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Transvenous before surgical hybrid procedure.


Atrial fibrillation (AF) is the most common chronic arrhythmia requiring treatment in Western society and has become a major health burden. The risk of developing AF from age 40-95 is 26% in men and 23% in women. (1) In the ATRIA study it was estimated that 2.3 million adults in the U.S. had AF in 2006 and 2007 and that this will increase to 5.6-7.56 million by the year 2050. (2,3) Unfortunately, medical management with either rate or rhythm control has yielded suboptimal clinical results leading to further development and advancement of non-pharmacological strategies, including both surgical and endovascular ablations. For patients with documented paroxysmal AF (PAF), catheterbased pulmonary veins isolation has resulted in acceptable results, but long-term success remains disappointing for patients with persistent and long-standing persistent atrial fibrillation. (4) This has led to further refinements in non-pulmonary vein targets including ganglionated plexi, ectopic foci, rotors, and macro re-entrant circuits that enable arrhythmogenic wave fronts. Unfortunately, the addition of lesion sets to address extra-pulmonic substrate does not always lead to higher success rates. (5) Thus, the five year arrhythmia-free survival in non-paroxysmal atrial fibrillation (NPAF) for a single endocardial catheter ablation procedure still remains low and has been reported at 28.4% with the efficacy after multiple procedures at 51.1%. (6) Surgical AF ablation also has evolved from the original open Cox Maze procedure, which never gained widespread acceptance due to its technical complexity and invasiveness, to a much more minimally invasive, video-assisted thoracoscopic approach with bipolar radiofrequency ablation (other energy modalities having come and gone) via clamping and pen with adequate results. (7)

However, there still remains difficulty in achieving durable transmural lesions by means of a thoracoscopic approach alone and recurrent atrial arrhythmias can often be seen, up to a 40% rate with one year follow up in an early paper on the subject. (8) Furthermore, confirmation of block and mapping of arrhythmias via an epicardial approach when working alone remains limited and difficult, possibly leading to suboptimal results. (9) This has led to the development of the hybrid AF ablation techniques utilizing both a surgical epicardial approach along with a transvenous endocardial approach, attempting to harness the benefits of each strategy while mitigating their shortcomings and hoping to achieve a synergistic benefit. (10) Currently the two most commonly used minimally invasive approaches in performing the epicardial ablation is either a thoracoscopic approach (10,11) or a pericardioscopic approach. (12)

Commonly, the surgical portion of the hybrid approach is prior to the transvenous portion in a staged approach, thereby, in principle, allowing the electrophysiologist to confirm epicardial linear lesions and pulmonary vein isolation (PVI); in addition to decreasing the burden of additional endocardial lesion sets needed to be applied by the electrophysiologist to achieve procedural end-points. While hybrid approaches have yielded improved outcomes at one year over either approach alone, success rates, particularly beyond one year, remain disappointingly low for such an invasive procedure. In fact, Pison et al. (10) reported on their experience with such a procedure, with a success rate of 83% at one year follow up without continuous monitoring with inclusion of PAF patients. Success rates for these procedures may be tempered by edema introduced during the surgical approach which limits electrophysiological mapping either simultaneously or shortly thereafter; thus, resulting in areas of extensive tissue edema masquerading as true transmural lesions. In addition, critical areas of arrhythmogenesis may be precluded from appropriate mapping and/or ablation. Krul et al. (13) describe a success rate of 75% at one year (no continuous monitoring was performed) in persistent AF using a real-time mapping approach that required customized equipment or a hybrid EP lab, which are not widely available.

We propose that the success rate of a hybrid atrial fibrillation ablation procedure can increase for both persistent AF (PeAF) and long-standing persistent AF (LSPeAF) by having the endocardial approach precede the surgical approach, which most centers should be able to perform. The endo-before -epi surgical hybrid AF ablation procedure is defined by a comprehensive endovascular approach preceding and guiding the epicardial ablation coupled with an extensive epicardial posterior wall ablation to replace the posterior "box lesion" and mitral isthmus lines and their resulting proarrhythmia.


