Abstract
Introduction:
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat.
Methods and Results:
Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0–12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence.
Conclusion:
Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.
Keywords: atrial fibrillation, Cox-Maze IV, late outcomes, longstanding persistent atrial fibrillation, surgical ablation
1 |. INTRODUCTION
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with prevalence estimates increasing globally over the last decade.1 Patients with AF have significant morbidity and mortality secondary to symptoms detrimental to quality-of-life, hemodynamic compromise, and embolic stroke.1,2 Many treatment modalities have been used to reduce the global burden of this disease, including antiarrhythmic drugs (AADs), catheter-based ablation, and surgical ablation (SA).
While relatively ubiquitous in clinical practice, medical management with AADs has had poor efficacy and has been associated with significant adverse side effects.3–6 Given advances in percutaneous interventional techniques, catheter-based ablations have been utilized more frequently, and have had excellent success rates, particularly in patients with paroxysmal AF.6 However, even the best outcomes in published series have only shown 52% freedom from AF at 10 years.7 In addition, studies have shown that patients with longstanding persistent AF have had inferior freedom from recurrent atrial tachyarrhythmias (ATAs) when compared to those patients with paroxysmal AF.6–10
The Cox-Maze procedure was introduced in 1987, and was the first successful interventional treatment for AF.11 Since then, a multitude of different surgical techniques have been developed, utilizing a variety of lesion sets and ablation technologies. However, the most-effective SA technique has remained the Cox-Maze procedure.11 While initial “cut-and-sew” iterations of this technique were time-intensive and complex due to need to create multiple incisions in the atrial myocardium, the introduction of bipolar radiofrequency ablation and cryoablation has simplified the procedure significantly.12 This has led to the development of the Cox-Maze IV procedure (CMP-IV).13,14 The CMP-IV has excellent efficacy as shown by our group and others,15–17 with 77% freedom from ATAs at 10 years.18 The late survival benefit associated with concomitant CMP-IV has also been well-established.19 Most importantly, it has sharply reduced both operative times and complication rates, leading to more widespread adoption of surgical ablation, particularly in patients referred for concomitant cardiac surgery.12,19,20
While used most commonly in the setting of other concomitant cardiac surgery (e.g., mitral valve repair or replacement), the Cox-Maze IV has been shown to be efficacious and safe as a stand-alone procedure.21,22 Our group has previously shown equal efficacy of the stand-alone CMP-IV in restoring sinus rhythm (SR) amongst patients with paroxysmal and non-paroxysmal AF at early follow-up. Few studies have described outcomes at late follow-up in sizable cohorts of patients.21–23 This study examined our early-, mid-, and late-term outcomes of the stand-alone CMP-IV amongst 174 consecutive patients with longstanding persistent AF. Longstanding persistent AF was selected for analysis because it is recognized to be the most difficult type of AF to treat and is the most common type of AF referred for surgical ablation.15
2 |. METHODS
This study was approved by the Washington University School of Medicine Institutional Review Board. Informed consent and permission for release of information were obtained from all patients with a waiver of consent. Our institutional Society of Thoracic Surgery (STS) database was used for preoperative demographic data, operative details, and complications using STS definitions. Data pertaining to rhythm follow-up were prospectively entered into our institutional AF outcomes database. Missing data were ascertained through chart review, contact with patients, and from referring physicians as needed.
2.1 |. Patient population
From May 2003 to March 2020, 286 patients underwent elective stand-alone SA. Patients who underwent ablation procedures other than biatrial CMP-IV (n = 18) or who did not have a complete left-sided lesion set (n = 21) were excluded, leaving 247 patients. Of these remaining patients, our analysis was limited to only those who had long-standing persistent AF (n = 174). Roughly half of this final cohort underwent sternotomy as compared to a minimally invasive right mini-thoracotomy (RMT). These operative techniques have been previously described by our group.24
2.2 |. Rhythm follow-up
Patient follow-up was performed with a prospectively-defined schedule at 1, 3, 6, and 12 months, and annually thereafter. At each follow-up visit, patients underwent history and physical evaluations, as well as electrocardiograms (ECGs). Routine prolonged monitoring was initiated in 2006 and included either 24–48 h Holter monitoring, pacemaker interrogation, or implantable loop recording (ILR).
Ninty-one percent of patients (146/161) underwent prolonged monitoring at some point in their follow-up; 76% (109/143), 56% (40/73), and 60% (24/40) of patients underwent prolonged monitoring at 1-, 5-, and 7-year follow-up, respectively. ATA recurrence was defined as any episode of AF, atrial flutter, or atrial tachycardia lasting longer than 30 s, in accordance with the 2017 Heart Rhythm Society (HRS) consensus statement.10 ATA recurrence was examined in two ways. In the stricter of the two methods, we considered any ATA recurrence that occurred greater than 3 months postoperatively to be a permanent failure, regardless of duration of ATA or symptoms. In our second method, we looked at the percent of patients in SR at each time point, such that a patient who, for example, had a brief recurrence of 45 s at 3 years could still be recognized as being ATA-free at 5 years if they were in SR at that time. This method is considered by our group to be more clinically relevant given it takes into account that individual episodes of recurrence can be short and infrequent. This allows for differentiation between, for example, a patient who has multiple prolonged episodes of ATA a day and a patient who has had only one or two 1-min long episodes of ATA over their entire postoperative lifetime. Any patient who required an interventional procedure for rhythm control after the 90-day blanking period was considered a permanent treatment failure.
