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Background Atrioventricular (AV)-synchronous single-chamber leadless pacing using a mechanical atrial sensing algorithm produced high AV synchrony in clinical trials, but clinical practice experience with these devices has not yet been described. Objective To describe pacing outcomes and programming changes with AV-synchronous leadless pacemakers in clinical practice. Methods Consecutive patients without persistent atrial fibrillation who received an AV-synchronous leadless pacemaker and completed follow-up between February 2020 and April 2021 were included. We evaluated tracking index (atrial mechanical sense followed by ventricular pace [AM-VP] divided by total VP), total AV synchrony (sum of AM-ventricular sense [AM-VS], AM-VP, and AV conduction mode switch), use of programming optimization, and improvement in AV synchrony after optimization. Results Fifty patients met the inclusion criteria. Mean age was 69 ± 16.8 years, 24 (48%) were women, 24 (48%) had complete heart block, and 17 (34%) required ≥50% pacing. Mean tracking index was 41% ± 34%. Thirty-five patients (70%) received ≥1 programming change. In 36 patients with 2 follow-up visits, tracking improved by +9% ± 28% (P value for improvement = .09) and +18% ± 19% (P = .02) among 15 patients with complete heart block. Average total AV synchrony increased from 89% [67%, 99%] to 93% [78%, 100%] in all patients (P = .22), from 86% [52%, 98%] to 97% [82%, 99%] in those with complete heart block (P = .04), and from 73% [52%, 80%] to 78% [70%, 85%] in those with ≥50% pacing (P = .09). Conclusion In patients with AV-synchronous leadless pacemakers, programming changes are frequent and are associated with increased atrial tracking and increased AV synchrony in patients with complete heart block., Graphical abstract

BACKGROUND: Rhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America. OBJECTIVE: To describe outcomes in the CABANA trial as a function of race/ethnicity. METHODS: CABANA randomized 2204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in this analysis, and participants were subgrouped as racial/ethnic minority or non-minority using National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. RESULTS: Of 1280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with non-minorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, had more symptomatic heart failure (37.0% versus 22.0%, respectively), hypertension (92.1% versus 76.8%, respectively), and an ejection fraction

Background: In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Methods: The CABANA trial randomized 2204 patients with AF who were ≥65 years old or II at baseline and form the subject of this article. The CABANA trial’s primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Results: Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction Conclusions: In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508 ; Unique identifier: NCT0091150.

The CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.The purpose of this study was to assess recurrence of AF in the CABANA trial.The authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach.Median age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p 0.001). These findings were not sensitive to the baseline pattern of AF.Catheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).

Background Catheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic vs nonischemic heart failure. Methods We conducted a retrospective, observational cohort study of patients with HF who underwent AF ablation. Outcomes were compared based on HF etiology and included in‐hospital events, symptoms (Mayo AF Symptom Inventory [MAFSI]), and functional status (New York Heart Association class) and freedom from atrial arrhythmias at 12 months. Results Among 242 patients (n = 70 [29%] ischemic, n = 172 [71%] nonischemic), patients with nonischemic cardiomyopathy were younger (mean age 64 ± 11.5 vs 69 ± 9.1, P = .002), more often female (36% vs 17%, P = .004), and had higher mean left‐ventricular ejection fraction (47% vs 42%, P = .0007). There were no significant differences in periprocedural characteristics, including mean procedure time (243 ± 74.2 vs 259 ± 81.8 minutes, P = .1) and nonleft atrial ablation (17% vs 20%, P = .6). All‐cause adverse events were similar in each group (15% vs 17%, P = .7). NYHA and MAFSI scores improved significantly at follow‐up and did not differ according to HF etiology (P = .5; P = .10‐1.00 after Bonferroni correction). There were no significant differences in freedom from recurrent atrial arrhythmia at 12‐months between ischemic (74%) and nonischemic patients (78%): adjusted RR 0.63, 95% confidence interval 0.33‐1.19. Conclusions Catheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic vs nonischemic HF etiology., Catheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic versus nonischemic heart failure. We found that catheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic versus nonischemic HF etiology.

Background: The CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) was a randomized, prospective trial of left atrial catheter ablation versus drug therapy for treatment of atrial fibrillation (AF). As part of CABANA, a prospective imaging substudy was conducted. The main objectives were to describe the patterns of changes in the dimensions of the left atrium and pulmonary veins (PVs), and the relationship between these changes with treatment assignment and clinical outcomes. Methods: Computed tomography or magnetic resonance imaging was acquired at baseline and follow-up in 121 ablation (median follow-up 101 days) and 85 drug patients (median follow-up 97 days). Left atrial volume index, mean PV ostial diameter, and ostial diameters of each PV separately were computed. We examined the relationship between the change from baseline to follow-up with subsequent clinical outcomes (composite of death, disabling stroke, serious bleeding, or cardiac arrest [CABANA primary end point], total mortality or cardiovascular hospitalization, first AF recurrence after the 90-day blanking period, first AF/atrial flutter/atrial tachycardia after the 90-day blanking period) using Cox proportional-hazards models. Results: The median (25th to 75th) change from baseline for left atrial volume index was −7.8 mL/m 2 (−16.4 to 0.2), ablation arm and −3.5 mL/m 2 (−11.4 to 2.6), drug therapy arm. The left atrial volume index decreased in 52.9% of ablation patients versus 40.0% of drug therapy patients. Change for mean PV was −2.7 mm (−4.2 to −1.3) in the ablation arm versus −0.1 mm (−1.5 to 0.8) in the drug therapy arm. Changes in left atrium and PV dimensions had no consistent relationship with the risk of developing the study primary end point. Reductions in left atrial volume index, and in mean PV diameter were associated with decreased risk of AF recurrence. Conclusions: Ablation patients demonstrated more frequent and larger atrial structural changes compared with drug patients. These changes suggest a critical relationship between structural features and AF generation.

Background: Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Methods: CABANA randomized patients with AF age ≥65 years or Results: CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) ( P P =0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62–1.65) in women and 0.73 (95% CI, 0.51–1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51–0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40–0.58] for men; interaction P value=0.060). Conclusions: Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00911508.

