Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery:
Are There Gender Differences in Outcomes After the Cox-Maze Procedure for Atrial Fibrillation?
Henry, Linda PhD; Hunt, Sharon MBA; Holmes, Sari D. PhD; Martin, Lisa M. PhD; Ad, Niv MD
From the Inova Heart and Vascular Institute, Falls Church, VA USA.
Accepted for publication March 30, 2013.
Disclosure: Niv Ad, MD, is a consultant for Medtronic, Inc., Minneapolis, MN USA, Atricure, Inc., Cincinnati, OH USA, and Estech, Inc., San Ramon, CA USA. Linda Henry, PhD, Sharon Hunt, MBA, Sari D Holmes, PhD, and Lisa Martin, PhD, declare no conflict of interest.
Address correspondence and reprint requests to Linda Henry, PhD, Cardiac Surgery Research, Inova Heart and Vascular Institute, Falls Church, VA 22042 USA. E-mail: email@example.com.
Atrial fibrillation (AF) management suggests that women do not tolerate medication rhythm control strategies as well as men do; however, AF percutaneous catheter ablation has been found to be favorable. The study purpose was to compare the sex-based outcomes for patients who undergo the Cox-Maze procedure for AF.
Data were collected through our AF surgical ablation registry. Rhythm was verified by electrocardiogram and 24-hour holter at 6 and 12 months. General health-related quality of life (Short-Form 12) and specific AF symptom burden (Atrial Fibrillation Symptom Checklist: Frequency and Severity, version 3) were obtained at baseline and 12 months.
Since 2005, a total of 540 patients have undergone a Cox-Maze procedure (34% were women). The women presented with higher operative risk [additive European System for Cardiac Operative Risk Evaluation (EuroSCORE), 6.71 ± 2.61 vs 5.25 ± 2.80, t = 5.85, P < 0.001], higher rates of congestive heart failure (49% vs 32%, P < 0.001), and more concomitant mitral valve procedures (32% vs 19%, P = 0.001). Perioperative outcomes were similar. Return to sinus rhythm off antiarrhythmics were not different at 6 and 12 months (78% vs 75%, P = 0.53, and 81% vs 80%, P = 1.00, respectively). Cumulative 2-year survival (93.9% for the men and 89.3% for the women) was not different for all-cause mortality (hazard ratio, 1.47; confidence interval, 0.68–3.21; P = 0.33) and cardiac-related mortality [women: 10/14 (71%) vs men 7/11 (64%), P = 1.00]. Health-related quality of life showed significant improvement; AF symptoms significantly decreased across the sexes.
Outcomes after the Cox-Maze procedure are similar across sex. Atrial fibrillation surgical ablation should be considered a treatment option for women—it is safe and effective, improves general health-related quality of life, and reduces AF symptom burden.
Atrial fibrillation (AF) is the most common arrhythmia in the adult population, of which recently published data suggest that more than 2.3 million people in the United States are affected by AF. On the basis of the same data source, it is expected that by 2050, a total of 5.6 million people in the United States will have AF.1 The occurrence of AF is associated with age, race, and sex, such that the prevalence of AF in those younger than 55 years is 0.1%; but for those older than 80 years, 9%. Whites older than 50 years are affected at a higher rate compared with African Americans, and men have double the prevalence rate than do women.1,2
The latest publications estimate that the rate of AF occurrence in women is approximately one in four during one’s lifetime.3 From the recent Atherosclerosis Risk in Communities study, investigators determined that the crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1000 person-years in white men, white women, African American men, and African American women, respectively. They determined that the cumulative risk for AF by the age of 80 years was 21%, 17%, and 11% in white men, white women, and both African American men and women, respectively.4 The lower rate discrepancy in the African American population could be due to the lack of earlier appropriate monitoring.5 Some would also argue that the incidence of AF should be considered the same for both men and women because there are more women older than 75 years than men, making the overall absolute number of men and women with AF the same.6
Evidence related to the management of AF suggests that women do not tolerate antiarrhythmic medication rhythm control strategies as well as men do. Results from the Atrial Fibrillation Follow-up Investigation of Rhythm Management and the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation studies indicated that women did not fare as well as men did with rhythm control strategies (antiarrhythmic drugs and electrical cardioversion).7–9 Women experienced more adverse events including increased thromboembolisms and stroke, heart failure, adverse effects related to antiarrhythmic medications, increased recurrences of AF after cardioversion, and difficulty maintaining therapeutic international normalized ratios. Thus, there has been a call for more rate control strategies instead of rhythm control strategies to be used for women, especially in women with heart failure.7–9
On the contrary, results from several studies investigating sex-based outcomes after percutaneous catheter ablation for AF that have been published recently were favorable.10–12 Their findings were that women do very well after the percutaneous catheter ablation procedure although they may experience more postprocedural bleeding. However, there has been no study published on the outcomes of women after a surgical ablation procedure for AF. The purpose of this study was to examine the short- and long-term outcomes of female patients when compared with male patients after undergoing the Cox-Maze procedure for AF.