2.3 |. Perioperative care
Postoperative AADs and anticoagulants were administered to all patients unless contraindicated.18 Patients who experienced postoperative ATAs unresponsive to AADs were cardioverted before discharge unless contraindicated (primary contraindication was documented left atrial [LA] thrombus). AADs were discontinued in patients in SR at 2–3 months postoperatively. Anticoagulants were discontinued at 3–6 months postoperatively for patients who both had no ATAs on prolonged monitoring and no evidence of atrial stasis or thrombus on echocardiography, irrespective of their CHA2DS2-VASc score.25 In the immediate postoperative period patients with persistent junctional or other types of bradycardia were allowed 5–7 days for sinus node recovery. After this time, if patients were symptomatic, a dual chamber pacemaker was inserted. Median follow-up time was 4.0 years (interquartile range [IQR] 1.3–7.5 years). At 1, 5, and 7 years, 94% (135/143), 95% (69/73), and 88% (35/40) of patients available for follow-up had documented rhythm data, respectively.
2.4 |. Postoperative complications
Major complications during the first 30 postoperative days included cerebrovascular accident, mediastinitis, pneumonia, sepsis, renal failure requiring dialysis, intra-aortic balloon pump, or reoperation. A patient was considered to have had a postoperative ATA if they had any episode or either AF or an ATA lasting longer than 30 s during their postoperative hospital stay.
2.5 |. Statistical analysis
Continuous variables were expressed as mean±standard deviation (SD) or as a median with IQR, as appropriate. Student’s t test compared means of normally distributed continuous variables, while Mann–Whitney U test was used for skewed distributions. Categorical variables were expressed as frequencies and percentages with outcomes compared using either χ2 or Fisher’s exact test, as appropriate. A p value <.05 was considered statistically significant.
Freedom from ATAs on/off AADs was calculated at each prospectively defined follow-up timepoint. Composite endpoint survival (freedom from first ATAs recurrence and death) was reported as a Kaplan–Meier estimate and presented alongside the cumulative incidence functions for both ATAs recurrence and death.26 The probability of being both alive and free from any ATAs recurrence (remaining in sinus rhythm for the study duration) was equivalent to the probability of experiencing neither of the competing risks.27 Seventeen clinically relevant variables were evaluated using univariable and multivariable Fine-Gray regression to identify factors associated with ATAs recurrence. Data analysis was performed using SAS Studio 3.8 on SAS 9.4 (SAS Institute Inc.), SPSS version 25 (SPSS Inc.), and R 3.6.3 using the cmprsk package (The R Foundation for Statistical Computing).
3 |. RESULTS
3.1 |. Demographics and preoperative clinical history
The mean age at time of operation in this patient population was 60.1 ± 10.1 years (Table 1). The majority of patients (72%) were male, and all patients were White. Over the entire follow-up period, 24% of patients (36/150) had an ATA recurrence. There were no significant differences in age, sex, or preoperative body mass index (BMI) between groups by rhythm outcome (ATA freedom vs. ever recurrence). There were also no significant differences between groups by rhythm outcome in rates of preoperative BMI ≥ 30, hyperlipidemia, peripheral vascular disease, prior cerebrovascular accident, CHA2DS2-VASc score, hypertension, history of cigarette smoking, chronic lung disease, or diabetes mellitus. No patient had preoperative renal failure. The majority of patients (77%, 134/174) had a CHA2DS2-VASc score greater than or equal to 2, that is, a 2.9% or greater risk of stroke/transient ischemic attack/systemic embolism per year.28
TABLE 1.
Baseline patient characteristics
| Variable | Total study population | Patients free from ATAs | Patients with ATA recurrence | Statistical significance | |
|---|---|---|---|---|---|
| Demographics | Number of patients (% of total population) | 174 | 114 (76%) | 36 (24%) | |
| Mean age (±SD) | 60.1 years (±10.1) (n = 174) | 59.7 years (±9.8) (n = 114) | 61.9 years (±11.0) (n = 36) | p = .2626a | |
| % Male sex | 72% (126/174) | 72% (82/114) | 69% (25/36) | p = .7737b | |
| % White race | 100% (174/174) | ||||
| Preoperative noncardiac clinical history | % Mean BMI (±SD) | 32.0 (±6.8) (n = 174) | 31.9 (±6.8) (n = 114) | 32.1 (±8.0) (n = 36) | p = .8706a |
| % with BMI ≥ 30 | 59% (102/174) | 59% (67/114) | 56% (20/36) | p = .7332a | |
| % with HLD | 55% (95/174) | 55% (63/114) | 61% (22/36) | p = .5370a | |
| % with PVD | 5% (9/174) | 4% (5/114) | 11% (4/36) | p = .2191c | |
| % with prior CVA | 14% (23/161) | 14% (17/125) | 17% (3/36) | p = .6431a | |
| % with CHA2DS2-VASc ≥2 | 77% (134/174) | 76% (87/114) | 75% (27/36) | p = .8720a | |
| % with HTN | 67% (116/174) | 65% (74/114) | 69% (25/36) | p = .6168a | |
| % Ever smokers | 36% (62/174) | 33% (38/114) | 44% (16/36) | p = .2260a | |
| % With chronic lung disease | 10% (17/174) | 9% (10/114) | 14% (5/36) | p = .3556b | |
| % With DM | 14% (25/174) | 14% (16/114) | 14% (5/36) | p = .9824a | |
| % with Renal Failure | 0% (0/174) |
Note: For patients that had follow-up of at least 6 months or longer postoperatively, characteristics were compared across rhythm outcomes. There were no significant differences between groups by freedom from versus recurrence of ATAs for any of these variables (alpha = 0.05).
