Author + information
- Received April 26, 2016
- Revision received September 28, 2016
- Accepted October 20, 2016
- Published online April 17, 2017.
- David C. Kress, MDa,
- Lynn Erickson, MSa,
- Indrajit Choudhuri, MDa,
- Jodi Zilinski, MDa,
- Tadele Mengesha, MSb,
- David Krum, MSb and
- Jasbir Sra, MDa,∗ ()
- aAurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medical Centers, Milwaukee, Wisconsin
- bAurora Research Institute, Aurora Sinai/Aurora St. Luke’s Medical Centers, Milwaukee, Wisconsin
- ↵∗Address for correspondence:
Dr. Jasbir Sra, Aurora Cardiovascular Services POB, Aurora St. Luke’s Medical Center, 2801 West Kinnickinnic River Parkway, Suite 840, Milwaukee, Wisconsin 53215.
Objectives The outcomes of hybrid ablation versus endocardial catheter ablation alone were evaluated in patients with persistent and long-standing persistent atrial fibrillation (AF).
Background Variable outcomes exist following endocardial catheter ablation in medically refractory patients with persistent AF. A hybrid epicardial−endocardial approach has emerged as an alternative to endocardial ablation.
Methods In 133 consecutive patients, 69 received endocardial ablation alone (pulmonary vein isolation and radiofrequency catheter ablation [endo group]) and 64 received endocardial catheter ablation and epicardial ablation (hybrid group). Recurrence was defined as any arrhythmia following the 3-month blanking period.
Results Patients were followed for a median of 16 months. The hybrid and endo groups were similar in age (61 ± 10 years vs. 62 ± 8 years), body mass index (35 ± 6 kg/m2 vs. 35 ± 7 kg/m2), CHA2D2-VASc score (2 ± 1 vs. 2 ± 1), and ejection fraction (54 ± 11% vs. 53 ± 8%). The hybrid group had longer AF duration (median [interquartile range (IQR)] (12 months [IQR: 8 to 28 months] vs. 7 months [IQR: 5 to 12 months]; p < 0.001) and more previous ablations (58% vs. 25%; p < 0.001). Both groups had similar antiarrhythmic drug use at follow-up (55% vs. 48%). The hybrid group was less likely to have recurrence (37% vs. 58%; p = 0.013) and repeat ablation (9% vs. 26%; p = 0.012), and had an AF-free survival of 72% versus 51% (p = 0.01).
Conclusions Among patients with persistent AF, hybrid ablation is associated with less AF recurrence and fewer re-do ablations. Prospective large-scale randomized trials are needed to validate these results.
Patients with paroxysmal AF can oftentimes be treated with pulmonary vein isolation (PVI) alone (4). Patients with persistent or long-standing persistent AF who are intolerant to class I and III antiarrhythmic drugs (AADs) often require endocardial catheter ablation, which in addition to PVI, can include radiofrequency catheter ablation (RFA) of fractionated electrograms and linear lesions (5). Reported success rates for these procedures vary, but the rates are usually much lower compared with patients with paroxysmal AF (6–8). Enlarged left atria, which are often associated with persistent or long-standing persistent AF, may form the electrophysiologic substrate needed to maintain this arrhythmia. The posterior left atrial (LA) wall is a common target area for ablation in these patients (9).
A surgical method to modify the substrate via atrial debulking has been attempted (10). However, there is no mapping available for patients who may have atrial tachycardia (AT) and atrial flutter (AFL) after initial ablation. Furthermore, the FAST (Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment) trial (11) compared the efficacy and safety of surgical ablation versus catheter ablation and found that although surgical ablation had a higher success at 12 months, adverse events were significantly higher in the surgical ablation group. An epicardial approach combined with endocardial ablation is an option for challenging AF cases. This procedure, referred to as the convergent, or hybrid, procedure, uses minimally invasive ablation of the posterior surface of the LA, with an epicardial approach using endoscopically-guided delivery of lesions (12).
