David O. Martin

Inflammation as a Risk Factor for Atrial Fibrillation

Background—The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort. Methods and Results—CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9±1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P =0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P =0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P <0.001). Conclusions—CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.

Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications.

Background—The objective of this study was to assess the impact of intracardiac echocardiography (ICE) on the long-term success and complications in patients undergoing pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Methods and Results—Three hundred fifteen patients underwent PVI for treatment of AF. Each patient underwent ostial isolation of all PVs using a cooled-tip ablation catheter. PVI was performed using circular mapping (CM) alone (group 1, 56 patients), CM and ICE (group 2, 107 patients), and CM and ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (group 3, 152 patients). After a mean follow-up time of 417±145 days, 19.6% (11 of 56), 16.8% (18 of 107), and 9.8% (15 of 152) of patients in groups 1, 2, and 3 experienced recurrence of AF, respectively. Moreover, whereas no group 3 patient experienced severe (>70%) PV stenosis, severe PV stenosis was documented in 3 (3.5%) of 56 patients in group 1 and in 2 (1.8%) of 107 patients in group 2 (P <0.05). No embolic events were detected in group 3 patients. Conclusions—Intracardiac echocardiography improves the outcome of cooled-tip PVI. Power adjustment guided by direct visualization of microbubble formation reduces the risk of PV stenosis and improves long-term cure.

Pulmonary-Vein Isolation for Atrial Fibrillation in Patients with Heart Failure

BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure. METHODS In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation. RESULTS In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another. CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

Pulmonary Vein Stenosis After Radiofrequency Ablation of Atrial Fibrillation Functional Characterization, Evolution, and Influence of the Ablation Strategy

Background—Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described. Methods and Results—PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (≥70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P =0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans. Conclusions—V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.

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.

Ablation for longstanding permanent atrial fibrillation: Results from a randomized study comparing three different strategies

BACKGROUND This prospective multicenter randomized study aimed to compare the efficacy of 3 common ablation methods used for longstanding permanent atrial fibrillation (AF). METHODS A total of 144 patients with longstanding permanent AF (median duration 28 months) were randomly assigned to circumferential pulmonary vein ablation (CPVA, group 1, n = 47), to pulmonary vein antrum isolation (PVAI, group 2, n = 48) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms (CFAE) in both atria followed by a pulmonary vein antrum isolation (CFAE + PVAI, group 3, n = 49). RESULTS Scarring in the left atrium and structural heart disease/hypertension were present in most patients (65%). After a mean follow-up of 16 months, 11% of patients in group 1, 40% of patients in group 2 and 61% of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs (P < .001). Sinus rhythm maintenance would increase respectively to 28% (group 1), 83% (group 2), and 94% (group 3) after 2 procedures and with antiarrhythmic drugs (AADs, P < .001). The AF terminated during ablation, either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia, in 13% of patients (group 1), 44% (group 2), and 74% (group 3) respectively. CFAE alone, performed as the first step of the ablation in group 3, organized AF in only 1 patient. CONCLUSION In this study, the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longstanding permanent AF. Electrical isolation of the PVs, although inadequate if performed alone, is relevant to achieve long-term sinus rhythm maintenance after ablation. Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation.

Atrial Fibrillation Ablation in Patients With Therapeutic International Normalized Ratio : Comparison of Strategies of Anticoagulation Management in the Periprocedural Period

Background— The best approach to management of anticoagulation before and after atrial fibrillation ablation is not known. Methods and Results— We compared outcomes in consecutive patients undergoing pulmonary vein antrum isolation for persistent atrial fibrillation. Early in our practice, warfarin was stopped 3 days before ablation, and a transesophageal echocardiogram was performed to rule out clot. Enoxaparin, initially 1 mg/kg twice daily (group 1) and then 0.5 mg/kg twice daily (group 2), was used to “bridge” patients after ablation. Subsequently, warfarin was continued to maintain the international normalized ratio between 2 and 3.5 (group 3). Minor bleeding was defined as hematoma that did not require intervention. Major bleeding was defined as either cardiac tamponade, hematoma that required intervention, or bleeding that required blood transfusion. Pulmonary vein ablation was performed in 355 patients (group 1=105, group 2=100, and group 3=150). More patients had spontaneous echocardiographic contrast in groups 1 and 2. One patient in group 1 had an ischemic stroke compared with 2 patients in group 2 and no patients in group 3. In group 1, 23 patients had minor bleeding, 9 had major bleeding, and 1 had pericardial effusion but no tamponade. In group 2, 19 patients had minor bleeding, and 2 patients developed symptomatic pericardial effusion with need for pericardiocentesis 1 week after discharge. In group 3, 8 patients developed minor bleeding, and 1 patient developed pericardial effusion with no tamponade. Conclusions— Continuation of warfarin throughout pulmonary vein ablation without administration of enoxaparin is safe and efficacious. This strategy can be an alternative to bridging with enoxaparin or heparin in the periprocedural period.