Abbreviations: ATA, atrial tachyarrhythmia; BMI, body mass index; CVA, cerebrovascular accident; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; PVD, peripheral vascular disease.
Two-way t test with pooled variances.
χ2 test.
Two-sided Fisher’s exact test.
3.2 |. Characterization of preoperative cardiac function and atrial fibrillation
Overall, 4% (7/174) of patients had a history of myocardial infarction, while 85% (148/174) had some degree of congestive heart failure symptoms associated with their AF (Table 2). Mean left ventricular ejection fraction was 54 ± 13%, and 41% (72/174) of patients had New York Heart Association Classes III or IV heart failure.29 There were no significant differences between groups by rhythm outcome for any of these variables.
TABLE 2.
Baseline cardiac function and history
| Variable | Total study population | Patients free from ATAs | Patients with ATA recurrence | Statistical significance | |
|---|---|---|---|---|---|
| General cardiac | % with prior MI | 4% (7/174) | 4% (4/114) | 6% (2/36) | p = .6303b |
| % with CHF | 85% (148/174) | 85% (97/114) | 81% (29/36) | p = .5179a | |
| Mean LVEF (±SD) | 54% (±13.3) (n = 172) | 55% (±13.5) (n = 112) | 54% (±11.6) (n = 36) | p = .6300e | |
| % with NYHA HF Class III or IV | 41% (72/174) | 43% (49/114) | 36% (13/36) | p = .4655a | |
| AF-specific | Median length of time in AF (IQR) | 7.8 years (4.0–12.0) (n = 174) | 7.0 years (3.2–11.0) (n = 114) | 10.0 years (4.9–14.5) (n = 36) | p = .0858c |
| Mean LA diameter (±SD) | 4.8 cm (±1.0) (n = 158) | 4.7 cm (±1.0) (n = 105) | 5.1 cm (±1.0) (n = 35) | p = .0792e | |
| % failed catheter ablation | 71% (124/174) | 69% (79/114) | 75% (27/36) | p = .5124a | |
| Median number of failed catheter ablations (IQR) | 2 (1–3) (n = 124) | 2 (1–3) (n = 79) | 2 (1–2) (n = 27) | p = .7012c | |
| % with pacemaker and/or AICDd | 10% (17/174) | 6% (7/114) | 22% (8/36) | p = 0.0095 b |
Note: For patients that had follow-up of at least 6 months or longer postoperatively, cardiac function and history were compared across postoperative rhythm outcomes. p values are bolded to indicate a significant difference between groups by postoperative ATA status (alpha = 0.05).
Abbreviations: AF, atrial fibrillation; AICD, automatic implantable cardioverter defibrillator; ATA, atrial tachyarrhythmia; CHF, congestive heart failure; HF, heart failure, IQR, interquartile range, LA, left atrium; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.
χ2 test
Two-sided Fisher’s Exact test
Mann–Whitney U test, two-sided normal approximation
Two patients had ICDs (for nonischemic cardiomyopathy and neurocardiogenic syncope, respectively), 14 had pacemakers only, and 1 had no available data on device type.
Two-way t test with pooled variances.
Overall median length of time in AF was 7.8 years (IQR: 4.0–12.0 years), and mean left atrial diameter was 4.8 ± 1.0 cm. The majority of patients (71%, 124/174) had failed at least one prior catheter-based ablation attempt, with a median number of failed attempts of 2 (IQR: 1–3). None of these variables varied significantly between groups by rhythm outcome. Patients who remained ATA-recurrence free over the follow-up period did have a significantly lower rate of preoperative pacemaker or implantable cardioverter defibrillator placement (6% vs. 22%, p = .0095) compared to those who had an ATA recurrence.
3.3 |. Operative characteristics
Roughly half of patients underwent sternotomy (48%), and the rest underwent a minimally invasive RMT (Table 3). Median cardiopulmonary bypass (CPB) time was 152.0 min (IQR: 116.0–178.0), and median aortic cross-clamp time was 55.0 min (IQR: 36.0–68.0). The majority of CMP-IV lesion sets were created using a nonirrigated bipolar radiofrequency ablation clamp (79% 137/173; AtriCure Inc.), with the remainder created using irrigated bipolar radiofrequency devices (Medtronic PLC). Cryoablation was used for all ablations near the tricuspid and mitral valve annuli. There were no significant differences between groups by rhythm outcome in operative approach, ablation device usage, or median CPB or aortic cross-clamp time. Of note, CPB and aortic cross-clamp time were significantly increased in patients who underwent RMT when compared to those who underwent sternotomy (median CPB time 175.0 min, IQR: 155.0–191.0, vs. 116.0 min, IQR: 102.0–134.0, p < .0001; median aortic cross clamp time 67.0 min, IQR 60.0–75.0, vs 36.0 min, IQR 30.0–46.0, p < .0001).
TABLE 3.