Background The CABANA trial compared drug vs ablation therapy yet did not identify a difference in the primary endpoint of death, stroke, severe bleeding, or cardiac arrest or the secondary endpoint of all-cause mortality by intention to treat (ITT) analysis. Nevertheless, there was evidence of improved outcomes and survival in the as-treated and per-protocol analyses. Objectives To determine how the treatment strategies of drug therapy vs ablation impact the atrial fibrillation progression and regression. Methods CABANA randomized 2204 pts with AF ≥65 yrs old or Results Following treatment with ablation, 64% maintained sinus rhythm with elimination of AF, 11% experienced AF regression, and only 7% had progression of AF. In contrast, in those randomized to drug therapy, only 48% experienced maintenance of sinus rhythm, 10% experienced AF regression, and 13% had progression of AF. Moreover, in the drug arm there was a 32% increase in long-standing persistent compared with a 49% reduction in the ablation arm. Conclusion Catheter ablation significantly alters the natural history of atrial fibrillation. Intention to treat analysis reveals that catheter ablation provides superior elimination of AF, protection against AF progression, and dramatically lower risks of long-standing persistent AF. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health

Background: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). Methods: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics and outcomes were determined by manual chart review. Results: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and 3 atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs. 40%, p = 0.003). Cardiac amyloid was diagnosed based on the results of pre-ablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60±15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69±18 ms vs. 57±14 ms, p = 0.36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, while patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, p = 0.014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at one year and 20% at two years. Conclusions: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced stage CA. This article is protected by copyright. All rights reserved.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA,NCT00911508)(1) trial is testing the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art pharmacologic therapy. This international 140-center clinical trial was designed to randomize 2200 patients to a strategy of catheter ablation versus state-of-the-art rate or rhythm control drug therapy. Inclusion criteria include: 1) age> 65, or ≤65 with≥ 1 risk factor for stroke, 2) documented AF warranting treatment, and 3) eligibility for both catheter ablation and≥ 2 anti-arrhythmic or≥ 2 rate control drugs. Patients were followed every 3 to 6 months (median 4 years) and underwent repeat trans-telephonic monitoring, Holter monitoring, and CT/MR in a subgroup of patient studies to assess the impact of treatment on AF recurrence and atrial structure. With 1100 patients in each treatment arm, CABANA is projected to have 90% power for detecting a 30% relative reduction in the primary composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary endpoints include total mortality; mortality or cardiovascular hospitalization; a combination of mortality, stroke, hospitalization for heart failure or acute coronary artery events; cardiovascular death alone; and heart failure death, as well as AF recurrence, quality of life, and cost effectiveness. At a time when AF incidence is rising rapidly, CABANA will provide critical evidence with which to guide therapy and shape health care policy related to AF for years to come.

Background Atrioesophageal fistula formation is a rare but life-threatening complication of atrial fibrillation ablation. Contact force (CF)–sensing catheters improve procedural effectiveness. However, the impact of the implementation of CF-sensing technology on the risk of atrioesophageal fistula formation has not been explored. Objective The purpose of this study was to determine the association between the use of CF-sensing catheters and atrioesophageal fistula development. Methods We searched the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration–approved ablation catheters. Results Among 2689 device reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF-sensing catheters and 13 non–CF-sensing catheters. The percentage of total reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65 of 1202) and 0.9% for non–CF-sensing catheters (13 of 1487) (P Conclusion Atrioesophageal fistula formation accounted for a much higher proportion of reported adverse events with CF-sensing catheters compared with non–CF-sensing catheters. Improved understanding of the relationship between power/force delivery and esophageal damage is needed to minimize the risk of atrioesophageal fistula formation.

The utility of routine transesophageal echocardiography (TEE) to exclude left atrial appendage (LAA) thrombus before atrial fibrillation (AF) ablation in patients treated with nonvitamin K oral anticoagulant (NOAC) therapy is unclear. This single-center retrospective study sought to investigate the incidence of LAA thrombus in patients undergoing routine TEE before AF ablation treated with warfarin or NOAC therapy. We included 937 routine pre-AF ablation TEE procedures performed in patients treated with warfarin (n = 517) or NOAC (n = 420). Patients were anticoagulated without interruption for at least 4 consecutive weeks before the TEE. Patients treated with warfarin had lower LAA velocity and underwent TEE earlier in the study period than those treated with NOAC (p 0.05). The incidence of LAA thrombus was higher in patients treated with warfarin (1.55%, 8 of 517) compared with patients treated with NOAC (0.24%, 1 of 420, p = 0.0473 for difference). No LAA thrombus was identified in NOAC-treated patients with a CHA

This article reviews methods for lesion set assessment during radiofrequency catheter ablation for atrial fibrillation (AF). Pulmonary vein isolation (PVI) is the foundation for AF ablation, but PV reconnection can lead to treatment failure. Testing for entrance block can help confirm PVI, although complex electrograms that consist of both near- and far-field potentials may make assessment of entrance block challenging. Differential pacing maneuvers can help appropriately identify PV potentials. After entrance block has been achieved, pacing within the PVs to demonstrate capture of PV musculature with exit block may also help to confirm completeness of lesion sets for PVI. Employing a waiting period of at least 30 min or administering adenosine or isoproterenol can reveal dormant conduction, warranting adjunctive ablation. Additional techniques to confirm durable PVI include testing the ablation lines for excitability with high amplitude pacing, and automated waveform analysis of local electrogram morphology. Newer techniques like real-time magnetic resonance imaging and acoustic radiation force impulse elastography may have a role in testing the completeness of lesion sets in the future.

Background: Symptomatic sinus node dysfunction (SND) consists of a variety of manifestations, including tachycardia-bradycardia syndrome. Atrial fibrillation (AF) is commonly associated with SND, which complicates the management of both conditions. This paper reviews the epidemiology, pathophysiology, and clinical trial data investigating therapeutic approaches for treatment of patients with both SND and AF. Methods: The authors reviewed articles published in English describing the epidemiology, pathophysiology, and therapeutic approaches for patients with SND and AF. The search was conducted using PubMed. Keywords included: sick sinus syndrome, sinus node dysfunction, atrial fibrillation, pacing, and pulmonary vein isolation. Results: SND affects up to one in five patients with AF. AF can lead to anatomical and electrophysiological remodeling in both atria, including the region of sinoatrial node. Changes including atrial fibrosis, altered calcium channel metabolism, and transformed gene expression have been demonstrated in patients with AF and SND. Nonrandomized clinical trial data have failed to demonstrate whether any pacing strategy can reduce the risk of AF. Pulmonary vein isolation appears to decrease episodes of tachybrady syndrome and sinus pauses. Conclusions: SND affects up to one in five patients with AF. The pathophysiological derangements in gene expression, ion channel metabolism, and alterations in myocardial architecture associated with AF may lead to anatomic and electrical changes in the region of the sinoatrial node. Ablation may improve symptoms associated with SND in patients with AF. Future randomized trials are needed to clarify the epidemiology and optimal management of patients with SND and AF.