There are few data in the literature that compare outcomes of the hybrid procedure in patients in persistent AF versus conventional endocardial ablation−only RFA.
We sought to compare the success rate of the hybrid procedure at our center with that of an endocardial ablation−only approach for patients with persistent or long-standing persistent AF. Success was defined as no recurrence of atrial arrhythmia after the 3-month blanking period at the patient’s last follow-up appointment.
Patients underwent surgical hybrid ablation on the basis of failed previous ablation, enlarged atria, and/or patient preference for the hybrid procedure. Procedure and follow-up data from consecutive patients, of whom 64 received hybrid ablation and 69 received conventional endocardial ablations, were collected retrospectively from electronic medical records.
All data collected for the study were from patients with persistent or long-standing persistent AF as defined in the Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society (HRS/EHRA/ECAS) Consensus Report (13). Data from the hybrid group were collected from June 9, 2010 to August 20, 2014 in a consecutive fashion. Similarly, data collection from the endocardial ablation patients started on June 28, 2011 and ended on August 21, 2014. Baseline characteristics are summarized in Table 1.
Patients who underwent the hybrid procedure had epicardial ablation concomitant with endocardial ablation, as described in the following. All patients were brought to the electrophysiology operating room, and general endotracheal anesthesia was induced. Hemodynamic monitoring was performed throughout the procedure using arterial line blood pressure monitoring. Transesophageal echocardiography (TEE) was performed to exclude thrombus in the LA appendage.
The hybrid group underwent epicardial ablation of the posterior LA wall using a transabdominal endoscopic approach followed by endocardial catheter ablation as described in the following. A 2-cm incision was placed in the upper midline, the linea alba was divided, the peritoneum was opened, and a 12-mm port was placed. Left and right 5-mm ports were placed for instruments and carbon dioxide insufflation. A 2-cm opening in the central tendon of the diaphragm was made 1 cm anterior to the liver and 2 cm to the left of the inferior vena cava. A Silastic (Dow Corning Corp., Auburn, Michigan) 30-cm pericardioscope was placed through this opening and guided into the oblique sinus with a 6.5-mm scope. Under fluoroscopic guidance, an esophageal temperature probe was passed to lie in the region of the ablation probe.
A pre-ablation epicardial map of the posterior LA and proximal pulmonary vein (PV) trunks was created using the CARTO 3D mapping system (Biosense Webster, South Diamond Bar, California) under direct visualization. Each lesion was delivered with a 3-cm Numeris probe (nContact, Morrisville, North Carolina), which was saline-irrigated and vacuum-attached, at 30 W for 90 s. All lesions were delivered with cold saline infusion within the pericardial sac. Lesions were repeated to achieve 2,700 J delivery, if necessary. Esophageal temperature was monitored to avoid an increase of >0.5°C during any lesion. The entire posterior LA from the right PV trunk to the left PV trunk was ablated with 2 rows of parallel overlapping lesions. The anterior left inferior PV trunk was ablated. Lesions were placed in the recess between the inferior vena cava and right inferior PV in some patients. A new acquisition of voltage signals was done to create a post-epicardial ablation voltage map (Figure 1). A 19-mm BLAKE drain (Ethicon, Somerville, New Jersey) was placed into the pericardial cavity. The abdominal incisions were closed in a standard fashion.
After obtaining venous access, a 20-pole diagnostic catheter (St. Jude Medical, Minnetonka, Minnesota) was advanced under fluoroscopic guidance into the coronary sinus. Diagnostic quadripolar catheters were positioned at the right atrial appendage and His bundle positions. Upon completion of all sheath insertions, 5,000 U of heparin was given. An additional 5,000 U was given via the transseptal sheath after puncture. During the catheter ablation procedure, infusion of heparin was maintained to achieve an activated clotting time of 300 to 350 s.
Fluoroscopy and TEE were performed to guide the Preface sheath (Medtronic, Minneapolis, Minnesota) for transseptal puncture in all but 2 cases. Intracardiac echocardiography was used to guide the Preface sheath in 2 patients. An esophageal probe was placed to monitor temperature throughout the entire endocardial ablation procedure.