We prospectively collected study data related to the patients’ surgical and postoperative course. All patients underwent the full Cox-Maze III/IV procedure, which includes the left atrial appendage disarticulation by multiple surgeons.13–15 The lesion pattern used cryothermia only in most patients (56%), and a combination of bipolar radiofrequency and cryothermia was used in 42% to complete the full lesion set.13–15
All patients were followed longitudinally through office visits and mailed surveys at 3, 6, 12, 18, and 24 months and then yearly thereafter. The data obtained from all patients were captured using our self-developed AF follow-up registry. The registry was developed in a way that all patients who present for surgical ablation of AF procedures are captured at the time of their surgery and a longitudinal record is started. By capturing patients prospectively at the time of their surgery, all follow-up mailed survey information is generated automatically and mailed to the patient at prescribed time points until the patient dies or asks to be withdrawn.16,17 These data were then merged through a statistical platform with data collected and stored in our local Cardiac Surgery Research database. Our response rate to the follow-up program is 80% over time. The most frequent reasons for missing information for either group were not different and included the following: the patients were operated on before our follow-up system was in place, the patients did not have a medical appointment, or the physician offices refused to send the patient information. This study was reviewed and approved by our institutional review board (institutional review board numbers 6.037, 7.054, and 6.022).
Our patients’ sense of their well being is captured through a general health-related quality of life (HRQL) platform [Short-Form 12 (SF-12)] and AF disease–specific tool (Atrial Fibrillation Symptom Checklist: Frequency and Severity, version 3). All patients were asked to complete a baseline (preoperative) HRQL survey and were mailed a follow-up survey at 6, 12, 18, and 24 months after surgery. We used the SF-12, which has long been considered a reliable and validated instrument for use across many disease populations and is easy to administer, being particularly adept for use in self-report situations.18 The family of SF instruments has been used and validated in the cardiac surgery population. The instrument measures eight domains of HRQL and two summary scores: physical composite and mental composite. Scores range from 0 to 100 and are standardized18 to a mean of 50 and an SD of 10. A higher score refers to better HRQL and can be compared against age group norms. Atrial fibrillation–related frequency and severity of the patients’ symptoms were assessed using the Atrial Fibrillation Symptom Checklist: Frequency and Severity (version 3), a well-validated tool that has been used in several studies to include the recent Atrial Fibrillation Follow-up Investigation of Rhythm Management trial.19–21 This survey consists of 16 symptom items. The maximum frequency score is 64, and the maximum severity score is 48. Higher scores indicate more symptoms and a higher degree of severity when experiencing the symptom.19 In a validation study, subjects without AF reported mean frequency and severity scores of 10 and 8 points, respectively, whereas patients with AF reported scores more than twice that of the subjects without AF.22 Implementation of this survey began partway through our follow-up program. Therefore, the sample size for these data is smaller than for other elements of this study. Data were available for baseline and 6-month follow-up in 42 female patients and 74 male patients.
The Society of Thoracic Surgeons definitions were used to report major morbidities after surgery, which included in-hospital mortality (<30 days), stroke, prolonged ventilation (>24 hours), pneumonia, deep sternal wound infection, tamponade, renal failure with dialysis, reoperation for bleeding, and readmission within 30 days.23
Rhythm status for the patients was verified by 24-hour holter monitor and/or pacemaker interrogations. The Heart Rhythm Society definition of success (all documented atrial arrhythmias of >30 seconds are considered a failure) was used to determine the return to sinus rhythm rate at 6 and 12 months.24 All other clinical information during follow-up was collected prospectively at regular intervals (3, 6, 9, 12, 18, and 24 months and then yearly thereafter) via patient report and record review. The Social Security Index and the National Death Index were searched for follow-up deaths. In addition, we also offered a week-long monitoring at 6 months for the patients who reported being off their antiarrhythmic medications and were considered to be in a stable sinus rhythm by electrocardiogram or 24-hour holter, which is part of our regular follow-up monitoring.25,26 The patients’ compliance for the 1-week monitoring was 67% at 6 months. The patients declined for a variety of reasons, mainly insurance costs; did not want to participate because they felt great; or asked to be withdrawn from our study. For the patients who had a pacemaker, we requested a pacemaker interrogation at the 6-month period as an equivalent data to long-term monitoring.
The women and the men were compared using the χ2 test or two-sided Fisher exact test for categorical variables and Student’s t test for independent samples or the Mann-Whitney U test for continuous variables. The women and men were also compared on all clinical outcome measures using multivariate analyses (logistic or linear regression, as appropriate) to adjust for the following clinical covariates: age, left atrial size, duration of AF (months), coronary artery bypass graft surgery, valve surgery, minimally invasive versus midsternotomy incision, congestive heart failure, and additive European System for Cardiac Operative Risk Evaluation (EuroSCORE). Type of AF was not included in the covariate set because of multicollinearity and overlap with duration of AF. The set of clinical covariates was determined a priori on the basis of clinical and theoretical evidence regarding factors that may impact outcomes or may differ by sex. Cox proportional hazards regression analysis was conducted to evaluate the effect of sex on survival after adjustment for the clinical covariates. Mixed-model repeated-measures analysis of variance was used to evaluate changes in HRQL and AF symptom scores by sex. In addition, Student’s independent-samples t tests were used to compare each sex to their age and sex HRQL norms. For all analyses, a two-tailed P < 0.05 was used to determine significance. Statistical analysis was completed in the SAS/STAT software, version 9.1.3 of the SAS System for Windows (Cary, NC USA), or the Statistical Package for the Social Sciences version 17.0 (SPSS Inc. Chicago, IL USA).