Background Prior studies suggest that catheter ablation (ABL) for atrial fibrillation (AF) is a treatment option for patients (pts) with paroxysmal AF (PAF). Pts with persistent (Per) or long-standing persistent (LSP) were routinely excluded from most ABL based clinical trials. The effectiveness of ABL compared to drug therapy (MED) in relation to underlying AF type has not been evaluated in a large randomized clinical trial. Objective To assess the impact of AF type on clinical outcomes of ABL vs. MED in pts with AF. Methods The CABANA trial randomized 2204 pts with AF at 126 sites worldwide to ABL vs. MED with rate or rhythm control drugs. The primary endpoint was a composite of death, disabling stroke, severe bleeding, or cardiac arrest. Key secondary endpoints included mortality and recurrence of AF. Outcomes of ABL vs. MED were compared within subgroups defined by AF type using Intention-to-Treat (ITT) analyses. Results Of the 2204 pts, 946 had PAF, 1042 had Per and 215 presented with LSP. There were baseline differences among AF types in age, gender, HTN, LVH, CHF and NYHA Class. For the primary endpoint, there were no significant differences between ABL and MED in pts with PAF (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.51, 1.31), Per (HR 0.87; 95% CI 0.59, 1.28), or LSP (HR 1.01, 95% CI 0.39, 2.61). Likewise, there were no significant treatment differences in mortality; PAF (HR 0.84; 95% CI 0.46, 1.52), Per (HR 0.90; 95% CI 0.56, 1.46) and LSP (HR 0.67, 95% CI 0.23, 1.94). Post-blanking AF (time to first recurrence) was significantly reduced by ABL compared to MED across all AF types (PAF by 51%), (Per by 47%) and (LSP by 36%). Clinical Characteristics and Outcomes Clinical Outcomes Comparing ABL vs. MED (HR and 95% CI) Interaction p-value Primary Endpoint 0.82 (0.51, 1.31) 0.87 (0.59, 1.28) 1.01 (0.39, 2.61) 0.925 Mortality 0.84 (0.46, 1.52) 0.90 (0.56, 1.46) 0.67 (0.23, 1.94) 0.881 Recurrent AF 0.49 (0.38, 0.62) 0.53 (0.43, 0.65) 0.64 (0.41, 1.01) 0.564 Conclusion Pts with LSP have a lower proportion of women, and a higher proportion with manifestations of heart failure despite lower CHA2DS2VASc scores. By ITT analysis, there is no significant effect of ABL compared to MED in the primary endpoint or mortality in any AF group. However, ABL is more effective than MED for reducing recurrences of AF regardless of AF type, but with a greater effect in PAF vs Per vs LSP. Acknowledgement/Funding NIH, St Jude Medical Foundation and Corporation, Biosense Webster Inc., Medtronic Corporation, and Boston Scientific Corporation

Background Sex-specific outcomes may differ amongst patients receiving catheter ablation for atrial fibrillation (AF). Purpose Assess sex-specific outcomes in the patients randomized to catheter ablation or drug therapy in CABANA. Methods CABANA randomized 2204 pts with AF to catheter ablation or drug therapy (rate/rhythm-control). The outcomes of combined death, disabling stroke, severe bleeding, or cardiac arrest (intention to treat-ITT) or all-cause death were not different. But, ablation significantly improved combined death or CV hospitalization. This analysis compares clinical characteristics by sex and determines sex-specific hazard ratios based on a comparison of ablation vs drug therapy. Results Females were 37.3% of ablation and 37.0% of drug therapy patients. Females were older, more often white race, had less CAD, or sleep apnea, but had higher NYHA Class, higher CHA2DS2VASc, and more often had paroxysmal (v. persistent) AF, and prior AF hospitalization. (Table) HTN, CVA and diabetes were the same (Table). For the CABANA primary endpoint, an ITT comparison of ablation vs. drug therapy, showed a female hazard ratio (HR) of 1.14 (95% confidence interval (CI) 0.70–1.86), and a male HR of 0.74, (95% CI 0.52–1.06). For all-cause mortality, the female HR was 0.75 (95% CI 0.41–1.40) and male HR was 0.91 (95% CI 0.59–1.40) and for all-cause mortality or CV hospitalization, the female HR was 0.90 (95% CI 0.75–1.09) and male HR was 0.79 (95% CI 0.69–0.92). All interaction p values were non-significant. Recurrent AF (post 90-day blanking) was significantly reduced for both females and males: female HR 0.64 (95% CI 0.51–0.82), male HR 0.46 95% CI 0.39–0.56), p=0.035 Clinical Characteristics and Outcomes Baseline Characteristics Female (N=818) Male (N=1385) p-value Age: Median (Q1, Q3) 69 (65, 74) 66 (60, 71) Conclusion Significant sex-specific outcomes differences were not observed. Sex should not be used as a determining factor in selecting patients for AF therapy. Acknowledgement/Funding NIH, St Jude Medical Foundation and Corporation, Biosense Webster Inc., Medtronic Corporation, and Boston Scientific Corporation

Background Pulmonary wall isolation (PWI) is increasingly used as an adjunctive lesion set to compliment pulmonary vein isolation (PVI), especially in patients with persistent atrial fibrillation (AF). The objective was to compare outcomes of catheter ablation in patients with persistent AF undergoing PVI with and without adjunctive PWI. Methods We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF. Subjects were matched using propensity score adjustments. Outcomes were freedom from recurrent atrial arrhythmia and adverse events. Results Among 558 patients who underwent ablation for persistent AF, 78 (14%) underwent PVI + PWI, 255 (46%) underwent PVI, and 225 (40%) underwent PVI + linear ablation. Stratified logistic regression analysis with propensity matching revealed higher odds of recurrent arrhythmia with PVI + PWI when compared to PVI (odds ratio [OR] 2.25, 95% CI 1.08-4.69, P = .030) and when compared to PVI + linear (OR 2.31, 95% CI 1.01-5.28, P = .048). Within the PVI + PWI group, 57.7% of subjects were in normal sinus rhythm at 6 months compared to 73.9% and 72.2% in PVI and PVI + linear groups, respectively. Adverse events were rare, with 19 events total identified across all groups. Conclusions PVI + PWI does not appear to be as effective as PVI or PVI + linear ablation in reducing the recurrence of arrhythmia within 6 months of the index procedure in patients with persistent AF. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF. Condensed Abstract PWI is increasingly used as an adjunctive lesion set to compliment PVI in patients with persistent AF. We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF to compare the outcomes between PVI with and without adjunctive PWI. We found an increased incidence in recurrence of AF and other atrial arrhythmias at 6 months in the PVI + PWI cohort compared to PVI with or without additional linear ablation. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF.

Cardiac perforation is a rare but potentially fatal complication of atrial fibrillation (AF) ablation that can require surgical repair for definitive management. As such, there is controversy regarding the safety of performing AF ablation at centers without on-site cardiothoracic surgery (CTS). The

Background Balloon catheters have been designed to facilitate pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). The visually guided laser balloon (VGLB) employs laser energy to ablate tissue under direct visual guidance. Objectives This study compared the efficacy and safety of VGLB ablation with standard irrigated radiofrequency ablation (RFA) during catheter ablation of AF. Methods Patients with drug-refractory paroxysmal AF were enrolled in a multicenter, randomized controlled study of PV isolation using either the VGLB or RFA (control). The primary efficacy endpoint was freedom from protocol-defined treatment failure at 12 months, including symptomatic AF occurring after the 90-day blanking period. The primary efficacy and safety endpoints were powered for noninferiority. Results A total of 353 patients (178 VGLB, 175 control) were randomized at 19 clinical sites. The mean procedure, ablation, and fluoroscopy times were longer with VGLB compared with controls. The primary efficacy endpoint was met in 61.1% in the VGLB group versus 61.7% in controls (absolute difference −0.6%; lower limit of 95% confidence interval [CI]: −9.3%; p = 0.003 for noninferiority). The primary adverse event rate was 11.8% in the VGLB group versus 14.5% in controls (absolute difference −2.8%; upper limit of 95% CI: 3.5; p = 0.002 for noninferiority), and was mainly driven by cardioversions. Diaphragmatic paralysis was higher (3.5% vs. 0.6%; p = 0.05), but PV stenosis was lower (0.0% vs. 2.9%; p = 0.03) with VGLB. Conclusions Despite minimal prior experience, the safety and efficacy of VGLB ablation proved noninferior to RFA for the treatment of paroxysmal AF. (Pivotal Clinical Study of the CardioFocus Endoscopic Ablation System–Adaptive Contact [EAS-AC] [HeartLight] in Patients With Paroxysmal Atrial Fibrillation [PAF] [HeartLight]; NCT01456000 )

