques under diverse clinical settings. In a mid-term outcome study by Arnaz et al.,[23] surgical cryoablation performed alongside other cardiac procedures achieved sinus rhythm in 90.9% of patients at discharge, with very low recurrence during follow-up, even in robotic-assisted cases, reinforcing the value of full lesion sets regardless of surgical access route. Similarly, Ezelsoy et al.[24] demonstrated that both monopolar and bipolar radiofrequency ablation added to mitral surgery provided comparable long-term sinus rhythm maintenance, highlighting that energy source may be less influential than lesion completeness in achieving durable outcomes. In our patient cohort, where complex procedures were frequent, this principle appears consistent, as the number of concomitant operations did not compromise CM-IV efficacy. The importance of transmural conduction block was also underscored in the study by Sarıcaoğlu et al.,[25] which reported a 90.6% sinus rhythm success at one year using biatrial ablation with intraoperative monitoring in patients undergoing valve surgery. Moreover, Özçınar et al.[26] emphasized the safety and effectiveness of cryoablation combined with mitral and tricuspid interventions in patients with significant left atrial enlargement, mirroring our subgroup that required three or more simultaneous procedures. These national data validate that, even in high-risk and anatomically complex cases, surgical ablation yields substantial rhythm success when performed with standardized, anatomically grounded lesion sets.

While our data support the feasibility and efficacy of CM-IV in high-complexity patients, the reluctance to perform AF surgery in such settings is likely multifactorial. Perceived technical difficulty, increased CPB time, and uncertainty regarding long-term benefit may deter surgeons. Yet, as our results and others have shown, these concerns may be unfounded. The present study reinforces the notion that surgical ablation is not only safe, but highly effective even in the context of multiple concurrent procedures, and its continued underutilization represents a missed opportunity for improving longterm outcomes.

The main limitations to this study include its single-center, retrospective design and lack of continuous rhythm monitoring in all patients. Additionally, data regarding freedom from AF off antiarrhythmic drugs were not uniformly available. Although AF burden would have provided deeper insights, this requires extended continuous monitoring, which is not routinely available or reimbursed in our setting. The relatively small sample size, particularly in Groups 1 and 3, limits the power of subgroup comparisons and may affect the generalizability of rhythm success across varying procedural complexities. Nonetheless, the consistency of outcomes across all groups and alignment with previously published literature strengthen the validity and relevance of our findings. Although several studies have identified predictors of ATA recurrence following surgical ablation, such as age, AF chronicity, left atrial size, and early postoperative arrhythmias, our study did not include a multivariable risk analysis due to the limited sample size and low number of rhythm failure events, which would preclude a statistically reliable model.

In conclusion, our study demonstrates that Cox-Maze IV is effective in restoring sinus rhythm in patients undergoing increasingly complex cardiac operations. The number of concomitant procedures did not adversely impact rhythm outcomes. These findings support broader application of surgical ablation for atrial fibrillation, even in patients undergoing three or more concurrent cardiac procedures.

Acknowledgements: The authors gratefully acknowledge the contributions of the surgical team, nursing staff, and administrative personnel at Koşuyolu High Specialization Training and Research Hospital for their support during data collection and follow-up. We also extend our gratitude to Simge Aylanç for her valuable assistance in data collection.

Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions: Study conception, design, supervision, critical revision, and drafting of the manuscript: T.A.; Data collection, statistical analysis, interpretation: F.Y.; Data acquisition, literature review, and manuscript preparation: F.B.; Surgical supervision, interpretation, and critical review: K.K.; Methodological guidance, surgical technique consultation, and final approval of the manuscript: R.J.D.

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding: The authors received no financial support for the research and/or authorship of this article.

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