Since 2005, a total of 638 patients have undergone surgical ablation for AF either as a stand-alone procedure or concomitantly with another procedure. Five hundred forty patients (34% were women) have undergone the full Cox-Maze III/IV procedure across multiple surgeons.13,14Table 1 compares the demographic and clinical characteristics. The women presented with a significantly higher additive EuroSCORE (6.71 ± 2.61 vs 5.25 ± 2.80, t = 5.85, P < 0.001) and logistic EuroSCORE (8.8% ± 9.4 vs 6.4% ± 7.5, P = 0.001), with more women having a history of congestive heart failure (49% vs 32%, χ2 = 14.5, P < 0.001), undergoing more concomitant surgeries for mitral valve disease (32% vs 19%, χ2 = 10.7, P = 0.001), requiring fewer coronary artery bypass surgeries (6% vs 12%, χ2 = 6.1, P = 0.01), and underwent fewer minimally invasive surgeries (8% vs 33%, P < 0.001). Previous failed left atrial catheter ablations (12% vs 20%, P = 0.03) and the number of electrical cardioversions (25% vs 42%, P < 0.001) were lower for the women. Despite the women carrying a higher operative risk, perioperative results demonstrated no differences between the sexes in major morbidities after surgery (stroke: 0.6% vs 0.3%, P = 1.00; operative death: 3.1% vs 2.0%, P = 0.52; prolonged ventilation of >24 hours: 8.1% vs 8.5%, P = 1.00; renal failure with dialysis: 2.5% vs 3.6%, P = 0.60; and readmissions within 30 days: 12% vs 13%, P = 0.77), but the women had a significantly longer median (interquartile range) length of stay in days [8 (5–11) vs 6 (4–8), Z = −5.8, P < 0.001; Table 2].
Multivariate analyses comparing the women and the men on all perioperative and postoperative clinical outcomes also found no significant effect of sex after adjustment for the clinical covariates, as described in the statistical methods. Furthermore, there was no significant difference between the women and the men for 2-year cumulative survival after adjustment for clinical covariates (hazard ratio, 1.47; confidence interval, 0.68–3.21; P = 0.33; Fig. 1). The total number of deaths at any time during the study (before and after discharge) was n = 55 and not different between the sexes (P = 0.17). For the patients with a known cause of death identified through the National Death Index (International Statistical Classification of Diseases, 10th Revision, codes were used for cause of death), there was also no significant difference in the number of women and men who died as a result of cardiovascular disease [women: 10/14 (71%) vs men 7/11 (64%), P = 1.00].
The return to sinus rhythm at 6 months and 12 months for the women was 93% and 94%, which was not significantly different than the men’s rate of return to sinus rhythm of 91% and 92%, respectively. The return to sinus rhythm was also similar for both women and men off antiarrhythmic medications at 6 months (75% vs 78%, P = 0.53). This relationship held steady at 12 months, when similar results were found (81% vs 80%, P = 1.00; Table 3). In the subset of patients who agreed and underwent 1-week monitoring at 6 months off antiarrhythmic medications (n = 169; 33% were women), we found the same trend for return to sinus rhythm for both groups (89% vs 93%, P = 0.55; Table 3). For the patients with pacemaker interrogation reports at 6 months (n = 27), return to sinus rhythm was also not different between the women and the men (92% vs 86%, P = 1.00).
Less than 20% of the patients in each group required electrical cardioversion at any time point during follow-up for return to sinus rhythm after the Cox-Maze III/IV procedure (χ2 = 0.01, P = 0.91). Less than 6% of the patients in each sex (P = 0.84) required a follow-up catheter ablation to restore sinus rhythm, with the most common reason being for atrial flutter (n = 21) in both groups [women: n = 7 (4 for atypical flutter, 2 for typical flutter, 1 unknown); men: n = 14 (5 for atypical flutter, 8 for typical flutter, and 1 unknown); Table 4]. Most patients in both sexes maintained their sinus rhythm after catheter ablation at their last known follow-up (women: 75% and men: 79%). Pacemakers were required after the Cox-Maze III/IV procedure in 3% of the women and 5% of the men (P = 0.39), with the most common reasons being for sick sinus syndrome and sinus node dysfunction.