Restoration of sinus rhythm (SR) in patients with atrial fibrillation/atrial flutter (AF/AFL) is limited principally to direct current cardioversion. The multi-ion channel blocker vanoxerine may prove an effective alternative.The purpose of this study was to assess vanoxerine, a 1,4-dialkylpiperazine derivative, for acute conversion of recent-onset, symptomatic AF and AFL.One hundred four subjects with symptomatic AF/AFL for7 days were randomized sequentially to single oral doses of vanoxerine 200, 300, and 400 mg or placebo. Holter monitors were examined for conversion to SR and proarrhythmia through ≥24 hours.Conversion to SR was dose related: 18.2%, 44.0%, and 52.0% within 4 hours, and 59.1%, 64.0%, and 84.0% within 24 hours, for the 200-, 300-, and 400-mg groups, respectively. This was significantly higher than placebo for the 300- and 400-mg groups within 4 hours (12.5% for placebo; P = .0138 and P = .0028, respectively) and for all doses within 24 hours (31.3% for placebo; P = .0421, P = .0138, P = .0001 for 200-, 300-, and 400-mg vanoxerine groups, respectively). Although vanoxerine caused significant dose-dependent QTcF (QT correction by Fridericia) prolongation, monomorphic or polymorphic ventricular tachycardia did not occur. Adverse events were mild and self-limited, with only the highest dose having a greater frequency than placebo.Oral vanoxerine converted AF/AFL to SR at a high rate, was well tolerated, and caused no ventricular proarrhythmia.

The cryothermy ablation balloon catheter was developed to facilitate pulmonary vein (PV) isolation to treat atrial fibrillation (AF). The STOP-AF (Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [[NCT00523978][1]]) trial reported that ablation with

AIMS: To assess whether obstructive sleep apnea (OSA) was associated with increased rotor burden among atrial fibrillation (AF) patients. METHODS AND RESULTS: We studied 33 consecutive patients who were scheduled for focal impulse and rotor modulation (FIRM) ablation at our institution to describe the mapping, ablation, and outcomes, among patients with and without OSA. Patients underwent biatrial FIRM mapping in AF with ablation of stable rotors in addition to conventional ablation lesion sets. Differences between groups were tested with student’s t-tests and Fisher’s exact tests, as appropriate. Survival analyses were performed using the Kaplan–Meier method. Twelve of the 33 (36%) patients had OSA and 8 (66%) used continuous positive airway pressure ventilation (CPAP). Obstructive sleep apnea patients had a higher body mass index (BMI) (33.6 vs. 28.8 kg/m(2), P = 0.01) and were more commonly on beta blockers (67% vs. 29%, P = 0.03) but were otherwise similar regarding baseline characteristics, medication use, and prior AF treatments, including antiarrhythmic drugs and prior ablation. Focal impulse and rotor modulation mapping demonstrated increased rotor burden in the OSA patients (2.6 ± 0.9 vs. 2.0 ± 1.0, P =0.03). The increased rotor burden was more evident in the right atrium (RA) (1.0 ± 0.7 vs. 0.5 ± 0.7, P =0.04 compared with left atrium (1.7 ± 0.8 vs. 1.4 ± 0.7, P = 0.15). There was no correlation between BMI and total number of rotors (r = 0.0961, P = 0.59). Among the population of patients with OSA, CPAP therapy was associated with a lower number of RA rotors (0.8 ± 0.7 vs. 1.5 ± 0.6, P = 0.05) but no significant difference in overall rotors (P = 0.33). CONCLUSION: Obstructive sleep apnea patients demonstrate increased rotor prevalence, driven predominantly by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.

Background: Visual confirmation of radiofrequency ablation (RFA) lesions during clinical cardiac ablation procedures could improve procedure efficacy, safety, and efficiency. It was previously shown that acoustic radiation force impulse (ARFI) imaging can identify RFA lesions in vitro and in vivo in an animal model. This is the “first-in-human” feasibility demonstration of intracardiac ARFI imaging of RFA lesions in patients undergoing catheter ablation for atrial flutter (AFL) or atrial fibrillation (AF). Methods and Results:Patients scheduled for right atrial (RA) ablation for AFL or left atrial (LA) ablation for drug refractory AF were eligible for imaging. Diastole-gated intracardiac ARFI images were acquired usingoneoftwoequipmentconfigurations:(1)aSiemensACUSONS2000 TM ultrasoundscannerand8/10Fr AcuNav TM ultrasound catheter, or (2) a CARTO 3 TM integrated Siemens SC2000 TM and 10Fr SoundStar TM ultrasound catheter. A total of 11 patients (AFL = 3; AF = 8) were imaged. ARFI images were acquired of ablation target regions, including the RA cavotricuspid isthmus (CTI), and the LA roof, pulmonary vein ostia, posterior wall, posterior mitral valve annulus, and the ridge between the pulmonary vein and LA appendage. ARFI images revealed increased relative myocardial stiffness at ablation catheter contact sites after RFA and at anatomical mapping-tagged RFA treatment sites. Conclusions: ARFI images from a pilot group of patients undergoing catheter ablation for AFL and AF demonstrate the ability of this technique to identify intra-procedure RFA lesion formation. The results encourage further refinement of ARFI imaging clinical tools and continued investigation in larger clinical trials. (J Cardiovasc Electrophysiol, Vol. pp. 1-9)

Importance Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15];P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21];P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93];P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60];P Conclusions and Relevance Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration ClinicalTrials.gov Identifier:NCT00911508

Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain.To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF.An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017.Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096).Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.3 points).Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, -1.7 points [95% CI, -2.3 to -1.2]; P .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, -1.5 points [95% CI, -2.0 to -1.1]; P .001).Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation.ClinicalTrials.gov Identifier: NCT00911508.

Dabigatran is approved for prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). The safety and effectiveness of periprocedural dabigatran in ablation for AF are unknown. We performed a meta-analysis of all studies comparing periprocedural dabigatran with warfarin for anticoagulation in AF ablation. Studies of >100 patients with post-procedure follow-up were included. Outcomes were compared by calculating maximum likelihood estimates with confidence intervals. The co-primary endpoints were neurological events and major bleeding. Ten cohort studies were included, including a total of 1,501 patients receiving dabigatran and 2,356 receiving warfarin. The mean age was 59–64 years and inclusion of women varied (10–33 %). Intra-procedural unfractionated heparin and irrigated ablation catheters were used routinely. Adverse events were low overall; however, the dabigatran group demonstrated a numerical excess of neurological events (10/1,501 [0.7 %] versus 4/2,356 [0.2 %]), but equivalent major bleeding outcomes (24/1,501 [1.6 %] versus 40/2,356 [1.7 %]). In the meta-analysis, there was a nonsignificant trend towards higher rates of the composite primary endpoints (any neurological event or major bleeding) in the dabigatran group. Dabigatran demonstrated a significantly higher rate of neurological events (estimated absolute risk difference 0.0047, 95 % confidence interval 0.0007 to 0.0099). Compared with warfarin, dabigatran may be associated with a higher frequency of periprocedural neurological events following radiofrequency ablation of AF. Randomized clinical trials are needed to definitively assess the safety and efficacy of novel oral anticoagulant use for periprocedural anticoagulation for ablation of AF.