Operative characteristics
| Variable | Total study population | Patients free from ATAs | Patients with ATA recurrence | Statistical significance |
|---|---|---|---|---|
| % Sternotomy | 48% (83/174) | 52% (59/114) | 53% (19/36) | p = .9147a |
| Median CPB time (IQR) | 152.0 min (116.0–178.0) (n = 174) | 145.5 min (114.0–179.0) (n = 114) | 150.0 min (114.0–170.0) (n = 36) | p = .9754b |
| Median aortic cross-clamp time (IQR) | 55.0 min (36.0–68.0) (n = 172) | 54.0 min (35.0–67.5) (n = 112) | 53.0 min (36.5–72.0) (n = 36) | p = .7089b |
| % AtriCure ablation device | 79% (137/173) | 81% (91/113) | 67% (24/36) | p = .0843a |
Note: For patients that had follow-up of at least 6 months or longer postoperatively, operative characteristics were compared across postoperative rhythm outcomes. There were no significant differences between groups by freedom from versus recurrence of ATAs for any of these variables (alpha = 0.05).
Abbreviations: ATA, atrial tachyarrhythmia; CPB, cardiopulmonary bypass; IQR, interquartile range.
χ2 test.
Mann–Whitney U test, two-sided normal approximation.
3.4 |. Postoperative characteristics and complications
Patients with ATA recurrence had a significantly longer median postoperative hospital length of stay compared to those without recurrence (8 days [IQR: 7–9.5] vs. 7 days [IQR: 5–10]; Table 4). Patients who remained ATA-recurrence free over the entire follow-up period had significantly shorter median intensive care unit (ICU) length of stay (41 h [IQR: 25–75] vs. 73 h [IQR: 35–101, p = .0090) and shorter median mechanical ventilation time (3 h [IQR: 1–6] vs. 5 h [IQR: 4–16], p = .0003) compared to those who had an ATA recurrence.
TABLE 4.
Postoperative characteristics and complications
| Variable | Total study population | Patients free from ATAs | Patients with ATA recurrence | Statistical significance | |
|---|---|---|---|---|---|
| Median postoperative hospital length of stay (IQR) | 7 days (6–10) (n = 174) | 7 days (5–10) (n = 114) | 8 days (7–9.5) (n = 36) | p = 0.0327 c | |
| Median ICU length of stay (IQR) | 46.0 h (25.5–92.0) (n = 173) | 41.3 h (25.0–75.3) (n = 113) | 72.8 h (34.8–101.0) (n = 36) | p = 0.0090 c | |
| Median mechanical ventilation time (IQR) | 3.6 h (1.5–6.0) (n = 150) | 3.0 h (1.0–6.0) (n = 121) | 5.0 h (3.7–16.0) (n = 29) | p = 0.0003 c | |
| % readmitted within 30 days | 16% (27/174) | 15% (17/114) | 14% (5/36) | p = .8797a | |
| Major 30-day Complications | % requiring reoperation | 1% (2/174) | 1% (1/114) | 0% (0/36) | p = 1.0000b |
| % with PNA | 2.9% (5/174) | 2.6% (3/114) | 2.8% (1/36) | p = 1.0000b | |
| % with sepsis | 0.8% (1/126) | 0% (0/87) | 5.9% (1/17) | p = .1635b | |
| % with renal failure requiring dialysis | 0.7% (1/154) | 0% (0/100) | 0% (0/30) | ||
| % with CVA | 1.7% (3/174) | 2.6% (3/114) | 0% (0/36) | p = 1.0000b | |
| AF-specific | % with pacemaker placed postoperativelyd | 7.5% (13/174) | 7.9% (9/114) | 2.8% (1/36) | p = .4524b |
| % with postoperative ATAse | 40.2% (70/174) | 36.8% (42/114) | 55.6% (20/36) | p = 0.0468 a | |
| % in sinus rhythm at hospital discharge | 78.2% (136/174) | 82.5% (94/114) | 72.2% (26/36) | p = .1808a | |
Note: For patients that had follow-up of at least 6 months or longer postoperatively, postoperative characteristics and complications were compared across postoperative rhythm outcomes. p values are bolded to indicate a significant difference between groups by postoperative ATA status (alpha = 0.05).
Abbreviations: AF, atrial fibrillation; ATA, atrial tachyarrhythmia; CVA, cerebrovascular accident; ICU, intensive care unit; IQR, interquartile range; PNA, pneumonia.
χ2 test
Two-sided Fisher’s exact test
Mann–Whitney U test, two-sided normal approximation
11/13 pacemakers were placed for sick sinus syndrome, 2/13 were placed for complete heart block.
Postoperative ATAs as defined by the Society for Thoracic Surgery as postoperative atrial fibrillation or ATAs during postoperative hospital stay.
Major postoperative complications were low in this population overall (Table 4). There were no mortalities within 30 days of surgery. The overall major complication rate was only 9% (15/174). Two patients required reoperation, one for bleeding and one for sternal dehiscence, and one patient had postoperative sepsis. Five patients developed pneumonia. One patient had postoperative renal failure which transiently required dialysis; no patient required permanent dialysis. Three patients (1.7%) had a cerebrovascular accident (CVA) in the 30 day postoperative period, and one (0.6%) had a late CVA, which occurred 4 years postoperatively. There were no significant differences in rates of major postoperative complications between groups by rhythm outcome. There were no significant differences in rates of major postoperative complications between groups by operative approach, with the overall rate of major complications 11% (9/83) in the sternotomy group versus 7% (6/91) in the RMT group, p = .4195.