Using the CARTO 3D mapping system, maps of the atria were created for identifying fractionated electrograms and any ATs and AFLs.
PVI was performed using conventional catheter ablation or the cryoballoon (Medtronic). Subsequently, RFA was used to ablate complex fractionated atrial electrograms (CFAEs) and/or linear lesions in all but 3 patients. One patient converted to sinus rhythm during epicardial ablation, and after an electrophysiological study, no further ablation was warranted. Another patient converted to sinus rhythm during cryoablation and was found to have no CFAEs or additional tachycardia, and 1 patient experienced tamponade before endocardial ablation, and the procedure was terminated.
RFA for PVI
In the first 24 patients, RFA was used to isolate PVs. After TEE and transseptal puncture, either the Constellation Full Contact Mapping catheter (Boston Scientific, Marlborough, Massachusetts) or a 4-mm deflectable, irrigated-tip ThermoCool ablation catheter (Biosense Webster) was advanced into the LA following fluoroscopic guidance. The ablation catheter was placed in the PVs, and the veins were electrically isolated. Isolation of the PVs was confirmed with a mapping and ablation catheter. A circular mapping catheter was not used to confirm isolation.
Cryoablation for PVI
The Arctic Front or Arctic Front Advance cryoballoon (Medtronic) was used for cryoablation (Table 2). All patients had the 28-mm cryoballoon catheter except 1, in whom a 23-mm catheter was used. Multiple fluoroscopic evaluations were performed with the balloon inflated, and a 50% mixture of contrast and saline was injected into the PV to ensure a complete seal. Subsequently, cryoablation freezing was performed for a total of 3 to 4 min at each PV. During cryoablation, the esophageal and balloon temperatures were monitored. Right phrenic nerve pacing at 1,500 ms was performed with a quadripolar electrophysiology catheter in the superior vena cava during application on the right PV. Diaphragmatic contraction was monitored manually and visually. Isolation of the PVs was confirmed with a mapping and ablation catheter.
RFA for endocardial ablation of CFAEs and linear lesions
RFA for CFAEs and/or linear lesions was performed following PVI in all but 3 patients. Using a stepwise approach, CFAEs were mapped and ablated using RFA. If AF persisted following CFAE ablation, linear lesions involving the LA roofline and mitral isthmus line were created. Conduction block was attempted in all linear lesions and confirmed during pacing from the LA appendage for both the mitral isthmus and rooflines (14). If AT or AFL developed at any point during the ablation procedure, mapping and ablation of the AT and/or AFL was performed. For all patients, if tachycardia persisted following delivery of all lesions, patients were converted to sinus rhythm using intravenous infusion of ibutilide (1 mg over 10 min) and/or direct-current cardioversion (DCCV). Heparin was partially reversed with protamine after the procedure.
Patient follow-up was conducted as recommended by the HRS/EHRA/ECAS Consensus Report (13) and was part of the standard of care. Patients with early recurrences, as defined by any tachycardia within the 3-month blanking period, had a change in AADs or underwent DCCV unless another intervention was performed based on patient history (e.g., number of previous ablations and LA size). Patients who did not respond to DCCV for early recurrence of AF had either a change in AADs, repeat ablation, or atrioventricular junction (AVJ) ablation and/or permanent pacemaker implantation. Data related to procedure complications occurring within 30 days of ablation, as defined by the HRS/EHRA/ECAS Consensus Report (13), were collected. Cardiac symptom data and need for AAD medication were collected for each patient follow-up visit. For each follow-up, detectable AF, AFL, and/or AT was evaluated with a minimum of a 30-s electrocardiographic recording or rhythm strip, or ambulatory monitoring, including pacemaker interrogation, loop recorder, ambulatory cardiac telemetry monitor, or Holter monitor. Timing and distribution of a nonambulatory rhythm strip or electrocardiographic monitoring and ambulatory monitoring were based on standard-of-care visits at approximately 3-month intervals for the first year, followed by 6-month intervals thereafter (Figure 2). Recurrence was defined as documented AF, AFL, or AT that occurred after the 3-month blanking period, a DCCV after the 3-month blanking period, or a repeat ablation or AVJ and/or permanent pacemaker ablation at any time.