In a mean ± SD follow-up period of 40.3 ± 24.4 months and 40.4 ± 24.6 months for the women and the men, respectively (t = 0.04, P = 0.97), we found no significant differences in postdischarge stroke/transient ischemic attack morbidity or the need for follow-up interventions to restore sinus rhythm (Table 4). In the female group, there was one patient who had an embolic stroke after discharge versus three patients in the male group (P = 1.00), which translates to a very low rate of 16.5 strokes per 10,000 person-years in women and 24.8 strokes per 10,000 person-years in men. Major bleeding events (defined as a bleed that required blood transfusion, hospitalization, or surgical intervention to control bleeding or intracranial hemorrhage after the 3-month blanking period) occurred in 3.3% of the women (9 total events) and 3.6% of the men (21 total events) during the follow-up period (P = 1.00). For the patients with at least one major bleeding event, the mean preoperative CHADS2 score did not differ between the women and the men (2.0 ± 0.9 vs 2.1 ± 1.0, P = 0.88). At the time of their first major bleeding event, 63% were on warfarin, and of those on warfarin, 50% were taking it for another appropriate clinical indication. Although the sample size is very small, the male patients were more likely to be on warfarin at the time of their first major bleeding event than were the women (85% vs 17%, P = 0.01).
Health-Related Quality of Life and AF Burden
In Figure 2, a comparison of the men and the women on all domains of the SF-12 at baseline and 6 months after surgery can be found. It is clear that the scores reported by the female patients were lower at all time points. The female patients scored significantly lower on baseline physical composite scores (P = 0.005) and mental composite scores (P = 0.04), physical composite scores at 6 months (P = 0.01), and many other domain scores shown in Table 4 at the baseline and 6-month time points. Although the women consistently reported lower HRQL scores than did their male counterparts, the women did show a significant improvement within their group from baseline to 12 months in physical HRQL (39.2 ± 10.9 to 46.7 ± 9.9, t = 5.3, P < 0.001) and mental HRQL (48.8 ± 12.0 to 52.5 ± 9.4, t = 2.5, P = 0.01).
Physical composite score of HRQL showed a significant effect of time (F = 48.6, P < 0.001) and sex (F = 5.2, P = 0.02). Figure 3 demonstrates the significant quadratic effect of time (F = 20.9, P < 0.001), such that all patients improved significantly between baseline and 6 months, but this improvement leveled out between 6 and 12 months after surgery (women: n = 71, men: n = 148). In addition, the main effect of sex can be seen in Figure 3, with higher physical composite scores in the male patients regardless of time point. However, the improvement trajectories for both sexes did not differ because there was no significant interaction of time and sex on physical composite scores (F = 1.1, P = 0.31). Both groups were lower on preoperative physical composite scores when compared with their age and sex norms (women: 39.2 vs 43.6, t = 3.6, P < 0.001; men: 43.3 vs 47.6, t = 4.2, P < 0.001). By 12 months, the women surpassed their age group and sex norms (47.2 ± 10.0, t = 3.0, P = 0.003) and the men were similar to their age and sex norms (49.2 ± 9.5, t = 1.7, P = 0.09). Also of note, when comparing the physical composite score of the patients who underwent stand-alone Cox-Maze surgery with those who underwent concomitant procedures (regardless of sex), both surgery groups improved similarly from baseline to 12 months after surgery (F = 0.27, P = 0.69), but the stand-alone group had higher physical composite scores regardless of time point (F = 10.8, P = 0.001). Therefore, improvement in HRQL after the Cox-Maze was not solely related to correction of other cardiac disease processes (coronary artery disease and/or valvular disease.
For general health scores of HRQL, there was a significant effect of time (F = 19.3, P < 0.001), but not for sex (F = 3.0, P = 0.08). Overall, general health scores improved from before surgery to 12 months after surgery; however, the significant interaction of time by sex (F = 3.7, P = 0.03) indicated that the improvement trajectories for general health differed by sex (women: n = 75, men: n = 157). As illustrated in Figure 4, the male patients had a linear improvement in general health scores from baseline through 12 months. In contrast, the female patients had a sharper improvement in general health scores from baseline to 6 months but a plateau in scores between 6 and 12 months after surgery. Therefore, the interaction of time by sex was quadratic in nature (F = 5.2, P = 0.02). By 12 months, both female and male patients surpassed their age and sex norms (women: t = 2.4, P = 0.02, and men: t = 2.7, P = 0.008).
Although there was a significant effect of time (F = 11.3, P < 0.001) on mental composite scores of HRQL (women: n = 71, men: n = 148), the women and the men increased similarly (F = 1.2, P = 0.31). At 12 months, the women were similar to their age and sex norms (t = 1.6, P = 0.10) but the male patients had surpassed their age and sex norms (t = 2.9, P = 0.004).
Patient-reported AF symptom frequency showed a significant effect of time (F = 81.3, P < 0.001), such that symptom frequency declined significantly between baseline and 6 months after surgery. There was also a significant main effect of sex, which indicated that the female patients reported greater overall symptom frequency regardless of time point (F = 9.1, P = 0.003). However, the men and the women showed similar improvement in overall AF symptom frequency (F = 0.2, P = 0.62). By 6 months, the women demonstrated a 40% decrease (P < 0.001) in their symptom frequency and a 37% decrease (P < 0.001) in their severity of symptoms, and the men, at 6 months, demonstrated a 54% decrease (P < 0.001) in symptom frequency and a 52% decrease in their reported severity of symptoms (P < 0.001).
