4. Discussion
The outcomes of concomitant Cox-Maze and PVI during MV surgery have been extensively evaluated, but comparative data on the mortality and freedom from AF are still limited. In this systematic review, we investigated comparison of mid-term clinical outcomes between these two surgical ablation techniques. Across most studies with included AF patients undergoing MV surgery, concomitant Cox-Maze procedure was associated with a higher freedom from AF at 12-month follow-up when compared with concomitant PVI. Secondly, our systematic review suggested that RCTs have demonstrated similar 12-month mortality between concomitant Cox-Maze and PVI, while observational studies have shown survival benefit of Cox-Maze at 12-month follow-up.
Importantly, several long-term studies demonstrated a survival benefit of AF ablation surgery 27. Even more, risk-adjusted analysis confirmed the safety of concomitant ablation surgery and found that the additional procedure is not associated with increased Society of Thoracic Surgeons morbidity or mortality 1,28. Interestingly, Mehaffey and colleagues reported recently that surgeons perform concomitant Cox-Maze IV surgery among 27-78% of patients depending on whether they reported barriers to implementation of evidence-based recommendation 29. However, a clinical practice guideline recommended that surgical ablation for symptomatic AF in the setting of left atrial enlargement (>4.5 cm) and more than moderate mitral regurgitation by PVI alone is not recommended (Class III no benefit, Level C expert opinion) 3.
Although the association of concomitant Cox-Maze and freedom from AF is evident, our results indicated that more RCTs with longer standardized follow-up (at least 2-year) are required in order to clarify the benefits of concomitant Cox-Maze in AF patients undergoing MV surgery. In addition, institutional experience is of paramount importance due to the fact that a center might have a higher morbidity or early postoperative mortality while introducing the Cox-Maze technique. Therefore, clear advantage of this technique remains valid for centers with substantial experience in antiarrhythmic surgery. Furthermore, the reviewed data strongly suggest that both XCT and CPB time did not seem to be prolonged with concomitant Cox-Maze procedure22,24,25, although they were not consistently reported across all the studies.
The benefit of concomitant Cox-Maze in mitral patients with AF is in line with the results of other studies that have not only shown both freedom from AF and mortality benefit, but have also demonstrated improvement in quality of life 30-33. However, our subgroup analysis with meta-analysis of RCTs did not suggest that there is a significant survival benefit of concomitant Cox-Maze procedure among RCTs. This can be explained by the fact that one of the RCTs was potentially underpowered and biased as many cases were excluded from randomization over the study period 22. Furthermore, in the same RCT all patients with postoperative AF were intensely treated in order to restore the sinus rhythm. However, it has also been difficult to demonstrate a survival benefit in mitral patients after concomitant Cox-Maze procedure in other reports 34. This may be related to a few reasons such as limited cohorts and short follow-up study periods in RCTs. On the other hand, several observational studies with larger data sets have reported significant survival benefits 24,25. However, given that AF has been clearly demonstrated to be an independent predictor of mortality, restoration of sinus rhythm is vital for quality of life and survival.35
Previous studies have also reported that the Cox-Maze procedure in AF patients undergoing concomitant cardiac surgery has a potential protective effect from stroke and thromboembolism in the long-term period.36 Unfortunately, these clinical outcomes along with other potential outcomes of interest (re-hospitalization, permanent pacemaker implantation) were poorly reported in both RCTs and observational studies included in this systematic review. The available data from the studies included in our systematic review has demonstrated that early postoperative morbidity related to the risk of stroke was not increased with the performance of concomitant Cox-Maze procedure.24,26  More importantly would be to see the evidence in future trials whether restoration of sinus rhythm in these patients with concomitant Cox-Maze procedure can improve long-term survival and quality of life while reducing the risk of late stroke. However, despite this reported efficacy of Cox-Maze, the widespread acceptance has been limited due to the technical complexity of the procedure and its possible complications such as the need for permanent pacemaker.
Interestingly, we found concomitant Cox-Maze to be associated with somewhat lower rates of MV repair. This can be partially explained by the technical complexity of this procedure and, therefore, greater likelihood of decision to proceed with valve replacement instead of repair when considering performing more complex ablation procedure. However, for optimal outcomes the surgeons should become more skilled in the Cox-Maze technique through fellowship training, peer-to-peer education, or proctorship 3.
There are certain limitations to this systematic review. Although all the available literature has been examined, the quality of the studies included must be considered. Several eligible studies were retrospective cohort studies and only 3 RCTs comparing both concomitant ablation procedures were found. Most studies did not report the outcomes of long-term mortality (>12 months), postoperative stroke or re-hospitalization rate due to AF as well as other relevant clinical outcomes. However, sufficient studies were available to evaluate mid-term outcomes between both subgroups and standardized Cox-Maze lesion set patterns were used in all the studies. On the other hand, the available data was insufficient to allow a robust meta-analysis as a primary goal of our study. It is also well established that there is no difference in outcomes between the cut-and-sew and a cryoablation/bipolar technique of Cox-Maze procedure37,38. In addition, some studies did not perform standardized follow-up screening for outcome assessment, nor did they report antiarrhythmic and anticoagulation protocols, as recommended by current professional organizations 39-41. In our opinion, each patient should receive a standardized postoperative treatment with amiodarone, if not contraindicated, for at least 6 weeks of duration 42,43. The number of patients lost to follow-up was not reported in all the studies, therefore the reported outcomes might not reflect the true outcomes within the studies. Future trials can be improved by adhering to this performance and reporting standards to better evaluate the effect of concomitant AF surgery. Therefore, we would like to emphasize that the standardized postoperative follow-up protocol should include regular outpatient visits during the first 24 months and annually thereafter3. A 12-lead electrocardiogram should be obtained at every follow-up visit while a 24-hour Holter monitor at every follow-up visit after 6 months, consistent with established guidelines39,44. Still, even with the follow-up Holter monitoring, not all events may be captured. Long-term outcome assessment may help evaluate whether type of concomitant AF surgery influences mortality, neurological or thromboembolic risk, which are the primary goals of AF treatment. Large high-quality randomized trials evaluating the effect of different AF surgery types and lesion sets and comparing outcomes within different AF subgroups could provide guidance about which intervention has the most favorable efficacy and safety profile.