The majority of patients were in sinus rhythm at time of hospital discharge (78% 136/174), with 8% (13/174) requiring pacemaker placement at a median of 8.0 days postoperatively (IQR: 7.0–11.0). 85% of those pacemakers (11/13) were placed for sick sinus syndrome, and 15% (2/13) for complete heart block. This was not significantly different between groups by rhythm outcome (Table 4). Patients who remained ATA-recurrence free over the follow-up period were significantly less likely to have had postoperative ATAs during their initial hospital stay (37%, 42/114 vs. 56%, 20/36, p = .0468) compared to those who had an ATA recurrence.
3.5 |. Rhythm follow-up
Overall freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively (Figure 1). Freedom from ATAs and AADs was 87% (111/128), 69% (44/64), and 68% (27/40) at the same time points. At each timepoint, the percentage of patients on warfarin was 23% (30/133), 30% (20/67), and 32% (12/37), respectively. By competing risks analysis to first ATA recurrence, the probability of remaining alive and free of ATAs was estimated to be 91%, 76%, and 63% at follow-up years 1, 5, and 8, respectively (Figure 2 and Table 5). The estimated incidence of first ATA recurrence was 7%, 18%, and 25%, respectively. Estimated mortality at these time points was 2%, 6%, and 12%, respectively. Amongst patients who did have recurrence of ATA, the median number of recurrences was 2 (IQR: 1–3) over the entire follow-up period, with 61% (22/36) of these patients having only 1–2 recurrences.
FIGURE 1.
Seven year follow-up after standalone Cox-Maze IV in patients with longstanding persistent atrial fibrillation, showing freedom from atrial tachyarrhythmia (ATA) recurrence and freedom from both ATA recurrence and antiarrhythmic drugs (AAD) at 1, 3, 5, and 7 years postoperatively with standard error bars
FIGURE 2.
Competing risks of ATAs recurrence (red) and death (green) following stand-alone Cox-Maze IV procedure for longstanding persistent atrial fibrillation are depicted by cumulative incidence functions. ATAs recurrence-free survival (blue) is depicted as a composite endpoint, equivalent to the probability of experiencing neither of the competing risks. ATA, atrial tachyarrhythmias
TABLE 5.
Number at risk by year after standalone Cox-Maze IV and percentage of patients estimated to be in each state
| Year | Number at risk | Alive and free from ATAs recurrence (%) | First documented ATAs recurrence (%) | Death (%) |
|---|---|---|---|---|
| 1 | 139 | 91 | 7 | 2 |
| 2 | 123 | 84 | 13 | 3 |
| 3 | 100 | 81 | 16 | 3 |
| 4 | 86 | 77 | 18 | 5 |
| 5 | 81 | 76 | 18 | 6 |
| 6 | 59 | 72 | 20 | 8 |
| 7 | 48 | 69 | 23 | 8 |
| 8 | 38 | 63 | 25 | 12 |
Note: Patients were assumed to be in one of three mutually exclusive states at each point during follow-up: alive and free from ATAs recurrence (composite endpoint), alive and having experienced first ATAs recurrence (CIF), or dead before ATAs recurrence (CIF).
Abbreviations: ATA, atrial tachyarrhythmia; CIF, cumulative incidence function.
3.6 |. Predictors of ATAs recurrence
Univariable analysis of seventeen preoperative and perioperative variables was performed to evaluate potential predictors of ATAs recurrence (Table 6). On multivariable Fine-Gray regression, increased preoperative duration of AF (SHR 1.92, 95% CI [1.16, 3.17], p = .011) and early postoperative ATAs (SHR 2.06, 95% CI [1.06, 4.00], p = .033) were associated with increased risk of ATAs recurrence. The relationship between AF duration and ATA recurrence is depicted in Figure 3. Despite significance on univariable regression, increased left atrial size was not predictive of future ATAs recurrence on multivariable regression (p = .116). The number of prior catheter ablations was also not a significant predictor of recurrence (p = .325).
TABLE 6.
Univariable and multivariable predictors of first ATAs recurrence by Fine-Gray regression
| Univariable analysis | Multivariable analysis | |||
|---|---|---|---|---|
| Variable | p value | Subdistribution hazard ratio (95% CI) | p value | Subdistribution hazard ratio (95% CI) |
| Age (years) | 0.195 | 1.03 (0.99, 1.07) | ||
| Male sex | 0.517 | 0.80 (0.40, 1.58) | ||
| BMI (kg/m2) | 0.890 | 1.00 (0.97, 1.03) | ||
| Hyperlipidemia | 0.551 | 1.23 (0.62, 2.44) | ||
| Hypertension | 0.610 | 1.20 (0.60, 2.37) | ||
| NYHA class III/IV | 0.870 | 0.95 (0.48, 1.87) | ||
| LVEF (%) | 0.873 | 1.00 (0.98, 1.02) | ||
| CHF | 0.294 | 1.44 (0.73, 2.82) | ||
| Ever smoker | 0.370 | 1.36 (0.69, 2.68) | ||
| Preoperative creatinine | 0.211 | 2.49 (0.60, 10.40) | ||
| Length of time in AF (years) | 0.003 | 1.99 (1.27, 3.12) | 0.011 | 1.92 (1.16, 3.17) |
| LA size (cm) | 0.079 | 1.37 (0.96, 1.94) | 0.116 | 1.32 (0.93, 1.85) |
| Number of prior catheter ablations | 0.325 | 1.13 (0.88, 1.45) | ||
| CPB time (h) | 0.040 | 1.71 (1.02, 2.86) | 0.072 | 1.56 (0.96, 2.53) |
| AtriCure energy device | 0.828 | 0.93 (0.46, 1.86) | ||
| Sternotomy | 0.201 | 0.64 (0.32, 1.27) | ||
| Postoperative ATAsa | 0.034 | 2.04 (1.05, 3.94) | 0.033 | 2.06 (1.06, 4.00) |
Note: p values are bolded to indicate statistical significance.