Similarly to the AF frequency findings, patient-reported AF symptom severity showed a significant effect of time (F = 66.3, P < 0.001), such that symptom severity also declined significantly between baseline and 6 months after surgery. The main effect of sex was also found for symptom severity, which indicated that the female patients reported greater symptom severity regardless of time point (F = 9.8, P = 0.002). However, again, the men and the women showed similar improvement in AF symptom severity (F = 0.3, P = 0.58). In summary, the female patients did report significantly greater frequency and severity of AF symptoms at baseline (P = 0.048 and P = 0.04) and 6 months (P = 0.003 and P = 0.003), but the level of improvement in these symptoms after surgery was similar to that of the male patients.
Investigation into the more common AF symptoms showed that although the women and the men reported shortness of breath similarly before surgery (81% vs 84%, P = 0.80), by 6 months after surgery, more women were still reporting shortness of breath (64% vs 42%, P = 0.03). The same pattern of result was found for heart fluttering (52% vs 30%, P = 0.02) and heart racing (38% vs 18%, P = 0.02) at 6 months. Although the women had more complaints of shortness of breath, heart fluttering, and heart racing, they demonstrated within their group a significant decrease in their reporting of tiredness (↓36%, P < 0.001), heart fluttering (↓65%; P < 0.001), and heart racing (↓64%, P < 0.001) as well as a significant decrease in the severity of feeling tired (↓28%; P < 0.001) and heart fluttering (↓31%; P < 0.001). The men also showed a significant decrease in the reporting of tiredness (↓40%; P < 0.001), heart fluttering (↓73%; P < 0.001), and heart racing (↓78%, P < 0.001) as well as a significant decrease in the severity of their symptoms of tiredness (↓25%; P < 0.001) and heart fluttering (↓25%; P < 0.001).
When adjustment for AF symptom frequency improvement from baseline to 6 months was included in the model, improvement in physical composite score HRQL during the same time frame became nonsignificant (F = 1.04, P = 0.31), although the significant main effect for sex remained (F = 6.0, P = 0.02). This finding indicates that AF symptom reduction as a result of the Cox-Maze procedure accounts for a large portion of the significant improvement in physical HRQL that was found across both sexes.
This large cohort study assessed the short- and long-term outcomes of the female patients when compared with the male patients after the Cox-Maze procedure for AF. Outcome across sex seems equal both early and late postoperatively. These outcomes held true even when longer term monitoring (monitoring for 7 days and/or pacemaker interrogation) was used to verify their reported rhythm.
The operative risk for the female patients was slightly higher compared with that for the male patients as defined by the EuroSCORE. The female patients were noted to have higher rates of history of congestive heart failure, which is a consistent finding for women and AF.27 In addition, we found that the women needed more valve surgeries but fewer surgeries for coronary artery disease did their male counterparts. The fact that the women present sicker for an intervention is consistent with a study recently completed and published discussing sex bias and cardiovascular disease. Current findings note that the death rate from cardiovascular disease for women has exceeded the rate for men since 1984. Women now account for 52.1% of all cardiovascular-related deaths.28
Current reports also indicate that women with AF are at a higher risk for embolic stroke, are sicker, and are more symptomatic when experiencing AF.29–33 Each year, 55,000 more women than men have a stroke. According to a national report, in 2007, a total of 60.2% of total stroke deaths occurred in women.28 Evidence has also shown that the rate of embolic stroke occurs almost six times as frequently in patients with AF compared with those without AF, and these strokes are found to be more devastating and lethal especially among elderly women.27,32–35 In this current study, only one woman had a late embolic stroke after the Cox-Maze procedure. The stroke occurred at 12 months after surgery while in sinus rhythm, with a CHADS2 of 0. These results were not significantly different from the male group, which is an encouraging result. Despite women being sicker and having a higher risk for complications, the Cox-Maze procedure was found to be equally safe and effective for women and seems to significantly reduce the risk for stroke through the return of sinus rhythm and the disarticulation of the left atrial appendage.36,37
Recent findings for the treatment and outcomes of coronary artery disease have demonstrated that sex bias is present. Women tend to undergo fewer cardiac catheterizations and revascularization procedures than do men and have a higher in-hospital mortality than do men when admitted for acute coronary syndrome.38,39 These findings are also present for women who present to their cardiologist in AF, by whom they are treated less aggressively than their male counterparts are.39–44 Another reason for the delay of treatment may be that women present for nonpharmacological intervention later in their disease course when their presenting symptoms may have been misinterpreted and appropriate treatment is then not undertaken, making them at higher risk with increased rates of heart failure rates.38,45–48 This supposition has also been recently supported in an article published in the Journal of the American Medical Association, in which the authors found that female patients who presented with a non–chest pain myocardial infarction had significantly higher mortality than men did and were not receiving timely pharmacological and nonpharmacological interventions, to include being discharged home from the emergency department without any treatment.49
The predictors for the development of AF differ between men and women, which could also lead to the underdiagnosis of AF in women. Conen and colleagues50,51 found that blood pressure was strongly associated with the incidence of AF, with systolic blood pressure a better predictor than diastolic in women. Biomarkers such as C-reactive protein have also been associated with the development of AF in women without cardiovascular disease. This was a consistent finding in our cohort of female patients as well, in that they had undergone fewer cardioversions and ablations than their male counterparts had.