Despite advances in ablation technology, many patients experience recurrent atrial fibrillation (AF) after radiofrequency ablation. Although estimates vary, the overall 1-year drug-free success for AF ablation is estimated at 40% to 60% for a single procedure and 70% for multiple procedures.1 The cornerstone of conventional AF ablation is pulmonary vein isolation (PVI), and in clinical practice, the most common PVI technique involves creating circular radiofrequency lesions in a point-by-point fashion around the PV ostia/antra.2 However, conventional radiofrequency ablation can be difficult and time-consuming, has less than outstanding efficacy, and can be associated with potentially serious complications, such as steam pops, perforation, tamponade, and thrombus formation, which can lead to thromboembolic events. Given the limitations of conventional radiofrequency ablation, there has been ongoing development of new technologies to facilitate the safety and efficacy of lesion formation and durability. This review will summarize several recent advancements in catheter technology for AF ablation aimed at improving lesion formation (Figure 1). Figure 1. Summary of recent innovations in lesion formation. In radiofrequency ablation, the contact force (CF) between the ablation electrode and the atrial wall is a major determinant of lesion size and durability.3,4 Insufficient CF can result in inadequate lesion formation and higher rates of PV reconnection.5 However, excessive CF can result in complications, such as perforation.6 Therefore, monitoring CF would be expected to maximize ablation efficacy and improve safety. Until recent years, CF has been monitored indirectly using a combination of visual observation of catheter tip motion, tactile feedback, local electrogram attenuation, impedance monitoring, and in some laboratories, intracardiac echocardiogaphy. Although widely used, these methods are a poor surrogate for CF.4,7,8 Recently, ablation catheters that can directly measure CF have become available in the United States. A spring-coupled catheter (SmartTouch) was …

Surgical or modified Maze procedures have been promoted to treat atrial fibrillation (AF); however, few randomized controlled clinical trials (RCTs) examine their outcomes. The purpose of this meta-analysis is to compare the efficacy of surgical Maze procedures performed concomitantly with referral cardiac surgery versus pharmacologic therapy for the treatment of AF. We searched MEDLINE, Cochrane database, FDA web-portal, and clinicaltrials.gov for all RCTs comparing surgical Maze procedures with medical therapy for sinus rhythm maintenance. Primary outcomes were either freedom from AF within 12 months postprocedure off antiarrhythmic drug (AAD), or freedom from AF while taking an AAD. Secondary outcomes included operative mortality, all-cause mortality, hospital length of stay, and postoperative complications. Both fixed- and random-effects models were used for a meta-analysis of 9 randomized controlled trials (n = 472, of which 249 underwent a Maze procedure and 213 underwent referral surgery alone). The surgical Maze procedure significantly increased the odds of freedom from AF within 12 months compared with cardiac surgery alone (OR 5.22, 95% CI 1.71-15.88). There was significant heterogeneity among the trials for freedom from AF (chi-square = 15.98 for 4 degrees of freedom, P= 0.003). Among the two studies that fully reported AAD use, there was no evidence of improved survival free from AF and AAD therapy (OR 1.78, 95% CI 0.73-4.34). Among patients with valvular AF, surgical Maze procedures are associated with a decrease in AF one year postprocedure without significant increase in mean length of hospital stay, perioperative complications, operative, or all-cause mortality. Large RCTs defining rates of freedom from AF without AADs postprocedure, are still needed to evaluate outcomes and determine the appropriate role for surgical Maze procedures in the management of AF.

Esophageal injury is a rare but serious complication of catheter ablation for atrial fibrillation using radiofrequency energy. Recent studies have begun to identify variables that may determine heat transfer to and thermal injury of the esophagus. There is significant variability in the relationship between the esophagus and left atrium among individuals. New imaging techniques can facilitate assessment of esophagus position relative to intended ablation targets. Strategies to minimize the risk of esophageal injury include avoidance of ablation near the esophagus, titration of RF energy delivery at the posterior left atrial endocardium, and the use of alternative ablation methods.

Introduction: Left atrial radiofrequency catheter ablation (RFA) is gaining acceptance as treatment for drug-refractory atrial fibrillation (AF). This therapy has been associated with esophageal injury and atrioesophageal fistula formation causing death. Methods: We describe 3 patients undergoing catheter ablation for AF during real-time monitoring of luminal esophageal temperature. Results: We observed heating of the esophagus during short duration low power RFA, at either the left or right pulmonary vein ostia. Cryoablation at the pulmonary vein ostium in one patient resulted in esophageal cooling. Furthermore, we observed that fluoroscopic localization of the ablation catheter at a site apparently distant from the esophagus is not adequate to assure avoidance of ablation-induced esophageal heating. Conclusions: Real-time monitoring of luminal esophageal position and temperature is feasible, enhances recognition of esophageal heating, and may add useful information beyond that provided by fluoroscopic assessment of esophageal position. There is a potential role for esophageal monitoring to help avoid thermal injury to the esophagus during catheter ablation for atrial fibrillation.

Warfarin is underused for stroke prevention in atrial fibrillation (AF). Previous studies addressing this have lacked longitudinal assessment. This study sought to characterize contemporary warfarin use in new-onset AF and evaluate its change over time. It was hypothesized that AF recurrence has an important influence on warfarin use patterns. One thousand five adults from 17 centers in the United States and Canada were enrolled into a prospective observational registry after their first documented episodes of AF. Detailed demographic, clinical history, and management data were collected on all subjects at enrollment, including medication use. Patients were followed at regular intervals for interim events and changes in AF management. Warfarin use at baseline and last follow-up (mean 25 +/- 8 months) after enrollment was modeled using multivariate analysis. Initially, 65% of subjects were prescribed warfarin, but only 44% were taking it at 30 months. Even in "ideal" candidates for warfarin, the rate of warfarin prescription decreased from 70% at baseline to 50% at 30 months. Stroke risk factors, including hypertension, congestive heart failure, valvular heart disease, and previous stroke or transient ischemic attack were significant predictors of warfarin prescription at baseline. At last follow-up, the relation between AF recurrence and warfarin use (odds ratio 2.3, 95% confidence interval 1.6 to 3.1) was stronger than that for any individual stroke risk factor. In conclusion, predictors of warfarin use in patients with AF include AF recurrence and selected stroke risk factors. The discontinuation of warfarin in a large number of patients with AF over time is a cause for concern in light of data from recent clinical trials.