Study Design and Population

The study was designed as a prospective observational study with 40 patients being enrolled between January 2012 and December 2014. The study was approved by the St. Vincent's Hospital Institutional Review Board and all patients gave informed consent. All patients had persistent or long-standing persistent AF, were highly symptomatic and had previously failed medical management with a class I or class III antiarrhythmic medication. Patients were chosen for the hybrid procedure if they were considered to be predisposed to a less efficacious outcome from a standard endocardial procedure based on one of the following criteria: (1) persistent AF with failure of antiarrhythmic drug therapy, (2) persistent AF with large left atrial size (> 90 mL) by CT scan or concomitant structural heart disease, (3) long-standing persistent AF, and (4) prior failed endocardial ablation. Refer to table 1 for patient characteristics. Patients greater than 18 years of age undergoing the hybrid AF procedure at St. Vincent's Medical Center Bridgeport, Connecticut were included in this study. Exclusion criteria included: pregnancy, incarceration, severe valvular disease or other cardiac indication for an open procedure and mechanical valves. Procedural complications were predefined as life-threatening or disabling complication or those requiring additional hospitalization for observation (stroke, systemic or pulmonary embolism, esophageal injury other than esophagitis, phrenic nerve injury, symptomatic pulmonary vein stenosis, pericardial effusion with or without tamponnade, groin complications, major bleeding) occurring within 30 days of the procedure.

Preoperative Care

For patients anticoagulated with warfarin, warfarin was discontinued five days before the endocardial procedure. Epicardial procedures were performed with INR of 1.7 or less. If the patient was taking a novel oral anticoagulation agent (NOAC), the NOAC was discontinued 12-48 hours prior and resumed the day after the epicardial procedure. High-risk patients, including those with prior cerebrovascular accident or hypercoagulable states, were bridged with enoxaparin prior to the procedure.

If not already prescribed, an antiarrhythmic drug (AAD) was initiated, amiodarone being the drug of choice if tolerated. After oral AAD load, an attempt at restoration of sinus rhythm was performed with one direct current cardioversion. If early recurrence of AF was noted, further attempts at restoration were deferred prior to the hybrid AF procedure. All patients underwent pre-procedural cardiac computer tomography evaluation to delineate the left atrium and pulmonary vein anatomy.

Endovascular Approach

The procedure is performed over two consecutive days. The endocardial approach was standardized and performed by a single operator. All patients receive a transesophageal echocardiogram to evaluate for intracardiac thrombus as well as other structural abnormalities for repair of which sternotomy would be required, at which time an open surgical Cox Maze procedure could be performed. General anesthesia is used throughout the endovascular approach with the esophageal temperature being monitored with a single sensor esophageal temperature probe placed under fluoroscopy. Venous access is performed at both the right and left femoral veins and once access is established, 3000 to 5000 units of heparin is administered. A duodecapolar catheter (St. Jude Medical, St Paul, MN) is placed along the lateral right atrial all and into the coronary sinus via the right femoral vein. A 10 Fr intravascular ultrasound catheter (St. Jude) is then placed in the right atrium to aid in performing transseptal puncture, guiding catheter location and monitoring for any cardiac complications. A 5.0 6.0 Fr quadripolar diagnostic catheter is advanced to the right ventricular apex for pacing and sensing. With a St Jude steerable sheath positioned at the interatrial septum, a single transseptal puncture is performed with the use of a Brockenbrough-1 needle under fluoroscopic and ultrasound guidance. Additional heparin is then administered with continual infusion and activated clotting time monitored with a goal of > 350 seconds via intraprocedural iStat (Abbot, Princeton, New Jersey) monitoring.

With the use of the St. Jude Velocity Ensite-Precision mapping system and a 20-pole circular catheter, an electro-anatomical map of the left atrium and pulmonary veins is created. If the patient presented in atrial fibrillation, complex fractional atrial electrograms are also mapped during the anatomical mapping of the left atrium.