However, our findings are also similar to recent research results that indicate that sex bias is not evident among women who do receive an intervention for their cardiac disease process. Aguado-Romeo et al52 discerned that sex was not associated with higher in-hospital mortality in patients who undergo some kind of percutaneous cardiovascular procedure for coronary syndrome. However, their results were dependent upon patients being correctly diagnosed and treated; otherwise, mortality was higher in women than in men. Michelena et al10 and Santangeli et al11 found that catheter ablation for AF was successful and beneficial for the correctly selected patients of either sex, although women may encounter more procedural bleeding complications. They also found that women tended to be referred less often and later for catheter ablation than men did. Outcomes reported from the German Ablation Registry found that women experienced the same outcomes as men at 1 year after undergoing left atrial ablation for AF.12
Our results also indicate that women may be referred later in their disease course for treatment of their AF, but once they are sent for further interventional treatment and are operated upon for AF, their outcomes are very good. Women can expect to have the same return to sinus rhythm off antiarrhythmic medications at the respective follow-up time points and to encounter no significant difference in postoperative morbidities than men. Although the women’s follow-up HRQL scores and reporting of and severity of symptoms are significantly different from the men’s scores, the women’s scores within their group improved significantly. By 6 months, the women had a significant increase in the physical composite of their HRQL scores and experienced a significant decrease in their reported AF frequency and severity of their symptoms especially for tiredness and heart fluttering.
Another interesting finding of our study was that there was no statistical difference in cumulative 2-year survival between the women and men. This result is encouraging in that Miyasaka et al53 found that the development of AF conveyed a high risk for new coronary events in women. Therefore, the finding that survival is high in both groups and not significantly different is encouraging for women to seek curative treatment of their AF.
The results demonstrated in this study could be a result of the performance of the full Cox-Maze procedure. Confusion abounds in the literature as to what surgical ablation procedure was actually performed. The use of the biatrial lesion set instead of a procedure limited to the left atrium has been shown to be more successful in maintaining sinus rhythm during the longer term, such as what we found in this study in which both the men and the women had a rate of return to sinus rhythm approaching 90%, with 80% off antiarrhythmic medications at 1 year. Both the men and the women in this study also demonstrated an increase in their general quality of life, in which much of the variance of the increase was noted to be an improvement in their reported AF symptom severity and frequency burden. These findings have also been confirmed in a meta-analysis performed by Barnett and Ad.54 Ad,55 in his commentary titled “How Do We Spell Maze: A Dialogue Concerning Definitions and Goals,” discusses that the use of the terms Cox-Maze or maze should only be used when the procedure that was executed was performed exactly as described by Dr James Cox. He goes on to discuss that the success of the procedure should encompass three components: (a) success in restoring rhythm, (b) decreasing the risk for thromboembolic events, and (c) improving the patients’ quality of life.56 All topics were covered in our study and demonstrated how well the women did after the Cox-Maze procedure.
This is a single-center study with highly experienced surgeons performing the Cox-Maze procedure, so these results may not be generalizable to smaller institutions. In addition, the screening process for patients to be referred for surgery may bias our results because only the sicker women may get referred, whereas the healthier women may elect to undergo other treatment options.
The overall study was powered to detect any sex differences with a small to medium effect size. However, the very low rate of observed events for perioperative outcomes presented a statistical limitation. There is a possibility that with a much larger sample size and greater event rates for these outcomes, sex differences may emerge. However, this report represents one of the largest surgical ablation samples from a single center addressing sex and sex differences. Further, studies examining sex differences in outcomes after surgical ablation are necessary to replicate the findings presented before final rejection of the null hypothesis is accepted.
As we have published previously, we recognize that electrocardiogram and 24-hour holter may not be as robust as longer term monitoring; however, this bias would be the same for both men and women, and the monitoring provided meets the Heart Rhythm Society guidelines.19,23 We will continue to lobby for more intensive and consistent follow-up methods so that results between centers can be compared. However, there are limitations with all modes of cardiac monitoring that still need to be overcome.56
This is one of the first studies completed investigating and comparing the outcomes of female and male patients who undergo the Cox-Maze procedure for AF. Similar to other studies published, our findings suggest that women do present for the Cox-Maze procedure sicker than men. However, once treatment was implemented, both the women and the men achieved acceptable outcomes after their surgical procedure. The women experienced the same return to sinus rhythm off antiarrhythmic medications, an improved quality of life, and a decrease in their reported symptoms directly related to AF as captured using an AF symptom frequency and severity tool. No differences in morbidities or survival when compared with men were found. Women and men can expect to have very good outcomes after surgical ablation, such that the Cox-Maze procedure for AF should be considered a safe, effective, and viable treatment option for women.
1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001; 285: 2370–2375.
2. Chugh SS, Blackshear JL, Shen WK, Hammill SC, Gersh BJ. Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol. 2001; 37: 371–378.
3. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004; 110: 1042–1046.