Rationale and objectivesGeometric analysis of the left atrium and pulmonary veins is important for assessing reverse structural remodeling following cardiac ablation therapy. Most volumetric analysis techniques, however, require laborious manual tracing of image cross-sections. Pulmonary vein diameters are typically measured at the junction between the left atrium and pulmonary veins, called the pulmonary vein ostia, with manually drawn lines on volume renderings or in image slices. In this work, we describe a technique for making semi-automatic measurements of left atrial volume and pulmonary vein diameters from high resolution CT scans and demonstrate its use for analyzing reverse structural remodeling following cardiac ablation therapy. MethodsThe left atrium and pulmonary veins are segmented from high-resolution computed tomography (CT) volumes using a 3D volumetric approach and cut planes are interactively positioned to separate the pulmonary veins from the body of the left atrium. Left atrial volume and pulmonary vein ostial diameters are then automatically computed from the segmented structures. Validation experiments are conducted to evaluate accuracy and repeatability of the measurements. Accuracy is assessed by comparing left atrial volumes computed with the proposed methodology to a manual slice-by-slice tracing approach. Repeatability is assessed by making repeated volume and diameter measurements on duplicated and randomized datasets. The proposed techniques were then utilized in a study of 21 patients from the Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) pilot study who were scanned both before and approximately 3 months following ablation therapy. ResultsIn the high resolution CT scans the left atrial volume measurements show high accuracy with a mean absolute difference of 2.3?1.9cm3 between volumes computed with the proposed methodology and a manual slice-by-slice tracing approach. In the intra-rater repeatability study, the mean absolute difference in left atrial volume was 4.7?2.5cm3 and 4.4?3.4cm3 for the two raters. Intra-rater repeatability for pulmonary vein diameters ranged from 0.9 to 2.3mm. The inter-rater repeatability for left atrial volume was 5.8?5.1cm3 and inter-rater repeatability for pulmonary vein diameter measurements ranged from 1.4 to 2.3mm. In the patient study, significant (p

Objectives The purpose of this study was to correlate patient-reported symptoms of atrial fibrillation with the underlying rhythm. Background The reliability of patient-reported symptoms as a marker of atrial fibrillation recurrence has not been well studied. Methods This prospective multicenter trial correlated the recurrence of atrial tachyarrhythmias with symptoms in patients with a history of atrial fibrillation and a standard indication for permanent pacing. Pacemaker-detected atrial tachyarrhythmia events were correlated with symptoms. Patients logged symptomatic events into the device's memory via an external manual activator. Patients were followed for 12 months and were contacted weekly to ensure compliance with activator usage. Episodes were classified as symptomatic atrial tachyarrhythmia, asymptomatic atrial tachyarrhythmia, or symptomatic nonatrial tachyarrhythmia depending on concordance between patient symptoms and the rhythm. Results Forty-eight patients underwent implantation of a DDDRP pacemaker and were followed for 12 ± 2 months. A median of 25.0 (4.0–55.8) symptomatic events attributed to atrial fibrillation. A median of 1.0 (0.0–10.0) symptomatic atrial tachyarrhythmia episodes were documented during follow-up. Symptoms related to atrial fibrillation were reported in 6% of atrial tachyarrhythmia episodes identified by the pacemaker. The probability that symptoms were associated with an atrial tachyarrhythmia (positive predictive value) was 17%. The ventricular rate between symptomatic and asymptomatic atrial tachyarrhythmia events was not significantly different. Conclusions Among patients with symptomatic bradycardia and a history of atrial fibrillation, symptoms of atrial fibrillation often were not associated with documented atrial tachyarrhythmias, and more than 90% of atrial tachyarrhythmias were clinically silent.

Evidence derived from in vivo experimental studies performed with angiotensin converting enzyme inhibitors (ACEi) indicates that these agents are capable of modulating the process of cardiac hypertrophy and fibrosis. The antifibrotic actions of ACEi are thought to be derived from their capacity to block the production of angiotensin II and, thus, its action on the cardiac fibroblast. However, in contrast to rat hearts, human myocardium has low levels of angiotensin II receptors. Evidence indicates that enhanced bradykinin (BK) levels result from the action of ACEi. In vivo data derived from the use of the BK blocker HOE140 suggests a role for BK in repressing the process of cardiac hypertrophy and fibrosis. Little is known as to the abundance of angiotensin II and BK receptors in human cardiac fibroblasts. Data presented in this study indicates that in cultured human cardiac fibroblasts there is apparently few angiotensin II receptors whereas as in other species there is evidence for the presence of BK receptors. Further studies need to be performed to establish the potential role that BK plays in modulating human cardiac fibroblast function.

Recurrence of atrial fibrillation after transcatheter ablation (TCA) is common because there is no imaging modality that can visually confirm the presence of radiofrequency ablation (RFA) lesions. We have previously shown that acoustic radiation force impulse (ARFI) imaging can visualize the relative tissue stiffness changes caused by RFA. The objective of this study was to determine if intra-procedurally acquired ARFI images could identify RFA lesions. In 8 canines, an integrated ARFI imaging-electroanatomical mapping (EAM) system was used to map the geometry of the right atrium and acquire ARFI images along an inter-caval line before and after RFA. RF-energy delivery sites were marked in the EAM geometry to guide the ARFI imaging plane to RFA lesion locations. The ARFI images were randomized and three separate reviewers read the images for the presence of RFA lesion. The majority assessment for each ARFI image was counted in a 2 × 2 contingency table according to the presence/absence of a RFA treatment marker in the EAM geometry at the ARFI imaging plane. EAM guided intra-procedure ARFI imaging of RFA treatment sites. Reviewers of the ARFI images identified RFA lesion with a high sensitivity (96.3%) and specificity (93.2%). Incorporating an integrated ARFI imaging-EAM system into TCA for the visualization of RFA lesions could potentially improve the procedure efficacy.

Background Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease postprocedure atrial fibrillation recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff RFA-treated myocardium. Objective To determine whether intraprocedure ARFI images can identify RFA-treated myocardium in vivo. Methods In 8 canines, an electroanatomical mapping–guided intracardiac echo catheter was used to acquire 2-dimensional ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the intracardiac echo transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, noncontiguous lesion, or contiguous lesion. For comparison, 3 separate reviewers confirmed RFA lesion presence and contiguity on the basis of functional conduction block at the imaging plane location on electroanatomical activation maps. Results Ten percent of ARFI images were discarded because of motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesions had 75.3% specificity and 47.1% sensitivity. Conclusions Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation.