Endovascular lesion sets are then applied with radiofrequency ablation with a St. Jude irrigated bidirectional ablation catheter. Wide area circumferential ablation with carinal lesions (if accessible) is performed around all pulmonary veins. A power cutoff of 30 watts and 15 watts is utilized along the anterior and posterior walls respectively. If a temperature rise in the esophagus greater than 0.2 degrees is seen, the radiofrequency ablation is discontinued in the area. A roof line is placed connecting the upper pulmonary veins along a posterior course as anatomically allowed. Integrity of the roof line is verified by changes in activation of the coronary sinus catheter compared to baseline and presence of split potentials along the line. Ablation of p re-procedural documented atrial tachycardias is then performed if deemed clinically relevant. Further lesions are then applied at the mapped complex fractionated electrogram (CFAE) sites. Confirmation of isolation of all pulmonary veins is then performed by demonstrating entrance and exit block with a St. Jude circular duodecapolar catheter. Adenosine and/or isoproterenol were not routinely used. If atrial fibrillation persists despite these lesion sets, typically no electrical cardioversion is performed to reduce the risk of post operative cerebrovascular accident while awaiting the epicardial approach.

Once isolation of all pulmonary veins and integrity of roof line has been confirmed, catheter and sheaths are withdrawn from the left atrium. Once within the right atrium, a cavo-tricuspid isthmus ablation line is performed regardless of whether or not atrial flutter has been previously observed. In addition, lesions are applied along the coronary sinus os. Once completed, heparin is then reversed with protamine and sheaths are removed from the femoral vein with manual compression utilized for hemostasis. Implantable loop recorders were then placed in all patients to allow for continuous cardiac monitoring after discharge.

Epicardial Approach

The epicardial approach is performed on day two also under general anesthesia. The electrophysiologist was present in the room to direct application of lesions based on available EnSite maps from the endocardial procedure. A double-lumen endotracheal tube is utilized for selective lung ventilation and a transesophageal echocardiography probe as well as an esophageal temperature probe is in place throughout the surgical approach. Surgery is started on the patient's right side after deflation of the right lung and with placement of three ports. Dissection is then performed to the pericardium with focus on localizing the phrenic nerve and esophagus. Rightsided ganglionated plexi (GP) are localized by burst pacing. If a "vagal response" is provoked, radiofrequency ablation is performed in this area. The right-sided pulmonary veins are then clamped utilizing the Atricure ablation clamp (Atricure, Mason, OH) and further dissection is performed posteriorly. An Atricure linear pen is utilized to ablate within the posterior left atrial wall as well as initiating the first-half of a roof line connecting the upper pulmonary veins. Focus is then turned to ablating areas that posed difficulties from an endovascular approach due to anatomy or safety. Further epicardial lesions are applied in areas of endovascularly-mapped CFAE regions as well as any clinically relevant sites of atrial tachycardia that were previously localized. After direct visualization of re-inflation of the right lung, ports are removed and access points are closed. Attention is then directed to the left side. Similarly, after deflation of the left lung, 3-4 ports are placed. Further dissection is then performed posteriorly. The ablation pen is further utilized to complete lesion sets to the posterior wall and finish the roof line as well as to complete lesions to further GPs and prior mapped sites that proved difficult via endovascular approach. The vein of Marshall is then localized and dissected from the left atrium. Ablation is performed within the ridge of the appendage. The posterior wall between the roof line and the mitral isthmus is completely ablated. Once ablations are completed, attention is turned to left atrial appendage closure using the AtriCure Atriclip.

Termination of atrial fibrillation is not a procedural endpoint and once the procedure is deemed complete, if atrial fibrillation persists, direct current cardioversion is applied to restore sinus rhythm. The left lung is then reinflated under direct visualization, ports removed and the left side closed. Mitral isthmus lines are not performed.

Post Operative Care

Oral anticoagulation is continued in all patients post conversion to sinus rhythm for at least 3 months. Thereafter, continuation of anticoagulation agent is determined by the patients' overall risk (CHADS-VASc score), (14,15) bleeding risk and patient preference.

Follow Up

After hospital discharge, the patients were monitored in office on a routine basis every three months for the first year and every four to six months thereafter for recurrence of atrial arrhythmia after ablation. Atrial arrhythmias occurring during the first three months, considered a blanking period, were not included. Oral antiarrhythmics were discontinued after this three-month blanking period. (16) Follow up with arrhythmia monitoring was continued for a minimum of 12 months.