Abbreviations: AF, atrial fibrillation; ATA, atrial tachyarrhythmia; BMI, body mass index; CI, confidence interval, CHF, congestive heart failure; CPB, cardiopulmonary bypass; LVEF, left ventricular ejection fraction; LA, left atrium; NYHA, New York Heart Association.
Postoperative ATAs as defined by the Society for Thoracic Surgery as postoperative atrial fibrillation or ATAs during postoperative hospital stay.
FIGURE 3.
Estimation of the probability of ATAs recurrence within ten years based on length of time in atrial fibrillation before Cox-Maze IV (red dashed line) with 95% confidence intervals (solid blue lines). ATA, atrial tachyarrhythmias
4 |. DISCUSSION
The Cox-Maze procedure remains the most effective treatment for AF, and has been shown to be effective for both paroxysmal and non-paroxysmal AF.13–15,18 There have been few published reports on the late results of the CMP-IV in patients with longstanding persistent AF, who compose the most common subgroup of patients referred for surgical ablation.12
Our results showed excellent and durable success with the CMP-IV for longstanding persistent AF from early through late follow-up amongst 174 consecutive patients. Freedom from ATAs and freedom from both ATAs and AADs was 88% and 68%, respectively at 7 years postoperatively. This is particularly impressive in this group of difficult-to-treat patients, with a median preoperative duration of AF of 7.8 years and a mean LA diameter of 4.8 cm, the majority of whom (71%, 124/174) had failed one or more catheter ablations. Our findings support the use of surgical ablation as a treatment of symptomatic AF refractory to AADs in patients who have failed or are poor candidates for catheter-based interventions, as recommended by the HRS, STS, and European Cardiac Arrhythmia Society.2,10,30
The late results of the CMP-IV in our population were superior to previous studies published on catheter ablation in longstanding persistent AF.7,8 Within our cohort, ATA-free survival at 5 and 7 years was 83% and 88%, compared with 24% AF-free survival at 10 years in persistent AF patients in one study,7 and just 17% ATAs recurrence-free survival at 5 years after a single catheter ablation in persistent AF patients in another.8 This suggests that the CMP-IV should be considered in lieu of catheter ablation in selected patients at high risk for failure (i.e., large left atrial volume, long duration of preoperative AF).
The late results of the CMP-IV in our population were also superior to other surgical ablation techniques.31,32 At 5 years follow-up, our cohort had a 76% ATA-free survival, compared to one study’s 29% AF-free survival in longstanding persistent AF patients after LAA exclusion, pulmonary vein isolation, and ganglionated plexi ablation32 at the same time point. This supports the use of the full CMP-IV lesion set for surgical ablation in patients with long-standing persistent AF who have failed catheter ablation, especially in light of our low complication rates and lack of operative mortality. There was no significant relationship between the type of ablation device used and freedom from ATA recurrence, though there was a trend toward better late outcomes with dry bipolar radiofrequency clamps.
In comparison to the Cox-Maze III procedure (CMP-III), also known as the “cut-and-sew” maze, our group has found that the CMP-IV has similar efficacy but significantly decreased CPB duration and has lower technical complexity, making the CMP-IV the more practical of the two CMP options.13,18 In fact, very few surgeons in the world still perform a CMP-III due to its lengthy operative times and technical difficulty. Though these two procedures have almost identical lesion patterns, the CMP-IV was introduced by our group in 2002 to differentiate the cut-and-sew techniques from an ablation-assisted procedure. We have previously published that while the CMP-IV and CMP-III have similar rhythm outcomes, the CMP-III has both significantly longer cardiopulmonary bypass times (Lall et al13; citation included in original manuscript submission) and higher complication rates. Finally, the CMP-IV has been the more studied operation, and is the only surgical procedure to have received an FDA indication to treat AF.
The longer CPB and aortic-cross clamp times experienced by RMT patients versus those who underwent sternotomy in this cohort can be attributed to differences in operative steps between the two techniques. In the RMT approach, the patient is placed on CPB before opening of the pericardium. However, despite these longer times we had no mortality and minimal morbidity with this technique. In fact, in a prior study we showed that the RMT approach lowered morbidity and decreased length of stay when compared to a sternotomy approach.33 Moreover, it is our opinion that the excellent late results in this study were obtained due to the bloodless field and excellent visualization provided by CPB. Our laboratory has shown in numerous publications that beating heart ablation is subject to many limitations due to the inability of most technology to create transmural lesions in this setting.34 Thus, there has been no way to recreate a complete Maze lesion set without CPB.