BACKGROUND Pharmacological control of rapid ventricular response to atrial fibrillation may be difficult in some patients. Alternative treatments, including curative surgery or atrioventricular (AV) node ablation with pacemaker implantation, have significant potential morbidity. In view of evidence that dual AV nodal physiology may exist in a significant percentage of the population, even in those without AV nodal reentrant tachycardia, we postulated that control of ventricular response might be achieved by radiofrequency (RF) catheter ablation in the region of the AV nodal slow pathway with its short refractory period. METHODS AND RESULTS Ten patients underwent attempted AV node modification using a 4-mm-tipped electrode catheter positioned in the middle or posterior septum, between the His bundle and coronary sinus ostium on the tricuspid valve annulus. RF energy was applied at 16 to 30 W for up to 60 seconds, until average ventricular response fell below 100 beats per minute. Reduction of maximal ventricular response below 120 beats per minute was confirmed with atropine 1 mg IV. If required, additional ablations were performed progressively more posteriorly up to the coronary sinus ostium. Patients with successful AV node modification were discharged off AV node-blocking drugs and followed in the clinic at regular intervals. Twenty-four-hour ambulatory ECG recordings and/or treadmill stress tests were obtained before and after ablation for statistical comparison of maximum ventricular rate. Resting average ventricular rate was determined during electrophysiology study before and after ablation. In 7 of 10 patients (70%), maximum ventricular rate was reduced from a mean of 164 +/- 12 to 123 +/- 16 beats per minute (P < .01) and average ventricular rate from a mean of 128 +/- 11 to 83 +/- 10 beats per minute after ablation. Mean minimum ventricular rate was 54 +/- 11 beats per minute after ablation. These 7 patients have remained symptom free from rapid ventricular response for a mean of 14 +/- 8 months (range, 1 to 22). Three remain off all AV node-blocking drugs, 3 remain on digoxin alone, which was previously ineffective, and 1 remains on a beta-blocker for angina. In the 3 patients who did not respond to AV node modification, complete AV node ablation and permanent pacemaker implantation was performed in 2 and DC cardioversion after amiodarone loading was performed in 1. CONCLUSIONS RF catheter modification of AV node conduction is effective in controlling rapid ventricular response to atrial fibrillation in a significant percentage of medically refractory patients. A possible mechanism of RF modification of AV node conduction is AV nodal slow pathway ablation. Large-scale clinical trials will be needed to determine the overall efficacy and safety of this technique.

In the results section, under ‘Secondary Endpoints’ the mean procedural, fluoroscopy, and RF energy times were incorrectly reported. The correct times should be as follows: Mean Procedural time for PVI v. PVI + CFAE: 202.9 +/- 71.3 min v. 278.5 +/- 84.9 min Mean Fluoroscopy time for PVI v. PVI + CFAE: 59.5 +/- 22.2 min v. 79.3 +/- 29.2 min Mean RF Energy time for PVI v. PVI + CFAE: 69.7 +/- 33.4 min v. 92.8 +/- 39.2 min The p values and the conclusions are not affected. The authors apologize for this error.

In the pancreatic acinar cell, hormonal stimulation causes a rise in the intracellular free Ca2+ concentration by activating the inositol 1,4,5-trisphosphate-mediated release of Ca2+ from intracellular stores (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205). The released Ca2+ is, for the most part, extruded from the cell, necessitating a mechanism for Ca2+ entry and reloading of intracellular Ca2+ stores (Putney, J. W., Jr. (1990) Cell Calcium 11, 611-624; Rink, T. J. (1990) FEBS Lett. 268, 381-385). However, neither the mechanism of depletion-activated Ca2+ entry nor the signal that activates it is known. We report here that a sustained inward current of depletion-activated Ca2+ entry can be measured in pancreatic acinar cells using patch-clamp recording methods. Furthermore, the current can be blocked by an inhibitor of guanylyl cyclase, can be reactivated by 8-bromo-cGMP after inhibition, and can be activated in the absence of Ca2+ depletion by perfusing the cell with cGMP, but not cAMP. Intracellular perfusion with 1,3,4,5-inositol tetrakisphosphate did not activate an inward current, whereas perfusion with 2,4,5-inositol trisphosphate did activate an inward current. We conclude that cGMP may be an intracellular messenger that regulates depletion-activated Ca2+ entry.

PURPOSE OF REVIEW Atrial fibrillation is increasingly prevalent among older adults and is a major contributor to morbidity in this population due to associated strokes, heart failure, and quality of life impairment. Catheter ablation for atrial fibrillation is demonstrated to be superior to antiarrhythmic therapy for the control of symptomatic and medically refractory atrial fibrillation, but its safety and efficacy in the elderly are not well understood. Clinical trials to guide the optimal management strategy in this population are lacking. RECENT FINDINGS Several nonrandomized clinical studies have recently addressed the issue of catheter ablation in the elderly and show favorable rates of success. Unfortunately, these studies are limited by the relatively small numbers of patients examined and often by their single-center and retrospective nature. SUMMARY Before the results of these studies can be extrapolated, data from larger cohorts of elderly patients followed prospectively are desperately needed.

Aims Although useful, percutaneous left atrial ablation for pulmonary vein isolation (PVI) does not eliminate atrial fibrillation (AF) in all patients. The ablation of complex fractionated atrial electrograms (CFAEs) has been proposed as an adjunctive strategy to improve the maintenance of sinus rhythm after PVI. Our objective was to analyse the efficacy of adjunctive CFAE ablation. Methods and results We meta-analysed six randomized controlled trials (total, n = 538) using random-effects modelling to compare PVI ( n = 291) with PVI plus CFAE ablation (PVI + CFAE) ( n = 237). The primary outcome was freedom from AF or other atrial tachyarrhythmias (ATs) after a single ablation with or without antiarrhythmic drugs. Following a single ablation, PVI + CFAE improved the odds of freedom from any AF/AT compared with PVI alone (odds ratio 2.0, 95% confidence interval 1.04–3.8, P = 0.04) at ≥3-month follow-up. There was moderate heterogeneity among trials ( I 2= 63.0%). Complex fractionated atrial electrogram ablation significantly increased mean procedural (178.5 ± 66.9 vs. 331.5 ± 92.6 min, P < 0.001), mean fluoroscopy (59.5 ± 22.2 vs. 115.5 ± 35.3 min, P < 0.001), and mean radiofrequency (RF) energy application times (46.9 ± 36.6 vs. 74.4 ± 43.0 min, P < 0.001). Conclusions Pulmonary vein isolation followed by adjunctive CFAE ablation is associated with increased freedom from AF after a single procedure. Adjunctive CFAE ablation increased procedural, fluoroscopy, and RF application times, and the risk/benefit profile of adjunctive CFAE ablation deserves further evaluation with additional studies and longer-term follow-up.

Cardiovascular magnetic resonance imaging (cMRI) may provide a noninvasive method to test for pulmonary vein (PV) isolation after ablation for atrial fibrillation (AF) by detecting changes in PV contraction.PV contraction (the maximal percentage change in PV cross-sectional area [CSA] during the cardiac cycle) measured 1 month before and 2 months after PV isolation was compared in 63 PVs from 16 patients with medically refractory AF. Repeat cMRI imaging and invasive catheter mapping was performed prior to repeat PV ablation in 50 PVs from 14 additional patients with recurrent AF. Contraction in PVs with sustained isolation after the initial ablation was compared to contraction in PVs with electrical reconnection to adjacent atrium. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff PV contraction value for prediction of PV-atrial reconnection after ablation. The cutoff value was then prospectively tested in 40 PVs from 12 additional patients.PV contraction decreased after AF ablation (22.4 ± 10% variation in CSA before ablation vs 10.1 ± 8% variation in CSA after ablation, P0.00001). PVs with sustained isolation on invasive mapping contracted less than PVs with electrical reconnection to adjacent atrium (13.7 ± 10.6% vs 21.4 ± 9.3%, P = 0.021). PV contraction produced a c-index of 0.74 for prediction of PV-atrial reconnection after ablation and17% variation in PV CSA predicted reconnection with a sensitivity of 84.6% and specificity of 66.7%.PV contraction is reduced by ablation. PV contraction measurement may provide a noninvasive method to test for PV isolation after ablation procedures.