Pulmonary Vein Stenosis after Catheter Ablation of Atrial Fibrillation: Emergence of a New Clinical Syndrome

Context Because electrical signals initiating atrial fibrillation originate in the pulmonary veins, radiofrequency catheter ablation has been highly successful in curing the arrhythmia. Pulmonary vein stenosis is a recognized complication of this procedure, but past research has not established its frequency or clinical characteristics. Contribution Of 335 patients who received catheter ablation, 18 developed severe pulmonary vein stenosis. Only 44% were symptomatic. Failure to recognize the problem often led to inappropriate work-up and treatment. After pulmonary vein dilatation and stenting, 57% of patients improved. Implications Pulmonary vein stenosis following catheter ablation of atrial fibrillation is relatively common and clinically recognizable. Mechanical relief of venous obstruction can alleviate symptoms. The Editors Atrial fibrillation is one of the most common cardiac rhythm disorders and is associated with significant morbidity and mortality. Recent advances in the pathophysiologic understanding of this disorder have pointed to a focal origin that is mainly localized in the pulmonary veins and is thus amenable to ablative catheter procedures (1-6). Pulmonary vein stenosis is a recognized potential complication of radiofrequency ablation. Its incidence has been reported to range from 3% to 42%, depending on the ablative technique used and the method of assessment (6-11). Recognition of pulmonary vein stenosis is important to avoid unnecessary work-up and to allow initiation of appropriate treatment. However, reports on the constellation of signs and symptoms characterizing pulmonary vein stenosis are lacking. In this study, we describe our experience with patients who developed pulmonary vein stenosis as a complication of radiofrequency ablation of atrial fibrillation. Methods Study Sample Three hundred thirty-five patients (272 men; mean age, 54.0 years [range, 18 to 79 years]) with symptomatic, drug-refractory atrial fibrillation (mean duration [SD], 5.4 3.6 years) were referred to our laboratory for electrophysiologic study and catheter ablation. Therapy with antiarrhythmic drugs and use of oral anticoagulants were discontinued 5 half-lives and 5 days, respectively, before ablation. In all but three patients, amiodarone was withdrawn 1 month before the procedure. Informed consent was obtained from all patients before the procedure, and the institutional review board approved the collection and analysis of the data. In 71 patients, we used a three-dimensional nonfluoroscopic electroanatomic system (CARTO, Biosense Webster, Diamond Bar, California) to map and ablate arrhythmogenic pulmonary veins, as described elsewhere (3). Briefly, this system uses a low-level magnetic field to continuously record the mapping catheter location and create a catalog of electrical activity. The acquired information is then color-coded and displayed on a three-dimensional chamber geometry model of the heart chamber of interest. In 264 additional patients, we instead performed circumferential mapping and electrical isolation of all pulmonary veins, regardless of demonstration of ectopic activity. Procedure Description Patients came to the electrophysiology laboratory while fasting. Immediately before the procedure, transesophageal echocardiography was performed in all patients to exclude left atrial thrombus. A custom-made catheter (Cardiac Assist Device, Inc., Cleveland, Ohio) was placed in the coronary sinus. The proximal eight electrodes were positioned between the superior vena cava and the high crista terminalis, whereas the distal eight electrodes were placed in the coronary sinus. A transesophageal recording lead was used to record activation of the left atrial posterior wall. Mapping of left atrium and pulmonary veins was completed after the left atrium was accessed through the transseptal approach. A circular catheter (LASSO, Biosense Webster) and a steerable quadripolar catheter were placed in the pulmonary veins for mapping and ablation, respectively, through separate transseptal access points. Quadripolar 4-mmtip, 8-mmtip (Biosense Webster), and cooled-tip (Chilli, EPT, Sunnyvale, California) catheters were used for ablation. The procedure end point was the demonstration of electrical isolation of all pulmonary veins from the left atrium by evidence of entrance block. Initially, radiofrequency lesions were delivered inside the veins. For most patients, however, proximal isolation was obtained by energy delivery at the pulmonary veinleft atrium junction, which was defined by a phase-array intracardiac echocardiographic probe or by pulmonary vein angiography. The latter was performed during adenosine-induced asystole for better resolution. In patients in whom the electroanatomic system was used, only the superior pulmonary veins were targeted, unless firing from other veins was noted. The pulmonary vein profiles were reconstructed by using the electroanatomic system and by angiography. The procedure end point was pulmonary vein isolation, elimination of ectopic activity capable of initiating atrial fibrillation, or both. Follow-up Patients were given aspirin immediately after the procedure, and warfarin was restarted on the same evening. Antiarrhythmic medications