Data were entered into a database. Clinical characteristics are presented as frequency (percentage) for categorical variables and mean ± SD and median (interquartile range [IQR]) for continuous variables. Comparisons of clinical characteristics for patients who underwent endocardial ablation or hybrid ablation were made using chi-square or Fisher exact tests for categorical variables and the Wilcoxon rank-sum test for continuous variables (15). A case-control matched analysis was used to reduce selection bias to evaluate recurrence events over time. Thus, the significant difference in baseline characteristics, including duration of persistent AF and previous ablation, was adjusted using 1:1 propensity score matching techniques (16). To evaluate the recurrence event over time between hybrid ablation versus endocardial ablation, only Kaplan-Meier analysis was used for the matched population. The equality over strata was tested by the log-rank test (17). All tests were 2-sided with a p value <0.05 considered to be significant. Analysis was performed using SAS version 9.4 software (SAS Institute, Cary, North Carolina). The last follow-up visit documented was used for analysis.
Procedural data results are outlined in Table 2. Epicardial ablation was performed by the same surgeon for all subjects. The endocardial procedure was performed by various operators, all trained under the same program at our center. Cryoballoon ablation was used to isolate the PVs in 97 of 133 patients (72.9%). Patients who did not receive cryoballoon ablation received PVI using RFA as indicated in the Methods section. There was no significant difference overall in the number of linear lesions performed in either group, but the hybrid group did receive significantly fewer LA roofline lesions than the endocardial ablation group (37 [58%] vs. 55 [80%]; p = 0.01) (data not shown in Table 2). The endocardial ablation−only group required cardioversion significantly more times than the hybrid group to restore sinus rhythm at the end of the procedure (51 [74%] vs. 32 [52%]; p = 0.004). Total procedure time was significantly longer in the hybrid group (313.7 ± 60.8 min vs. 233.1 ± 53.1 min; p < 0.001). The hybrid group had a longer length of stay in the hospital (3.1 ± 1.9 days vs. 1.9 ± 1.1 days; p < 0.001). Dofetilide and amiodarone were the predominant AADs used at discharge in 68 (51%) and 47 (35%) of 133 patients, respectively (data not shown in Table 2).
Complications that occurred within 30 days of the procedure were evaluated based on the HRS/EHRA/ECAS Consensus Guidelines (13) and are summarized in Table 2. There were no significant differences in the number of major complications between the 2 groups. Major and minor complications are described in the following.
Momentary reversible phrenic nerve paralysis was experienced by 3 patients in the hybrid group during the endocardial cryoablation portion of the procedure, but it quickly resolved when cryoablation was terminated. Late tamponade that required pericardiocentesis 25 days after the procedure occurred in 1 patient in the hybrid group. Two patients in the hybrid group had puncture site complications that required surgical intervention. One of these received a right femoral embolectomy 8 days after the procedure, and the other had a pseudoaneurysm at the introducer site that required thrombin injection after the procedure.
One patient in the hybrid group presented with an acute embolic right posterior cerebral artery stroke on day 2 after the procedure. Right posterior cerebral artery intra-arterial tissue plasminogen activator was administered by an interventional neuroradiologist within 2 h of the onset of symptoms, with complete resolution of left hemiparesis and partial improvement of left hemianopia.
One death, caused by a gastrointestinal bleed, occurred approximately 2 weeks after the procedure. The patient was on warfarin at that time.
Endocardial ablation group
Early tamponade occurred in 2 endocardial ablation patients. In the first patient, the procedure was aborted immediately; therefore, only the left superior PV was isolated during the procedure, and no RFA or additional cryoablation was performed. This patient was successfully treated with a pericardial pigtail drain, with no subsequent accumulation of blood. The second tamponade occurred during ablation of the LA roofline and after the patient had received cryoablation. Pericardiocentesis and drainage were performed. Anticoagulation was aborted, and the patient experienced a transient ischemic attack before discharge with complete resolution of symptoms.