LAA Thrombus Among Anticoagulated AF Patients. Introduction: Catheter-directed atrial fibrillation (AF) ablation is contraindicated among patients with left atrial appendage (LAA) thrombus. The prevalence of LAA thrombus among fully anticoagulated patients undergoing AF ablation is unknown. Methods and Results: We retrospectively evaluated the prevalence of LAA thrombus among 192 consecutive patients undergoing AF ablation between July 2006 and January 2009. Seven of 192 patients (3.6%) had evidence of thrombus on transesophageal echocardiogram (TEE) despite being fully anticoagulated on warfarin (international normalized ratio [INR] 2–3) for 4 consecutive weeks prior to echocardiogram. Univariate analysis demonstrated that structural heart disease, large left atrial dimension, and number of AF ablations were associated with thrombus. Three patients with thrombus had paroxysmal AF with normal LV function. Conclusion: Despite full anticoagulation, 3.6% of patients undergoing AF ablation had LAA thrombus. We recommend that all patients, regardless of LV function or left atrial size, should undergo preprocedural TEE to exclude the presence of LAA thrombus. (J Cardiovasc Electrophysiol, Vol. 21, pp. 849-852, August 2010)

BACKGROUND Recent studies of human type 1 atrial flutter demonstrated reentry in the right atrium and an area of slow conduction in the low posteroseptal right atrium. Direct-current catheter ablation of this area has been only moderately successful in preventing recurrence. Therefore, we performed endocardial activation mapping and entrainment pace mapping during atrial flutter to determine the critical site for radiofrequency ablation of this arrhythmia. METHODS AND RESULTS Twelve consecutive patients (seven men and five women; age, 21-73 years) with type 1 atrial flutter (mean cycle length, 253 +/- 39 msec) underwent right atrial endocardial activation and entrainment pace mapping using standard transvenous catheter techniques to localize the atrial flutter reentrant circuit, the area of slow conduction, and the exit site from the area of slow conduction. Upon identifying appropriate sites, radiofrequency energy (16-29 W) was applied via a 4-mm tipped catheter. Activation mapping of atrial flutter revealed a counterclockwise reentrant wave front originating just inferior or posterior to the coronary sinus ostium, proceeding superiorly in the atrial septum to the right atrial free wall, then inferiorly toward the tricuspid annulus and finally medially between the inferior vena cava and the tricuspid annulus, where low-amplitude fragmented electrical activity was noted. Entrainment pace mapping from this area produced an exact P wave match to atrial flutter on 12-lead ECG with a long (greater than 40 msec) stimulus-to-P interval indicating slow conduction, whereas pacing just inferior or posterior to the coronary sinus ostium produced an exact P wave match with a short stimulus-to-P interval (less than 40 msec), presumably identifying the exit site from the area of slow conduction. Radiofrequency energy (one to 14 applications) was effective in terminating and preventing reinduction of atrial flutter in 10 patients. In two patients, atrial flutter was not terminated during radiofrequency energy application but during subsequent pacing attempts. Sites where ablation was successful, located just inferior or posterior to the coronary sinus ostium, were characterized by discrete electrograms with activation times of -20 to -50 msec before P wave onset and exact entrainment pace maps with a stimulus-to-P interval of 20 to 40 msec, consistent with the exit site from the area of slow conduction. Follow-up (mean, 16 +/- 9 weeks; range, 2-31 weeks) revealed recurrence of the original atrial flutter in two patients, one of whom underwent repeat ablation without further recurrence, self-limited infrequent recurrence of a new atrial flutter or atrial fibrillation in three suppressed by beta-blocker or digoxin, and no recurrence in seven. CONCLUSIONS 1) Radiofrequency energy applied to a critical area in the atrial flutter reentrant circuit, inferior or posterior to the coronary sinus ostium, will terminate and prevent arrhythmia reinduction. 2) Long-term follow-up in a larger series of patients will be required to confirm efficacy of this technique, although short-term results look promising.

The currently available sudden cardiac death (SCD) risk prediction tools fail to identify most at-risk patients and cannot delineate a specific patient's SCD risk. We sought to develop a tool to improve the risk stratification of patients with coronary artery disease. Clinical, demographic, and angiographic characteristics were evaluated among 37,258 patients who had undergone coronary angiography from January 1, 1985 to May 31, 2005, and who were found to have at least one native coronary artery stenosis ofor =75%. After a median follow-up of 6.2 years, SCD had occurred in 1,568 patients, 14,078 patients had died from other causes, and 21,612 patients remained alive. A Cox proportional hazards model identified 10 independent patient characteristic variables significantly associated with SCD. A simplified model accounting for 97% of the predictive capacity of the full model included the following 7 variables: depressed left ventricular ejection fraction, number of diseased coronary arteries, diabetes mellitus, hypertension, heart failure, cerebrovascular disease, and tobacco use. The Duke SCD risk score was created from the simplified model to predict the likelihood of SCD among patients with coronary artery disease. It was internally validated with bootstrapping (c-index = 0.75, chi-square = 1,220.8) and externally validated in patients with ischemic cardiomyopathy from the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) database (c-index = 0.64, chi-square = 14.1). In conclusion, the Duke SCD risk score represents a simple, validated method for predicting the risk of SCD among patients with coronary artery disease and might be useful for directing treatment strategies designed to mitigate the risk of SCD.

Background: Although atrial fibrillation or flutter (AF) is thought to occur commonly after pulmonary transplantation, little is known about the epidemiology, risk factors, or clinical significance of arrhythmia in this population. The aim of the current study was to determine the incidence, clinical predictors, and associated morbidity of AF after lung transplant. Methods: The records of 200 consecutive adult patients who underwent lung transplantation at a single institution from August 1998 to June 2002 were studied. Multivariate logistic regression analysis was performed to define the predictors for posttransplant AF. Results: Indications for transplant included COPD in 43%, cystic fibrosis in 18%, and idiopathic pulmonary fibrosis (IPF) in 17%. The transplants were bilateral (79%) or single lung (21%). The mean age of the patients was 50 years (range, 19 to 66 years; median, 54 years). Postoperative AF within 14 days of transplant occurred in 78 patients (39%), with a mean onset of 3.8 3.0 days ( SD). Significant predictors of AF were as follows: age > 50 years (odds ratio [OR], 2.1; p 0.01), IPF (OR, 2.3; p 0.03), existing coronary disease (OR, 2.0; p 0.009), enlarged left atrium (LA) on echocardiography (OR, 3.9; p 0.05), and number of postoperative vasopressors (OR, 1.5; p 0.03). Patients with AF had longer hospital stays (32.4 60.0 days vs 17.5 24.1 days, p 0.04), were more likely to undergo tracheostomy (OR, 3.6; p 0.0003), and had more in-hospital deaths (OR, 5.7; p 0.0005) than patients without AF. Conclusions: AF is a frequent complication after lung transplant. Advanced age, IPF, known coronary disease, enlarged LA, and use of postoperative vasopressors increase the risk for developing AF. The development of posttransplant AF is associated with significantly prolonged hospital stay and increased mortality. Prospective studies designed to prevent posttransplant AF are needed to clarify the extent to which AF impacts on posttransplant outcomes. (CHEST 2004; 126:496 –500)