Cox-Maze IV vs Cox-Maze IV and Mitral Valve Procedure for AF
Cox-Maze IV vs Cox-Maze IV and Mitral Valve Procedure for AF
In this study, perioperative outcomes and late efficacy were compared between patients having a stand-alone CMIV and those having concomitant mitral surgery. Previous studies from our institution and others usually have compared the stand-alone Cox-Maze procedure to a combined cohort of patients receiving a Cox-Maze procedure in addition to multiple concomitant procedures, including coronary artery bypass grafting, aortic valve replacement, and MV repair. Because the diseases prompting these concomitant operations are the result of multiple heterogenous pathologies, it is difficult to interpret the results from a single "concomitant" cohort. It was for this reason that this study was designed to compare outcomes in patients with lone AF to those with AF and concomitant mitral disease. This comparison is important for two reasons. First of all, AF ablation is performed much more commonly in the setting of concomitant mitral disease than for lone AF. In a recent study, five times as many surgical ablations were performed in the US in patients undergoing mitral surgery than for lone AF. Second, patients with MV disease often have enlarged LA from either chronic volume or pressure overload. This may result in different mechanisms of AF in this population, which could impair procedural success. Studies have shown that LA diameter is a risk factor for late recurrence of AF after a Cox-Maze procedure.
In our study, the efficacy of the CMIV for both stand-alone AF and when combined with a MV procedure was similar with respect to freedom from AF and antiarrhythmic agents at both one and two years. This is in agreement with our previous data showing comparable efficacy at one year using either the CMIII or the CMIV procedure, and shows that these good results were maintained at two years.
As expected, the two groups had different demographics. Patients who received stand-alone CMIV procedure tended to be predominantly male, younger and had a higher incidence of longer standing persistent AF. Moreover, half of the patients had failed a previous catheter ablation. The concomitant group on the other hand had more patients with NYHA class III or IV symptoms and significantly larger LAs. Despite these differences, the efficacy of the CMIV was similar in both groups, highlighting the efficacy of the CMIV procedure for the treatment of AF in both populations.
Not surprisingly, there was a significant difference in the perioperative morbidity, mortality and 30-day mortality between the groups. In a previous report from our institution, 30-day mortality was not significant. However, the total number of patients in this study was increased by 57% compared to our previous publication.
Major complication rates were also significantly increased in the concomitant group, primarily because of the need for reoperation for bleeding and an IABP. This is consistent with the fact that patients undergoing concomitant MV surgery were older, sicker and had longer cross clamp and CPB times. This increase in overall complication rate likely accounts for the one day increase in both ICU and hospital LOS.
The multivariate analysis of risk factors for recurrent ATA in this large cohort of over 350 patients was informative. In agreement with prior studies from our group, the failure to perform a box-lesion around the pulmonary veins and posterior left atrium was a predictor of recurrence. The increased risk of recurrence seen with a preoperative pacemaker is a new observation and is likely due to the improved power of this study in detecting smaller differences in outcomes. Since the majority of pacemakers were implanted for sick sinus syndrome, this finding suggests that patients with intrinsic sinus node dysfunction may have higher recurrence rates, possibly due to the known increased incidence of premature atrial contractions in these patients which can act as a trigger for recurrent AF.
The presence of early postoperative ATA as a predictor of late recurrence was in agreement with previous reports in the literature. This finding suggests that part of the substrate for early and late ATA may be similar. However this finding needs to be put into perspective. In patients undergoing concomitant MV and CMIV procedures, early ATA were present in 63% of patient but at two years only 10% of patients had recurrent ATA. Thus, it is important to remember that the majority of patients with early ATA remain free of ATA at two years.
Surprisingly, LA size was not a predictor in this multivariate analysis in contradiction to other studies which have shown this to be an important variable for failure. This may have been due to the introduction of the box-lesion set. In these patients, isolation of the entire posterior LA may effectively decrease LA size from an electrophysiological standpoint and reduce the substrate available for maintaining AF, thus negating the effect of an enlarged left atrium.
This study has several limitations. While the majority of our patients did have 24-hours of continuous cardiac monitoring after six months, there were still some who only had ECGs leading to a possible underestimation in the incidence of recurrent AF. In addition, this study was a retrospective review which introduces inherent selection biases, that could potentially be avoided if performed in a randomized fashion. However, all data were collected prospectively and this was a series of consecutive patients. While this series did show that efficacy was maintained at two years, it did not determine whether failures were due to an inability to properly complete the lesion set or because the underlying mechanism of AF in these patients was not able to be eliminated with a Cox-Maze procedure. It is our impression that failures occur because of advanced atrial remodeling and subsequent substrate modification such as atrial fibrosis. In this setting, reentry can be sustained in very small areas of atria, making it virtually impossible to eliminate AF with a Cox-Maze procedure. Finally, the AF burden was not quantitated in this study. Future studies using implantable loop recorders (ILRs) are worth considering to provide this information.
In conclusion, patients receiving a CMIV procedure have high rates of freedom from AF at one and two years regardless of the addition of a MV procedure. Perioperative complications were increased in patient undergoing concomitant MV surgery resulting in a longer hospital stay and higher 30-day mortality. Further advances in surgical techniques such as minimally invasive approaches may help to offset these differences.