The stand-alone CMP-IV was performed with minimal morbidity and no 30-day mortality, regardless of surgical approach. There was only one late CVA (0.6%). Postoperative pacemaker placement (7.5%, 13/174) was comparable to previously published studies, with 85% of those pacemakers (11/13) placed for sick sinus syndrome, and 15% (2/13) placed for complete heart block.12,22 Patients with ATA recurrence had significantly longer median postoperative hospital length of stay, ICU length of stay, and mechanical ventilation time, compared to those without recurrence. This may have been secondary to differences in patients’ underlying baseline health, but could also indicate that greater stress in the postoperative period contributed to eventual recurrence.
On Fine-Gray multivariable regression, the only two factors predictive of late ATAs recurrence were preoperative length of time in AF and early postoperative ATAs. This is similar to previously published results from both our group and others.15,35,36
Although this study is one of the largest in the literature to report late rhythm outcomes for stand-alone surgical ablation in patients with longstanding persistent AF, it is not without limitations. This study was retrospective and nonrandomized, thus subject to inherent selection bias. All operations were performed at a single institution, with most completed by a single, highly-experienced surgeon (n = 164). This may limit generalizability to other centers. Referral patterns and patient selection may have had an impact on our results. Moreover, sample size may have contributed to the variability of these results and increased risk of type II error. An inherent limitation in the study design was the lack of continuous monitoring on all patients, which can lead to interval censoring and underestimation of ATAs recurrence. However, the majority of patients underwent prolonged monitoring during follow-up, and Fine-Gray regression does not assume non-informative censoring. Moreover, the number of patients both followed longer than 5 years and who had prolonged monitoring is higher than almost all previously published studies. While the majority of patients underwent prolonged monitoring, AF burden was not recorded in the available medical record for most of these patients, precluding a burden-based analysis. Burden calculations are only possible in patients with pacemakers or ILRs, which were present in only a small minority of our patients. We have previously studied the utility of ILR use following CMP-IV, and found that ILR use did not increase ATA detection compared to Holter monitoring or ECG.37 Given this, it is unlikely that increasing available burden data via more liberal use of ILRs would significantly alter our findings.
5 |. CONCLUSION
The stand-alone CMP-IV had superior 5 and 7 year recurrence-free survival rates for patients with longstanding persistent AF compared to published reports of other surgical and catheter-based ablation techniques. The stand-alone CMP-IV was equally effective regardless of surgical approach, or number of previous catheter ablations. There were no mortalities and the incidence of major morbidity was low. On Fine-Gray regression, preoperative time in AF and early postoperative ATAs were predictive of late ATAs recurrence. Based on these findings, we recommend consideration of stand-alone CMP-IV for symptomatic patients with longstanding persistent AF who have failed catheter ablation or are poor candidates for catheter-based therapies.
ACKNOWLEDGMENTS
This study was supported by the National Institutes of Health RO1-HL032257 to Ralph J. Damiano, and Richard B. Schuessler, T32-HL007776 to Ralph J. Damiano, Martha M.O. McGilvray, and Meghan O. Kelly, and the Barnes-Jewish Foundation.
DISCLOSURE
R.J.D. - AtriCure, Inc: Speaker and receives research funding; Medtronic: Consultant. Other authors have nothing to disclose.
Funding information
Foundation for Barnes-Jewish Hospital; National Institutes of Health, Grant/Award Numbers: R01-HL032257, T32-HL007776
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1.Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141:E139–E596. [DOI] [PubMed] [Google Scholar]
- 2.Badhwar V, Rankin JS, Damiano RJ Jr., et al. The Society of Thoracic Surgeons 2017 clinical practice guidelines for the surgical treatment of atrial fibrillation. Ann Thorac Surg. 2017;103:329–341. 10.1016/j.athoracsur.2016.10.076 [DOI] [PubMed] [Google Scholar]
- 3.Singh SN, Singh BN, Reda DJ, et al. Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]). Am J Cardiol. 2003;92:468–472. [DOI] [PubMed] [Google Scholar]
- 4.Doyle JF, Ho KM. Benefits and risks of long-term amiodarone therapy for persistent atrial fibrillation: a meta-analysis. Mayo Clin Proc. 2009;84:234–242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Andrade JG, Wells GA, Deyell MW, et al. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021;384:305–315. [DOI] [PubMed] [Google Scholar]
- 6.Bonanno C, Paccanaro M, La Vecchia L, Ometto R, Fontanelli A. Efficacy and safety of catheter ablation versus antiarrhythmic drugs for atrial fibrillation: a meta-analysis of randomized trials. J Cardiovasc Med. 2010;11:408–418. [DOI] [PubMed] [Google Scholar]
- 7.Gaita F, Scaglione M, Battaglia A, et al. Very long-term outcome following transcatheter ablation of atrial fibrillation. Are results maintained after 10 years of follow up? Europace. 2018; 20:443–450. [DOI] [PubMed] [Google Scholar]
- 8.Scherr D, Khairy P, Miyazaki S, et al. Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint. Circ Arrhythm Electrophysiol. 2015;8:18–24. [DOI] [PubMed] [Google Scholar]
