J. David Burkhardt

Feasibility and Safety of Dabigatran Versus Warfarin for Periprocedural Anticoagulation in Patients Undergoing Radiofrequency Ablation for Atrial Fibrillation Results From a Multicenter Prospective Registry

OBJECTIVES The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation (AF) ablation. BACKGROUND AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications. The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown. METHODS We performed a multicenter, observational study from a prospective registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States. All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran, with the dose held on the morning of the procedure, were matched by age, sex, and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period. RESULTS A total of 290 patients, including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin, were included in the study. The mean age was 60 years with 79% being male and 57% having paroxysmal AF. Both groups had a similar CHADS(2) score, left atrial size, and left ventricular ejection fraction. Three thromboembolic complications (2.1%) occurred in the dabigatran group compared with none in the warfarin group (p = 0.25). The dabigatran group had a significantly higher major bleeding rate (6% vs. 1%; p = 0.019), total bleeding rate (14% vs. 6%; p = 0.031), and composite of bleeding and thromboembolic complications (16% vs. 6%; p = 0.009) compared with the warfarin group. Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications (odds ratio: 2.76, 95% confidence interval: 1.22 to 6.25; p = 0.01) on multivariate regression analysis. CONCLUSIONS In patients undergoing AF ablation, periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy.

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Background—The role of pulmonary vein (PV) isolation in ablative treatment of atrial fibrillation (AF) has been debated in conflicting reports. We sought to compare PV conduction in patients who had no AF recurrence (group I), patients who could maintain sinus rhythm on antiarrhythmic medication (group II), and patients who had recurrent AF despite antiarrhythmic medication (group III) after PV antrum isolation (PVAI). Methods and Results—PV conduction was examined in consecutive patients undergoing second PVAI for AF recurrence. We also recruited some patients cured of AF to undergo a repeat, limited electrophysiological study at >3 months after PVAI. All patients underwent PVAI with an intracardiac echocardiography (ICE)–guided approach with complete isolation of all 4 PV antra (PVA). The number of PVs with recurrent conduction and the shortest atrial to PV (A-PV) conduction delay was measured with the use of consistent Lasso positions defined by ICE. Late AF recurrence was defined as AF >2 months after PVAI with the patient off medications. Patients in groups I (n=26), II (n=37), and III (n=44) did not differ at baseline (38% permanent AF; ejection fraction 53±6%). Recurrence of PV–left atrial (LA) conduction was seen in 1.7±0.8 and 2.2±0.8 PVAs for groups II and III but only in 0.2±0.4 for group I (P=0.02). In patients with recurrent PV-LA conduction, the A-PV delay increased from the first to second procedure by 69±47% for group III, 267±110% for group II, and 473±71% for group I (P<0.001). When pacing was at a faster rate, A-PV block developed in all 5 of the group I patients with recurrent PV-LA conduction. Conclusions—The majority of patients with drug-free cure show no PV-LA conduction recurrence. Substantial A-PV delay is seen in patients able to maintain sinus rhythm on antiarrhythmic medication or cured of AF compared with patients who fail PVAI.

Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation?: results from a multicenter study.

OBJECTIVES This study investigated the left atrial appendage (LAA) by computed tomography (CT) and magnetic resonance imaging (MRI) to categorize different LAA morphologies and to correlate the morphology with the history of stroke/transient ischemic attack (TIA). BACKGROUND LAA represents one of the major sources of cardiac thrombus formation responsible for TIA/stroke in patients with atrial fibrillation (AF). METHODS We studied 932 patients with drug-refractory AF who were planning to undergo catheter ablation. All patients underwent cardiac CT or MRI of the LAA and were screened for history of TIA/stroke. Four different morphologies were used to categorize LAA: Cactus, Chicken Wing, Windsock, and Cauliflower. RESULTS CT scans of 499 patients and MRI scans of 433 patients were analyzed (age 59 ± 10 years, 79% were male, and 14% had CHADS(2) [Congestive heart failure, hypertension, Age >75, Diabetes mellitus, and prior stroke or transient ischemic attack] score ≥2). The distribution of different LAA morphologies was Cactus (278 [30%]), Chicken Wing (451 [48%]), Windsock (179 [19%]), and Cauliflower (24 [3%]). Of the 932 patients, 78 (8%) had a history of ischemic stroke or TIA. The prevalence of pre-procedure stroke/TIA in Cactus, Chicken Wing, Windsock, and Cauliflower morphologies was 12%, 4%, 10%, and 18%, respectively (p = 0.003). After controlling for CHADS2 score, gender, and AF types in a multivariable logistic model, Chicken Wing morphology was found to be 79% less likely to have a stroke/TIA history (odd ratio: 0.21, 95% confidence interval: 0.05 to 0.91, p = 0.036). In a separate multivariate model, we entered Chicken Wing as the reference group and assessed the likelihood of stroke in other groups in relation to reference. Compared with chicken wing, cactus was 4.08 times (p = 0.046), Windsock was 4.5 times (p = 0.038), and Cauliflower was 8.0 times (p = 0.056) more likely to have had a stroke/TIA. CONCLUSIONS Patients with Chicken Wing LAA morphology are less likely to have an embolic event even after controlling for comorbidities and CHADS2 score. If confirmed, these results could have a relevant impact on the anticoagulation management of patients with a low-intermediate risk for stroke/TIA.

