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 procedure
37,38. 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 thereafter
3. 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 guidelines
39,44. 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.