End Points

The primary end-point was freedom from any atrial arrhythmia > 30 seconds, more than 91 days from the epicardial procedural date as defined in the guidelines at 12 month follow-up. (17)


Statistical analysis was completed using SPSS Statistics version 21.0 (IBM; Armonk, NY). Descriptive statistics include means and standard deviations for continuous variables and frequencies and percentages for categorical variables. A failure was defined according to Heart Rhythm Society Guidelines as any episode of AF, atrial flutter or atrial tachycardia (the latter two are considered identical for purpose of outcomes) lasting more than 30 seconds detected after the 3-month post-procedural blanking period by EKG or continuous implanted monitor. Outcomes were further compared between patients with LSPeAF versus PeAF using a Log-Rank comparison with statistical significance below a p-value of < 0.05.


Patient Characteristics

Forty patients underwent the procedure between June 2012 and December 2014. Thirty-one patients were classified as persistent (PeAF) while nine met criteria for long-standing persistent (LSPeAF). The median atrial fibrillation duration was 6.0 [+ or -] 4.5 years. The patients mean age was 61.7 [+ or -] 7.9 years with 70% being male. Baseline patient characteristics demonstrated in table 1.

The epicardial approach was able to be performed within 24 hours in 85% of patients. Left atrial appendage closure with the Atriclip was performed in 37/40 (92.5%). There were no procedural complications within 30 days and no patients required conversion to an open surgical procedure for completion of the procedure. Implantable cardiac monitoring (ICM) was in place (either with a newly placed ILR or prior implanted permanent pacemaker or defibrillator) in all patients at procedure completion. Oral antiarrhythmic agents were discontinued following an approximate three month blanking period after the procedure.


Follow up for 12 months was performed in all 40 patients.

At one year follow up all 40 patients with previously diagnosed persistent and long-standing persistent atrial fibrillation were documented to be in sinus rhythm. While atrial arrhythmias were seen, these were paroxysmal in nature. Freedom from recurrence of any atrial arrhythmia was seen in 35/40 patients (87.5%) outside the 3 month blanking window.

Freedom from recurrence of atrial arrhythmias trended higher in patients with documented persistent atrial fibrillation vs. long standing atrial fibrillation prior to the procedure, although this difference did not reach statistical significance. Despite this finding, maintenance of sinus rhythm on follow-up was documented in all patients (Table 3).


While endocardial catheter ablation has been well established in the management of paroxysmal atrial fibrillation, its success in persistent atrial fibrillation has been limited. This is likely due to a dynamic continuum of structural, electrical and contractile remodeling. (18) Better understanding of underlying pathophysiology has led to a better understanding of anatomical targets and advancements in technology have improved the available tools for performing minimally invasive procedures. We can now apply effective epicardial and endocardial lesions in a combined approach leading to the development of hybrid procedures incorporating epicardial lesion sets along with catheter-based endocardial approaches. Utilizing a hybrid approach to atrial fibrillation allows transmural, complete lesions and lesion sets can be completed in areas difficult to approach from an endocardial aspect alone when combining a minimally invasive epicardial approach with additional safety when applying lesions near the right phrenic nerve or esophagus.

In this report, we describe a novel approach to the hybrid AF ablation, utilizing a comprehensive endovascular approach preceding and guiding the epicardial ablation was created in response to the challenge of non-PAF and as a collaborative approach to optimize each approach's strengths and overcoming the logistic difficulties of real-time intraoperative mapping. The endovascular approach was often met with anatomic complexities or large areas of arrhythmic substrate that could not be addressed with an endovascular approach alone, therefore resulting in recurrent atrial arrhythmias after multiple such procedures. By using the electrophysiology study and ablation to guide, direct and tailor the epicardial approach, 87.5% of patients with either persistent or long-standing persistent AF were free of atrial arrhythmias at one year, as documented with continuous monitoring, and all documented events were noted to be paroxysmal in nature requiring no reintervention. This success rate validates the utility of a "reverse" hybrid approach (an endovascular guided epicardial approach) for the management of persistent and long-standing persistent atrial fibrillation.