Left Atrial Appendage An Underrecognized Trigger Site of Atrial Fibrillation

Background— Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation. Methods and Results— Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12±3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (P<0.001). Conclusions— The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.

Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation The Impact of Periprocedural Therapeutic International Normalized Ratio

Background— Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication. Methods and Results— We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively; P>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%]; P>0.05), were equally distributed. Conclusion— The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.

Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Atrial fibrillation ablation using a robotic catheter remote control system: initial human experience and long-term follow-up results.

OBJECTIVES We present the initial clinical human experience with the use of a robotic remote navigation system (Hansen Medical, Mountain View, California), to perform left and right atrial mapping and radiofrequency ablation of atrial fibrillation (AF) and atrial flutter (AFL). BACKGROUND Catheter ablation is an established curative modality for various arrhythmias. A robotic steerable sheath system (SSS) (Hansen Medical) allows better catheter stability and greater degrees of freedom of catheter movement. METHODS A total of 40 patients (mean age 57 years) with antiarrhythmic drug (AAD)-refractory AF (23 had also concomitant documented typical AFL) were studied. Three-dimensional reconstruction of the corresponding atrial chamber anatomy was performed with the CARTO electroanatomic mapping system (Biosense Webster, Diamond Bar, California or the EnSite NavX system (St. Jude Medical, Minneapolis, Minnesota) in combination with the Artisan catheter (Hansen Medical). In patients undergoing AF ablation, 2 transseptal punctures were performed under intracardiac ultrasound (ICE) guidance, with one of the punctures being performed using SSS. Pulmonary vein antrum isolation was performed with a 3.5-mm thermocool catheter manipulated with the use of the SSS and was verified by circular mapping. Patients were followed clinically for recurrence of arrhythmia with an event transmitter and ambulatory holter monitoring. Clinical recurrence of AF/AFL was defined as AF/AFL episodes >1 min in duration. RESULTS Pulmonary vein antrum isolation was performed in 40 patients, including 23 with concomitant typical AFL ablation. All pulmonary veins, including the superior vena cava, were successfully isolated. In 23 of 40 patients, cavotricuspid ablation was also performed with bidirectional block obtained. At 1-year follow-up, 34 patients (86%) and 5 patients were free from atrial arrhythmia off AADs and on AADs, respectively. CONCLUSIONS This preliminary human experience suggests that mapping and ablation of AFL and AF using this novel robotic catheter with remote control system is feasible with similar results to conventional approach.

Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: Results from a multicenter study

BACKGROUND/OBJECTIVE The purpose of this prospective multicenter study was to compare results of catheter ablation in patients with paroxysmal atrial fibrillation (PAF) and those with nonparoxysmal atrial fibrillation (NPAF). The impact and the role of repeat catheter ablation were assessed in patients with recurrence. METHODS/RESULTS One thousand four hundred four patients underwent catheter ablation for atrial fibrillation (AF) performed by 12 operators at four institutions using a single technique guided by intracardiac echocardiography. Of these patients, 728 had PAF and 676 had NPAF. Among the NPAF patients, 293 had persistent AF and 383 had long-standing persistent AF. Patients with NPAF had a higher incidence of hypertension and/or structural heart disease (64.8% vs 48.5%, P = .003) and a lower mean left ventricular ejection fraction (53.3% +/- 8.7% vs 55.7 +/- 6.5%, P <.001). All patients underwent antral isolation of all four pulmonary veins and the superior vena cava. At mean follow-up of 57 +/- 17 months, 565 of 728 patients with PAF and 454 of 676 patients with NPAF (77.6% vs 67.2%, P <.001) had freedom from AF after a single ablation procedure. For arrhythmia recurrences, 74.2% (121/163) patients with PAF and 74.8% (166/222) with NPAF underwent repeat ablation, after which 92.4% patients with PAF and 84.0% patients with NPAF remained free from AF. CONCLUSION Pulmonary vein antrum isolation guided by intracardiac echocardiography results in significant freedom from AF, even when performed by multiple operators in different centers. At least moderate efficacy can be achieved in patients with NPAF, although the success rate is lower than in patients with PAF. Considerably higher success can be achieved in both groups with repeat ablation.