4. Alonso A, Agarwal SK, Soliman EZ, et al. Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2009; 158: 111–117.
5. Prineas RJ, Soliman EZ, Howard G, et al. The sensitivity of the method used to detect atrial fibrillation in population studies affects group-specific prevalence estimates: ethnic and regional distribution of atrial fibrillation in the REGARDS study [published online ahead of print June 27, 2009]. J Epidemiol. 2009; 19: 177–181.
6. Volgman AS, Manankil MF, Mookherjee D, Trohman RG. Women with atrial fibrillation: greater risk, less attention. Gend Med. 2009; 6: 419–432.
7. Wyse DG, Waldo AL, DiMarco JP, et al., for the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002; 347: 1825–1833.
8. Van Gelder IC, Hagens VE, Bosker HA, et al., for the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002; 347: 1834–1840.
9. Rienstra M, Van Veldhuisen DJ, Hagens VE, et al., for the RACE Investigators. Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) study. J Am Coll Cardiol. 2005; 46: 1298–1306.
10. Michelena HI, Powell BD, Brady PA, Friedman PA, Ezekowitz MD. Gender in atrial fibrillation: ten years later. Gend Med. 2010; 7: 206–217.
11. Santangeli P, di Biase L, Pelargonio G, Natale A. Outcome of invasive electrophysiological procedures and gender: are males and females the same? J Cardiovasc Electrophysiol. 2011; 22: 605–612.
12. Simon HU, Sinha AM, Horack M, et al. Abstract 12585: gender and left atrial ablation for atrial fibrillation: outcome data from the German Ablation Registry. Circulation. 2010; 122: A12585
13. Cox JL, Schuessler RB, D’Agostino HJ Jr, et al. The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg. 1991; 101: 569–583.
14. Cox JL, Ad N. New surgical and catheter-based modifications of the Maze procedure. Semin Thorac Cardiovasc Surg. 2000; 12: 68–73.
15. Weimar T, Bailey MS, Watanabe Y, et al. The Cox-maze IV procedure for lone atrial fibrillation: a single center experience in 100 consecutive patients. J Interv Card Electrophysiol. 2011; 31: 47–54.
16. Hunt S, Henry L, Ad N. Using multiple databases to produce comprehensive follow-up in an effort to enhance evaluation of outcome measurements: surgical ablation (Maze) exemplar [published online ahead of print January 19, 2011]. J Healthc Qual. 2011; 33: 50–63.
17. Ad N, Henry L, Hunt S, Stone L. The implementation of a comprehensive clinical protocol improves long-term success after surgical treatment of atrial fibrillation. J Thorac Cardiovasc Surg. 2010; 139: 1146–1152.
18. Ware J, Kosinski M, Turner-Bowker D, et al. How to Score Version 2 of the SF-12 Health Survey. Lincoln, RI: Quality Metric Inc; 2002; .
19. Jenkins LS . Test-Specifications for the Bubien and Kay (Revised Jenkins) Symptom Checklist: Frequency and Severity. Baltimore, MD: University of Maryland Press; 1993; .
20. Bubien RS, Knotts-Dolson SM, Plumb VJ, Kay GN. Effect of radiofrequency catheter ablation on health-related quality of life and activities of daily living in patients with recurrent arrhythmias. Circulation. 1996; 94: 1585–1591.
21. Jenkins LS, Brodsky M, Schron E, et al. Quality of life in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J. 2005; 149: 112–120.
22. Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol. 2000; 36: 1303–1309.
24. Calkins H, Brugada J, Packer DL, et al., for the Heart Rhythm Society; European Heart Rhythm Association; European Cardiac Arrhythmia Society; American College of Cardiology; American Heart Association; The Society of Thoracic Surgeons. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and The Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, The Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace. 2007; 9: 335–379.
25. Ad N, Henry L, Hunt S, Barnett S, Stone L. The Cox-Maze III procedure success rate: comparison by electrocardiogram, 24-hour holter monitoring and long-term monitoring. Ann Thorac Surg. 2009; 88: 101–105.
26. Henry L, Ad N. Long-term monitoring for patients after surgical ablation of atrial fibrillation: are all devices the same? Innovations (Phila). 2010; 5: 259–264.
27. Wolbrette DL. Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. Am J Cardiol. 2003; 91: 39D–44D.
29. Kerr CR, Humphries K. Gender-related differences in atrial fibrillation. J Am Coll Cardiol. 2005; 46: 1307–1308.
30. Paquette M, Roy D, Talajic M, et al. Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation. Am J Cardiol. 2000; 86: 764–768.
31. Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation. 2005; 112: 1687–1691.
32. Roten L, Rimoldi SF, Schwick N, et al. Gender differences in patients referred for atrial fibrillation management to a tertiary center. Pacing Clin Electrophysiol. 2009; 32: 622–626.
33. Reid JM, Dai D, Gubitz GJ, Kapral MK, Christian C, Phillips SJ. Gender differences in stroke examined in a 10-year cohort of patients admitted to a Canadian teaching hospital. Stroke. 2008; 39: 1090–1095.