- 9.Ganesan AN, Shipp NJ, Brooks AG, et al. Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2:e004549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Calkins H, Hindricks G, Cappato R, et al. HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2017;20:e1–e160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.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. [PubMed] [Google Scholar]
- 12.Weimar T, Schena S, Bailey MS, et al. The cox-maze procedure for lone atrial fibrillation: a single-center experience over 2 decades. Circ Arrhythm Electrophysiol. 2012;5:8–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lall SC, Melby SJ, Voeller RK, et al. The effect of ablation technology on surgical outcomes after the Cox-maze procedure: a propensity analysis. J Thorac Cardiovasc Surg. 2007;133:389–396. 10.1016/j.jtcvs.2006.10.009 [DOI] [PubMed] [Google Scholar]
- 14.Gaynor SL, Diodato MD, Prasad SM, et al. A prospective, single-center clinical trial of a modified Cox maze procedure with bipolar radiofrequency ablation. J Thorac Cardiovasc Surg. 2004;128:535–542. 10.1016/j.jtcvs.2004.02.044 [DOI] [PubMed] [Google Scholar]
- 15.Henn MC, Lancaster TS, Miller JR, et al. Late outcomes after the Cox maze IV procedure for atrial fibrillation. J Thorac Cardiovasc Surg. 2015;150:1168–1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Ad N, Holmes SD, Massimiano PS, Rongione AJ, Fornaresio LM. Long-term outcome following concomitant mitral valve surgery and Cox maze procedure for atrial fibrillation. J Thorac Cardiovasc Surg. 2018;155:983–994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Wu C-C, Chang J-P, Chen M-C, Cheng C-I, Chung W-J. Long-term results of radiofrequency maze procedure for persistent atrial fibrillation with concomitant mitral surgery. J Thorac Dis. 2017;9: 5176–5183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Khiabani AJ, MacGregor RM, Bakir NH, et al. The long-term outcomes and durability of the Cox-Maze IV procedure for atrial fibrillation. J Thorac Cardiovasc Surg. 2020. 10.1016/j.jtcvs.2020.04.100 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Musharbash FN, Schill MR, Sinn LA, et al. Performance of the Cox-maze IV procedure is associated with improved long-term survival in patients with atrial fibrillation undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2018;155:159–170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kneeland PP, Fang MC. Trends in catheter ablation for atrial fibrillation in the United States. J Hosp Med. 2009;4:E1–E5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Ad N, Henry L, Friehling T, Wish M, Holmes SD. Minimally invasive stand-alone Cox-maze procedure for patients with nonparoxysmal atrial fibrillation. Ann Thorac Surg. 2013;96:792–798. [DOI] [PubMed] [Google Scholar]
- 22.Ad N, Holmes SD, Friehling T. Minimally invasive stand-alone Cox Maze procedure for persistent and long-standing persistent atrial fibrillation: perioperative safety and 5-year outcomes. Circ Arrhythm Electrophysiol. 2017;10:10. 10.1161/CIRCEP.117.005352 [DOI] [PubMed] [Google Scholar]
- 23.Lapenna E, De Bonis M, Giambuzzi I, et al. Long-term outcomes of atand-alone Maze IV for persistent or long-standing persistent atrial fibrillation. Ann Thorac Surg. 2020;109:124–131. [DOI] [PubMed] [Google Scholar]
- 24.MacGregor RM, Khiabani AJ, Damiano RJ. The surgical treatment of atrial fibrillation via median sternotomy. Operative Techniques Thorac Cardiovasc Surg. 2019;24:19–37. [Google Scholar]
- 25.Pet M, Robertson JO, Bailey M, et al. The impact of CHADS2 score on late stroke after the Cox maze procedure. J Thorac Cardiovasc Surg. 2013;146:85–89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation. 2016;133:601–609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Huebner M, Wolkewitz M, Enriquez-Sarano M, Schumacher M. Competing risks need to be considered in survival analysis models for cardiovascular outcomes. J Thorac Cardiovasc Surg. 2017;153:1427–1431. [DOI] [PubMed] [Google Scholar]
- 28.Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33:1500–1510. [DOI] [PubMed] [Google Scholar]
- 29.Levin R, Dolgin M, Fox C, Gorlin R. The Criteria Committee of the New York Heart Association: nomenclature and criteria for diagnosis of diseases of the heart and great vessels. LWW Handbooks. 1994;9:344. [Google Scholar]
- 30.January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071–2104. [DOI] [PubMed] [Google Scholar]
- 31.Saini A, Hu YL, Kasirajan V, et al. Long-term outcomes of minimally invasive surgical ablation for atrial fibrillation: a single-center experience. Heart Rhythm. 2017;14:1281–1288. [DOI] [PubMed] [Google Scholar]
- 32.Zheng S, Li Y, Han J, et al. Long-term results of a minimally invasive surgical pulmonary vein isolation and ganglionic plexi ablation for atrial fibrillation. PLOS One. 2013;8:e79755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Lawrance CP, Henn MC, Miller JR, et al. A minimally invasive Cox maze IV procedure is as effective as sternotomy while decreasing major morbidity and hospital stay. J Thorac Cardiovasc Surg. 2014;148:955–962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Schuessler RB, Lee AM, Melby SJ, et al. Animal studies of epicardial atrial ablation. Heart Rhythm. 2009;6:S41–S45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.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. [DOI] [PubMed] [Google Scholar]
- 36.McCarthy PM, Gillinov AM, Castle L, Chung M, Cosgrove D 3rd. The Cox-Maze procedure: the Cleveland Clinic experience. Semin Thorac Cardiovasc Surg. 2000;12:25–29. [DOI] [PubMed] [Google Scholar]
- 37.Damiano RJ Jr., Lawrance CP, Saint LL, et al. Detection of atrial fibrillation after surgical ablation: conventional versus continuous monitoring. Ann Thorac Surg. 2016;101:42–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.