Literature has shown that there can be multiple extra-pulmonic vein sources of initiation and maintenance of AF with the most common sites including the superior vena cava, ligament of Marshall, coronary sinus, crista terminalis, and left atrial posterior wall. (19, 20) The lesion set performed in this approach is systematic and certainly comprehensive which attributes to the high success rates.

The posterior left atrial wall is highly arrhythmogenic with a high concentration of fibrosis with heterogeneity of conduction properties with sites of fast-organized activity and high incidence of dominant frequencies. (18, 21) However, attempts at isolation of the posterior wall have proven difficult with either endocardial or epicardial alone since the gaps in the lines are arrhythmogenic. In an answer to this challenge, a multidisciplinary approach utilizing a pericardioscopic convergent procedure to epicardially segment the posterior left atrium has garnered improved success rates. (12, 22, 23) We utilized the improved pericardial access via a thoracoscopic approach to perform a comprehensive segmentation of the left atrial posterior wall along with other substrate modification. This allowed us to successfully isolate the pulmonary veins and silence the posterior left atrium, resulting in superior clinical results.

The autonomic ganglionated plexi (GP) have also been shown to likely contribute to the perpetuation of the AF substrate. GPs are anatomically located along the ligament of Marshall, the great vessels, at the right superior pulmonary vein (PV)-atrial junction, at the left superior PV-atrial junction, at the left inferior PV-atrial junction, and at the junction of the inferior vena cava. Direct stimulation of GPs trigger pulmonary vein ectopy and perpetuate atrial fibrillation by reduction of PV sleeve action potential duration, and shortening of the fibrillation cycle length. (24) Thus, we systematically performed GP mapping with ablation as this significantly increases success rates in patients with non-PAF. (25)

Another strength of the described procedure is that it addresses the often ignored arrhythmogenic regions in the non-PAF heart such as the ligament of Marshall (LOM), left atrial appendage (LAA) and coronary sinus with its inter-atrial musculature sleeves. The LOM contains parasympathetic and sympathetic nerve fibers along with Marshall bundles that insert into the LA free wall and CS forming connections and substrate for reentrant excitation. (26) In addition, the anatomical proximity of the LOM to the sympathetic nerves may provide a mechanism for adrenergic atrial tachyarrhythmia in humans. Thus, we directed our lesion set to the LOM by having the surgeon perform a LOM dissection; furthermore, LAA clipping likely modified the remaining LOM as well by mechanical disruption. The LAA is under-recognized and under-addressed as potential substrate for initiating and maintain atrial fibrillation, particularly with redo ablations as depicted by DiBiase et al. (27) This was suggested in our small database when we saw five patients terminate their AF with LAA clipping. We believe that the LAA clipping provides both a thromboembolic and an electrophysiologic benefit.

As to the coronary sinus, there is the clear presence of histoanatomic connections linking the inferior right atrium to the left atrial myocardium via a cuff of striated muscle around the coronary sinus in humans. (28) Overall, the presence of these variable muscular connections indicates a consistent pathway for interatrial propagation and possibly further reentrant flutters if not addressed. We feel we addressed this potential short fall by incorporating a CS os lesion set into the cavotricuspid isthmus line.

It was also noted that overall procedure time was able to be reduced with adoption of the herein described hybrid approach. This decrease in procedure time was noted in both the endocardial as well as the epicardial portions of the procedure.

The strengths of this study are that it represents a single-center study where the lesion-application strategy was uniform amongst all patients. It also shows an excellent one year arrhythmia-free survival even when accounting for the continuous monitoring strategy, the inclusion of very dilated left atria and the exclusion of patients with paroxysmal atrial fibrillation.


We describe promising results at 12 months in PeAF and LPeAF patients using a hybrid approach wherein the endovascular lesions are applied prior the epicardial compared to the traditional approach of epicardial lesions first compared to previously described reports and with higher success rates than in these same reports. All recurrent arrhythmias were paroxysmal in nature and required no intervention for management. Although clearly establishing the superiority of this approach would require a randomized trial, we believe it shows enough promise to warrant further investigation and longer-term data.