Brief Communication: Atrial–Esophageal Fistulas after Radiofrequency Ablation

Context Cardiologists sometimes use catheter radiofrequency ablation procedures near the posterior wall of the left atrium to cure atrial fibrillation. Contribution This retrospective case series describes 9 patients with atrialesophageal fistulas following catheter ablation for atrial fibrillation. They presented 10 to 16 days after the procedure with nonspecific findings, such as fever, leukocytosis, and neurologic abnormalities. All died. Only 4 received correct diagnoses before death. Cautions Case reports cannot establish how often ablation-related atrialesophageal fistulas occur. Implications Atrialesophageal fistulas that occur after ablation procedures involving the left atrium may have an indolent yet ultimately catastrophic presentation. The Editors Catheter ablation around the pulmonary vein region of the posterior left atrium is increasingly used to cure atrial fibrillation. Generally, the procedure is safe and effective (1), but the posterior wall of the left atrium is adjacent to the esophagus (Figure) and radiofrequency ablation procedures may substantially elevate the temperature within the esophageal lumen (2). Atrialesophageal fistulas may result from this thermal injury and subsequent necrosis. We searched English-language and nonEnglish-language literature through January 2006 using MEDLINE and found 3 reported cases of this complication following percutaneous atrial fibrillation ablation (3, 4). In this report, we describe an additional 9 patients who developed atrialesophageal fistulas after catheter ablation for atrial fibrillation. Figure. Three-dimensional computed tomographic reconstruction of the left atrium in relation to the esophagus. Methods Although devastating complications of procedures are infrequently systematically reported, physicians performing these procedures sometimes discuss them informally. Thus, we used an anonymous volunteer reporting method to identify cases that occurred between January 2004 and December 2005. We contacted physicians at several institutions who had treated patients with this complication and asked them to provide us with relevant medical records without identifying features. We then reviewed the medical records and entered demographic, clinical presentation, treatment, and survival data into the Cleveland Clinic Atrial Fibrillation Database. All physicians agreed to publication of general case information provided that the identity of the patients, themselves, and their institutions remained anonymous. Studies using the Atrial Fibrillation Database have been approved by the Cleveland Clinic Institutional Review Board. No funding was received to support this study. Results Physicians reported 9 patients with atrialesophageal fistula formation after ablation procedures (Table 1). The patients were treated at centers and by physicians with a wide range of case volumes and experience (Table 2). Seven patients presented to their primary care physician, emergency department, or cardiologist before hospitalization with nonspecific symptoms. Presentations occurred within about 2 weeks of the ablation procedures (mean, 12 days [range, 10 to 16 days]). Table 1. Characteristics of Patients Table 2. Atrial Fibrillation Ablations Performed Annually at Each of the Centers Reporting a Case of Atrial-Esophageal Fistula Patients presented with general malaise, leukocytosis, and persistent fever of undetermined origin. One patient who was admitted with persistent bacteremia had blood cultures that showed multiple bacterial species, including -streptococcus, micrococcus, and Candida albicans. All patients developed septic shock and cardiovascular collapse. Eight patients had neurologic findings consistent with multiple embolic strokes. Of these, 2 had intravascular air on computed tomography. Six patients had transesophageal echocardiography that yielded findings consistent with endocarditis. One of the echocardiograms showed evidence of vegetation or possible food particulate originating from the posterior wall of the left atrium. Two patients presented with symptoms consistent with transient angina associated with ST-segment elevation on electrocardiography. Three patients reported substantial gastrointestinal bleeding, but 5 patients had occult bleeding documented by fecal testing. All 9 patients died. Four patients received diagnoses of atrialesophageal fistula before death. Only 4 patients had computed tomography, which identified the atrialesophageal fistula in 3 patients. The remaining fistulas were diagnosed at autopsy. Of the 4 patients who received correct diagnoses before death, 3 had surgery and 1 died before surgery could be performed. All patients underwent autopsy, which confirmed or provided the diagnosis of atrialesophageal fistula. Discussion Esophageal damage, perforation, and atrialesophageal fistulas were first described after posterior left atrial radiofrequency ablation performed during open-heart surgery. Atrialesophageal fistulas were diagnosed during postoperative days 5 to 7 (5). Patients presented with neurologic deficits from air emboli, massive gastrointestinal bleeding, and septic shock (6). The first descriptions in the medical literature of atrialesophageal fistula formation after percutaneous radiofrequency catheter ablation, including 3 cases from experienced centers, were published in 2004 (3, 4). The patients in the published cases presented with signs and symptoms similar to those reported in this case series. All patients presented with nonspecific signs and symptoms, such as dysphagia, odynophagia, intermittent cardiac or neurologic ischemia (air emboli, vegetation, or both), persistent fever, bacteremia, fungemia, and melena. All patients presented to their physicians, often several times, with this constellation of symptoms in the weeks after their ablation procedure. Esophageal damage resulting from the previous ablation procedure was not considered in the differential diagnosis. Although atrialesophageal fistula formation is apparently rare, it seems to almost always be fatal. Therefore, evaluation and management of patients presenting with this potential complication must focus on rapid diagnosis and triage. Fever, malaise, leukocytosis, dysphagia, and neurologic symptoms in patients with a recent catheter ablation procedure should raise suspicion of atrialesophageal fistula. Computed tomography of the chest or head may reveal intravascular air. Air localized to the intravascular space may arise from a communication between the gastrointestinal tract and the vasculature, and atrialesophageal fistula must be considered. Of note, endoscopy with insufflation of the esophagus should be avoided to prevent further air embolism. Although all 9 patients in our series died, a previously published report documented survival after rapid surgical correction (4). Therefore, survival may depend on rapid diagnosis and prompt surgical intervention. Retrospective case series based on anonymous identification of cases and retrospective medical record review have several limitations. Although anonymous identification of cases facilitates the reporting of data on poor outcomes, lack of systematic monitoring across many physicians and procedures prevents assessment of the incidence of complications. Some relevant clinical information may not have been recorded in medical records, and patients did not receive uniform follow-up and work-up for complications after their ablation procedures. In conclusion, left atrialesophageal fistula formation is a rare but frequently fatal complication of radiofrequency catheter ablation for atrial fibrillation. Physicians must have a high index of suspicion for this complication in patients recently undergoing catheter ablation and presenting with the constellation of symptoms described in this report. Awareness of this potential complication is particularly important for primary care physicians and emergency department physicians, because rapid diagnosis and appropriate triage of affected patients may be crucial to survival. Early surgical intervention seems to be the best opportunity to improve survival. Further research is needed to determine effective strategies to avoid esophageal injury during catheter ablation procedures.