Overall, momentary, reversible phrenic nerve paralysis occurred in 4 patients (3%) (data not shown in Table 2) and was noted as a minor complication resulting from use of the cryoballoon.
Ambulatory monitoring was used in 24.2% of patients. Average follow-up was significantly longer in the endocardial ablation group versus the hybrid group. All patients were followed for a minimum of 6 months (median: 16 months; IQR: 12 to 24 months) (Table 2). Interventions for arrhythmia recurrences were similar between the groups, with the exception of the rate of repeat ablation, which was significantly greater in the endocardial ablation group (p = 0.012). These interventions are summarized in Table 2 and outlined in the following. Although not significant, the hybrid group had fewer incidences of AVJ ablation than the endocardial ablation group. The hybrid group required significantly fewer repeat ablations (p = 0.012). Of the 6 patients in the hybrid group who underwent repeat ablation, DCCV failed in 2 before the ablation attempt. Of the 18 repeat ablations in the endocardial ablation group, 9 had no other intervention at follow-up. Two of the endocardial ablation group patients received AVJ ablation after the repeat ablations, as described previously. Four of the repeat ablations in the endocardial group were hybrid ablations. There was no significant difference between the rates of DCCV after the procedures between the hybrid and endocardial ablation groups. Early recurrence of AF that required DCCV occurred in 2 patients from each group; therefore, these were not considered recurrences. There was a significant difference in AF-free survival rate at 16 months and the number of patients who had a recurrence of arrhythmia at their follow-up visit (Figure 3). The hybrid ablation group had a significantly lower recurring arrhythmia rate after the blanking period (36.5% vs. 57.9%; p = 0.013). Patients who received hybrid ablation also had a significantly greater AF-free survival rate at 16 months (72%) compared with those in the endocardial ablation-only group (51%) (p = 0.01) (Figure 3). There were no significant differences in cardiac symptoms between the groups (Table 2).
In this study, we sought to retrospectively evaluate the success rates of hybrid ablation and conventional endocardial RFA at our center.
Male sex, hypertension, and diabetes mellitus each have been associated with a higher risk of AF (18,19). Therefore, it is not surprising that, overall, the cohort was largely male (82.7%), with 68.4% having hypertension at their baseline visit. The hybrid group had a significantly longer duration of AF at baseline and a significantly greater number of previous ablations. Therefore, it is possible that the hybrid population in this study posed a greater challenge for achieving success.
Although there was no significant overall difference in the number of linear lesions performed between the 2 groups, the hybrid group had significantly fewer LA roofline lesions applied during the procedure than the endocardial group. Not surprisingly, the length of stay for the hybrid procedure was significantly longer than that for the endocardial ablation. However, even with a greater length of stay, cost-effectiveness might have still been achieved in this study using the hybrid ablation in a challenging population due to lower recurrence rates and a lesser need for repeat ablation after the procedure (20).
Complication rates for both hybrid and RFA procedures have been reported as 6% (19,21). We reported a 7.8% and 2.9% complication rate for hybrid and endocardial ablation, respectively. A meta-analysis of 23 previous studies that looked at the outcomes of cryoballoon ablation found that phrenic nerve paralysis was the most prevalent complication (4.7%). The analysis also found that this was almost always reversible, with only 0.37% of patients still having paralysis after 12 months (22). Overall, the reversible phrenic nerve complication rate in this study was 3%, which is comparable to the current literature. The paralysis was quickly resolved during the procedure, once the cryoballoon ablation was aborted in all cases. A worldwide survey of AF ablation reported a 1.2% complication rate from cardiac tamponade during AF ablation (21). Similarly, tamponade due to pericardial effusion was seen in 1 hybrid patient and 2 endocardial group patients in our study. Vascular complications are the most common complications in the AF procedure (13). The published rate of groin complications for ablation procedures varies widely. In our study, 3.1% of patients from the hybrid group and no patients in the endocardial ablation group had groin complications.