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Joseph J. Tiano, MD, is affiliated with St. Vincent's Medical Center, Bridgeport, Conneticut 06824; Robert Drennan, MD, is affiliated with Louisiana State University Health Sciences Center--New Orleans, 433 Bolivar St, New Orleans, Louisiana, 70112; John Novella, MD, is affiliated with St. Vincent's Medical Center, Bridgeport, Conneticut 06824; Rafael Squiteri, MD, is affiliated with St. Vincent's Medical Center, Bridgeport, Conneticut 06824; Malcolm Robinson, MD, is affiliated with St. Vincent's Medical Center, Bridgeport, Conneticut 06824; Albert DiMeo, MD, is affiliated with St. Vincent's Medical Center, Bridgeport, Conneticut 06824; Lindsey Scierka, MPH, is affiliated with Quinnipiac University, Hamden, Connecticut, 06511; Paul LeLorier, MD, is affiliated with Louisiana State University Health Sciences Center --New Orleans, 433 Bolivar St, New Orleans, Louisiana, 70112.
Table 1. Baseline Characterisitics

Baseline Characterisitics

Patient Characteristic   Percentage (%) or Mean [+ or -] SD

Gender                   Male = 70.0%
Age (Years)              61.7 [+ or -] 7.9
BMI (kg/[m.sup.2])       31.3 [+ or -] 6.8
AF Type                  Persistent = 77.5.0%
                         Long-standing persistent = 22.5%
AF Duration (Years)      6.0 [+ or -] 4.5
Mitral Regurgitation     Mild = 52.2%
                         Moderate = 42.5%
                         Severe ([dagger]) =5.0%
LVEF(%)                  55.7 [+ or -] 5.7
LA Size (cm)             4.7 [+ or -] 0.8
LA Volume (cc)           131.5 [+ or -] 46.9
Comorbidities            Diabetes = 17.5%
                         Hypertension = 80.0%
                         Obstructive sleep apnea = 55.0%
# of AADs Trialed        1.55 [+ or -] 0.7
Prior ablation           Yes = 22.5%

AAD: Antiarrhythmic drug
AF: Atrial fibrillation
BMI: Body Mass Index

LVEF: Left ventricular ejection fraction
LA: left atrium

([dagger]) : Refused open proceduret

Table 2. Follow Up Data

Data Point                      Value

Duration of Follow Up           12 Months = 100%
ILR or PPM/ICD Implanted        100.0%
Next Day Epicardial Approach    85%
LAA Clip Delivered              92.5%
Complications                   Intra-procedural complications =
                                Convert to Open = 0%
                                Post-op complications = 2.5%
                                  (1 patient)

ICD: Internal cardiac defibrillator

ILR: Implantable loop recorder

LAA: Left atrial appendage

PPM: Pacemaker

Table 3. Post Procedural Data

Data Point                       Value

AT/AF Recurrence                 12.5%
Average Time to AAD              3.28 [+ or -] 2.0
Discontinuation (Months)
Sustained Atrial Arrhythmia      25.0%
within Blanking Window
Patients Required DCCV           5.0%
Patients Requiring Redo          0.0%

AAD: Antiarrhythmic drug

AF: Atrial fibrillation

AT: Organized atrial rhythm

DCCV: DC cardioversion

Table 3. Recurrence Details

                               Arrhythmia during   Time to
Patient   AF Type   Prior EP   blanking period     Recurrence (days)

2         LSPeAF    Yes        Yes                 319
6         LSPeAF    Yes        No                  341
8         PeAF      Yes        Yes                 303
35        LSPeAF    No         No                  234
38        PeAF      No         Yes                 108

          Recurrence          Repeat ablation
Patient   Rhythm       DCCV   required

2         AT           Yes    No
6         AT           Yes    No
8         AT           No     No
35        AF           No     No
38        AT           No     No

AF: Atrial fibrillation

AT: Organized atrial rhythm

DCCV: Cardioversion required

LSPeAF: Long-standing persistent atrial fibrillation

PeAF: Persistent atrial fibrillation
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Author:Tiano, Joseph J.; Drennan, Robert; Novella, John; Squiteri, Rafael; Robinson, Malcolm; DiMeo, Albert
Publication:The Journal of the Louisiana State Medical Society
Article Type:Report
Date:May 1, 2017
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