Assessment of temperature, proximity, and course of the esophagus during radiofrequency ablation within the left atrium

Background—Left atrioesophageal fistula is a devastating complication of atrial fibrillation ablation. There is no standard approach for avoiding this complication, which is caused by thermal injury during ablation. The objectives of this study were to evaluate the course of the esophagus and the temperature within the esophagus during pulmonary vein antrum isolation (PVAI) and correlate these data with esophagus tissue damage. Methods and Results—Eight-one patients presenting for PVAI underwent esophagus evaluation that included temperature probe placement. Esophagus course was obtained with computed tomography, 3D imaging (NAVX), or intracardiac echocardiography. For each lesion, the power, catheter and esophagus temperature, location, and presence of microbubbles were recorded. Lesion location and esophagus course were defined with 6 predetermined left atrial anatomic segments. Endoscopy evaluated tissue changes during and after PVAI. Of 81 patients, the esophagus coursed near the right pulmonary veins in 23 (28.4%), left pulmonary veins in 31 (38.3%), and mid-posterior wall in 27 (33%). Esophagus temperature was significantly higher during left atrial lesions along its course than with lesions elsewhere (38.9±1.4°C, 36.8±0.5°C, P<0.01). Lesions that generated microbubbles had higher esophagus temperatures than those without (39.3±1.5°C, 38.5±0.9°C, P<0.01). Power was not predictive of esophagus temperatures. Distance between the esophagus and left atrium was 4.4±1.2 mm. Conclusions—Lesions near the course of the esophagus that generated microbubbles significantly increased esophagus temperature compared with lesions that did not. Power did not correlate with esophagus temperatures. Esophagus variability makes the avoidance of lesions along its course difficult. Rather than avoiding posterior lesions, emphasis could be placed on better esophagus monitoring for creation of safer lesions.