Discussion
In this study, perioperative outcomes and late efficacy were compared between patients having a stand-alone CMIV and those having concomitant mitral surgery. Previous studies from our institution and others usually have compared the stand-alone Cox-Maze procedure to a combined cohort of patients receiving a Cox-Maze procedure in addition to multiple concomitant procedures, including coronary artery bypass grafting, aortic valve replacement, and MV repair. Because the diseases prompting these concomitant operations are the result of multiple heterogenous pathologies, it is difficult to interpret the results from a single "concomitant" cohort. It was for this reason that this study was designed to compare outcomes in patients with lone AF to those with AF and concomitant mitral disease. This comparison is important for two reasons. First of all, AF ablation is performed much more commonly in the setting of concomitant mitral disease than for lone AF. In a recent study, five times as many surgical ablations were performed in the US in patients undergoing mitral surgery than for lone AF. Second, patients with MV disease often have enlarged LA from either chronic volume or pressure overload. This may result in different mechanisms of AF in this population, which could impair procedural success. Studies have shown that LA diameter is a risk factor for late recurrence of AF after a Cox-Maze procedure.
In our study, the efficacy of the CMIV for both stand-alone AF and when combined with a MV procedure was similar with respect to freedom from AF and antiarrhythmic agents at both one and two years. This is in agreement with our previous data showing comparable efficacy at one year using either the CMIII or the CMIV procedure, and shows that these good results were maintained at two years.
As expected, the two groups had different demographics. Patients who received stand-alone CMIV procedure tended to be predominantly male, younger and had a higher incidence of longer standing persistent AF. Moreover, half of the patients had failed a previous catheter ablation. The concomitant group on the other hand had more patients with NYHA class III or IV symptoms and significantly larger LAs. Despite these differences, the efficacy of the CMIV was similar in both groups, highlighting the efficacy of the CMIV procedure for the treatment of AF in both populations.
Not surprisingly, there was a significant difference in the perioperative morbidity, mortality and 30-day mortality between the groups. In a previous report from our institution, 30-day mortality was not significant. However, the total number of patients in this study was increased by 57% compared to our previous publication.
Major complication rates were also significantly increased in the concomitant group, primarily because of the need for reoperation for bleeding and an IABP. This is consistent with the fact that patients undergoing concomitant MV surgery were older, sicker and had longer cross clamp and CPB times. This increase in overall complication rate likely accounts for the one day increase in both ICU and hospital LOS.
The multivariate analysis of risk factors for recurrent ATA in this large cohort of over 350 patients was informative. In agreement with prior studies from our group, the failure to perform a box-lesion around the pulmonary veins and posterior left atrium was a predictor of recurrence. The increased risk of recurrence seen with a preoperative pacemaker is a new observation and is likely due to the improved power of this study in detecting smaller differences in outcomes. Since the majority of pacemakers were implanted for sick sinus syndrome, this finding suggests that patients with intrinsic sinus node dysfunction may have higher recurrence rates, possibly due to the known increased incidence of premature atrial contractions in these patients which can act as a trigger for recurrent AF.
The presence of early postoperative ATA as a predictor of late recurrence was in agreement with previous reports in the literature. This finding suggests that part of the substrate for early and late ATA may be similar. However this finding needs to be put into perspective. In patients undergoing concomitant MV and CMIV procedures, early ATA were present in 63% of patient but at two years only 10% of patients had recurrent ATA. Thus, it is important to remember that the majority of patients with early ATA remain free of ATA at two years.
Surprisingly, LA size was not a predictor in this multivariate analysis in contradiction to other studies which have shown this to be an important variable for failure. This may have been due to the introduction of the box-lesion set. In these patients, isolation of the entire posterior LA may effectively decrease LA size from an electrophysiological standpoint and reduce the substrate available for maintaining AF, thus negating the effect of an enlarged left atrium.
This study has several limitations. While the majority of our patients did have 24-hours of continuous cardiac monitoring after six months, there were still some who only had ECGs leading to a possible underestimation in the incidence of recurrent AF. In addition, this study was a retrospective review which introduces inherent selection biases, that could potentially be avoided if performed in a randomized fashion. However, all data were collected prospectively and this was a series of consecutive patients. While this series did show that efficacy was maintained at two years, it did not determine whether failures were due to an inability to properly complete the lesion set or because the underlying mechanism of AF in these patients was not able to be eliminated with a Cox-Maze procedure. It is our impression that failures occur because of advanced atrial remodeling and subsequent substrate modification such as atrial fibrosis. In this setting, reentry can be sustained in very small areas of atria, making it virtually impossible to eliminate AF with a Cox-Maze procedure. Finally, the AF burden was not quantitated in this study. Future studies using implantable loop recorders (ILRs) are worth considering to provide this information.
In conclusion, patients receiving a CMIV procedure have high rates of freedom from AF at one and two years regardless of the addition of a MV procedure. Perioperative complications were increased in patient undergoing concomitant MV surgery resulting in a longer hospital stay and higher 30-day mortality. Further advances in surgical techniques such as minimally invasive approaches may help to offset these differences.