34. Friberg J, Scharling H, Gadsboll N, Truelsen T, Jensen GB., for the Copenhagen City Heart Study. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study). Am J Cardiol. 2004; 94: 889–894.
35. Forster A, Gass A, Kern R, et al. Gender differences in acute ischemic stroke: etiology, stroke patterns and response to thrombolysis. Stroke. 2009; 40: 2428–2432.
36. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010; 137: 263–272.
37. Ad N, Henry L, Schlauch K, Holmes SD, Hunt S. The CHADS score role in managing anticoagulation after surgical ablation for atrial fibrillation. Ann Thorac Surg. 2010; 90: 1257–1262.
38. Hammond J, Salamonson Y, Davidson P, Everett B, Andrew S. Why do women underestimate the risk of cardiac disease? A literature review. Aust Crit Care. 2007; 20: 53–59.
39. Perelman J, Mateus C, Fernandes A. Gender equity in treatment for cardiac heart disease in Portugal. Soc Sci Med. 2010; 71: 25–29.
40. Patel D, Armaganijan LV, Morillo CA. Atrial fibrillation catheter ablation in females: same hardware, different findings. Expert Rev Cardiovasc Ther. 2011; 9: 1391–1395.
41. Patel D, Mohanty P, Di Biase L, et al. Outcomes and complications of catheter ablation for atrial fibrillation in females. Heart Rhythm. 2010; 7: 167–172.
42. Dagres N, Clague JR, Breithardt G, Borggrefe M. Significant gender-related differences in radiofrequency catheter ablation therapy. J Am Coll Cardiol. 2003; 42: 1103–1107.
43. Forleo GB, Tondo C, De Luca L, et al. Gender-related differences in catheter ablation of atrial fibrillation. Europace. 2007; 9: 613–620.
44. Spragg DD, Dalal D, Cheema A, et al. Complications of catheter ablation for atrial fibrillation: incidence and predictors. J Cardiovasc Electrophysiol. 2008; 19: 627–631.
45. Waller CG. Understanding prehospital delay behavior in acute myocardial infarction in women. Crit Pathw Cardiol. 2006; 5: 228–234.
46. Rosenfeld AG. Treatment-seeking delay among women with acute myocardial infarction: decision trajectories and their predictors. Nurs Res. 2004; 53: 225–236.
47. Harralson TL. Factors influencing delay in seeking treatment for acute ischemic symptoms among lower income, urban women. Heart Lung. 2007; 36: 96–104.
48. Kaul P, Chang WC, Westerhout CM, Graham MM, Armstrong PW. Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes. CMAJ. 2007; 177: 1193–1199.
49. Canto JG, Rogers WJ, Goldberg RJ, et al., for the NRMI Investigators. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA. 2012; 307: 813–822.
50. Conen D, Tedrow UB, Koplan BA, Glynn RJ, Buring JE, Albert CM. Influence of systolic and diastolic blood pressure on the risk of incident atrial fibrillation in women. Circulation. 2009; 119: 2146–2152.
51. Conen D, Ridker PM, Everett BM, et al. A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women [published online ahead of print May 25, 2010]. Eur Heart J. 2010; 31: 1730–1736.
52. Aguado-Romeo MJ, Màrquez-Calderón S, Buzón-Barrera ML., for the Medical Practice Variations Andalusian Group. Hospital mortality in acute coronary syndrome: differences related to gender and use of percutaneous coronary procedures. BMC Health Serv Res. 2007; 7: 110
53. Miyasaka Y, Barnes ME, Gersh BJ, et al. Coronary ischemic events after first atrial fibrillation: risk and survival. Am J Med. 2007; 120: 357–363.
54. Barnett SD, Ad N. Surgical ablation as treatment for the elimination of atrial fibrillation: a meta-analysis. J Thorac Cardiovasc Surg. 2006; 131: 1029–1035.
55. Ad N. How do we spell maze? A dialogue concerning definitions and goals. J Thorac Cardiovasc Surg. 2006; 132: 1253–1255.
56. Ad N. The challenge of defining procedural endpoints for the surgical treatment of atrial fibrillation. Eur J Cardiothorac Surg. 2012; 41: 119–120.
This retrospective review from Dr Henry and her colleagues at the Inova Heart and Vascular Institute examined 540 patients who underwent a Cox-Maze procedure (CMP) at their institution. They examined outcome differences between men and women. They found that after the CMP, there was no difference in return to sinus rhythm, all-cause mortality, and cardiac-related mortality between sexes. They also found similar relief of symptoms and improvement of quality of life. This study collaborates with previous reports that have shown that gender was not a predictor of late atrial fibrillation recurrence (Prasad SM, Maniar HS, Camillo CJ, et al. The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures. J Thorac Cardiovasc Surg. 2003;126:1822–1828; Damiano RJ Jr, Schwartz FH, Bailey MS, et al. The Cox maze IV procedure: predictors of late recurrence. J Thorac Cardiovasc Surg. 2011;141:113–121). This study further revealed that other clinical outcomes were similar for men and women. This work provides support to the widely held concept that the CMP is equally safe and effective for men and women.
Surgical ablation; Gender; Outcomes; Longitudinal follow-up
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