were used for 6 weeks in patients who had permanent atrial fibrillation before the procedure. An arrhythmia transmitter was given to all patients before hospital discharge for detection of recurrent atrial fibrillation. Routine follow-up visits took place 3, 6, and 12 months after the procedure. Spiral computed tomography (CT) of the pulmonary veins, with three-dimensional reconstruction, was performed 3 months after ablation in all patients, regardless of the development of symptoms, to screen for pulmonary vein stenosis. Computed tomography was considered earlier if symptoms suggestive of stenosis developed; it was repeated at 6 and 12 months if any degree of pulmonary vein narrowing was observed. Pulmonary vein stenosis was judged by digital measurements of luminal diameters on adjacent segments as well as by comparison with previous films, when available. Stenosis was considered mild if luminal narrowing was less than 50%, moderate if luminal narrowing was 50% to 70%, or severe if luminal narrowing was more than 70%. Statistical Analysis We used the paired t-test to compare perfusion scan data and the Fisher exact test to evaluate the relation between the number of stenosed pulmonary veins and symptoms. StatXact software, version 3.0 (Cytel Corp., Cambridge, Massachusetts), was used for these analyses. Results Demographic characteristics of the study sample are presented in Table 1. At the 6-month follow-up visit, pulmonary vein isolation guided by the circular mapping technique had cured atrial fibrillation without use of medications in 80% of patients (212 of 264). Thirty-five patients underwent a second procedure, which resulted in an overall success rate of 92% (243 of 264 patients). This represented a significant improvement when compared with the electroanatomically guided technique, in which only 30% patients (21 of 71) were free of arrhythmia while not taking medications. Table 1. Demographic Characteristics of the Study Sample at Baseline Eighteen of 335 patients (5% [95% CI, 3% to 8%]) developed severe pulmonary vein stenosis, detected by spiral CT, a mean (SD) of 5.2 2.6 months after ablation. The mean age of these patients was 50.6 years (range, 26 to 71 years), and 78% were men. Five of these 18 patients (28%) had structural heart disease. The mean number of pulmonary veins ablated was three per patient (range, two to four per patient). Twelve patients had ablation guided by the circular mapping technique, and 6 patients had ablation guided by the CARTO system. Shortness of breath, the only respiratory symptom detected before the ablation procedure, was present in 5 patients and was attributed to atrial fibrillation. One patient had underlying pulmonary disease (asthma). Eight patients with severe pulmonary vein stenosis (44%) were asymptomatic. Among patients who had symptoms, shortness of breath was the most prevalent (8 patients [44%]), followed by cough (7 patients [39%]) and hemoptysis (5 patients [28%]). Pleuritic pain was observed in 4 patients (22%) and was usually associated with hemoptysis and cough. The presence of severe stenosis in more than one pulmonary vein was associated with a higher risk for symptoms (relative risk, 12.5 [CI, 1.2 to 391]; P = 0.04). Radiographic findings were abnormal in 9 of the 18 patients with severe stenosis (50%). The most common abnormal finding was lung consolidation (observed in 78% of patients), followed by left pleural effusions (observed in 56% of patients). Of note, in 7 of the 9 patients with radiologic abnormalities of the lungs (78%), symptoms were initially attributed to other diseases: pneumonia (4 patients), lung cancer (1 patient), and pulmonary embolism (2 patients). It is important to note that pulmonary vein stenosis was not initially considered in any of the patients who had the disorder. Misdiagnoses led to improper diagnostic and therapeutic procedures, such as prolonged antibiotic treatment (5 patients), treatment for possible asthmatic syndrome and bronchitis (3 patients), placement of a vena cava filter (1 patient), and lung resection surgery (1 patient). Table 2 summarizes the clinical and radiologic findings and pulmonary vein interventions performed. Of interest, in 5 patients who initially presented with symptomatic pulmonary vein stenosis (50%), symptoms spontaneously resolved before interventional procedures were undertaken. Table 2. Summary of Clinical and Radiologic Findings and Pulmonary Vein Interventions in 18 Patients Lung perfusion scans were obtained before and after pulmonary vein dilatation and showed a significant improvement in perfusion after the intervention. Average pulmonary flow to the affected lung increased from 15% (CI, 2% to 33%) to 23% (

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.

Relationship between successful ablation sites and the scar border zone defined by substrate mapping for ventricular tachycardia post-myocardial infarction

Introduction: It is unknown if identification of scar border zones by electroanatomical mapping correlates with successful ablation sites determined from mapping during ventricular tachycardia (VT) post‐myocardial infarction (MI). We sought to assess the relationship between successful ablation sites of hemodynamically stable post‐MI VTs determined by mapping during VT with the scar border zone defined in sinus rhythm.