Pison et al. (23) reported an arrhythmia-free success rate for hybrid ablation of 87% off of AADs for a mixed population of patients with paroxysmal AF, persistent AF, and long-standing persistent AF. Gehi et al. (24) reported a 66.3% success rate for patients with persistent and long-standing persistent AF using a hybrid approach, with 37% of patients still on AAD therapy at 12 months, which is similar to our center’s hybrid success rate of 72% in this study. In a meta-analysis that studied the mean rate for single-procedure, drug-free success of endocardial substrate ablation, the success rate was reported as 47% (25). This rate was similar to our single-procedure success rate of 51%, although 48% of our patients were on AADs at their follow-up visit.
The hybrid group had a significantly lower rate of recurrence of arrhythmia at follow-up and a longer time to recurrence, as seen in the Kaplan-Meier curve in Figure 3, even after matching the populations for the number of previous ablations and duration of AF. The patients in the hybrid ablation group also had significantly fewer repeat ablations for AF, AFL, and/or AT than the endocardial ablation patients. These findings were significant because most predictors of poor outcome, including LA enlargement (26–28) and persistent and/or long-standing persistent AF status (29), were statistically similar between the 2 groups, which indicated that the hybrid procedure yielded better outcomes when predictors of poor outcome were controlled scientifically. Furthermore, hybrid patients in this study had a significantly longer duration of AF before the procedure and a greater number of previous ablations, suggesting they might have been at greater risk for recurrence and a more challenging population.
There were no significant differences at follow-up between the hybrid and endocardial-ablation−only groups with regard to either need for AAD or cardiac symptoms. Therefore, it can be concluded that although this hybrid group was a more challenging population due to longer baseline AF duration and more previous ablations, outcomes still remained better with a lower recurrence rate and a longer time to recurrence, as well as a lower need for repeat ablation.
Data were collected retrospectively. Upon follow-up, patients had various methods of rhythm detection, and the higher incidence of ambulatory monitoring in the endocardial arm might have led to an increased detection of AF in this group. A prospective, randomized approach with consistent use of implantable arrhythmia monitoring is needed to conclude that the hybrid procedure has a significant impact on AF recurrence rates in patients with persistent and long-standing persistent AF.
These findings suggest that the hybrid procedure has a higher success rate shown by significantly fewer incidences of arrhythmia recurrence at follow-up and less need for repeat ablation, as well as a longer time to recurrence. Although a more invasive hybrid procedure resulted in a longer length of stay, the major complication rate between the 2 groups was similar. The significantly lower rate of arrhythmias and time to recurrence, as well as a lesser need for repeat ablation, might justify the need for a longer length of stay for the hybrid ablation in this study.
COMPETENCY IN MEDICAL KNOWLEDGE: Medically refractory patients with persistent and long-standing persistent AF are a challenging population to treat, and these patients may benefit from epicardial ablation of the posterior left atrial wall followed by endocardial ablation, in which arrhythmias can be mapped and ablated.
TRANSLATIONAL OUTLOOK: Additional studies, including prospective randomized trials, are needed to effectively compare the epicardial-endocardial hybrid ablation approach with current standard endocardial ablation approaches in patients with persistent and long-standing persistent AF.
The authors gratefully acknowledge Jennifer Pfaff and Susan Nord of Aurora Cardiovascular Services for editorial preparation of the manuscript, and Brian Miller and Brian Schurrer or Aurora Research Institute for assistance with the figures.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- antiarrhythmic drug
- atrial fibrillation
- atrial flutter
- atrial tachycardia
- atrioventricular junction
- complex fractionated atrial electrograms
- direct-current cardioversion
- left atrium/left atrial
- pulmonary vein
- pulmonary vein isolation
- radiofrequency ablation
- transesophageal echocardiography
- Received April 26, 2016.
- Revision received September 28, 2016.
- Accepted October 20, 2016.
- 2017 American College of Cardiology Foundation
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