Packer, Douglas L.

AbstractAimsTreatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an antiarrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF).Methods and resultsA total of 218 treatment naive patients with symptomatic PAF were randomized (1 : 1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was ≥1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR = 0.48, P = 0.01). There were no group differences in the time-to-first (HR = 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR = 0.40, P < 0.001).ConclusionsCryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.

Abstract Background Unexpected variations in treatment benefits by geographic region raise questions about the generalizability of findings from international clinical trials. Purpose Investigate the outcome of catheter ablation vs drug therapy in CABANA patients with AF treated at North American (NA) compared with non-NA sites, a pre-specified comparison. Methods CABANA randomized 2204 symptomatic patients with atrial fibrillation (AF) to ablation vs drug therapy at 126 centers in 10 countries. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Results There were 1285 patients enrolled at 85 NA sites, and 919 at 45 non-NA sites. At baseline, NA and non-NA patients differed significantly with regard to age, sex, BMI, CCS, CHA2DS2-VASc score, family history of AF, prior AF hospitalization, history of A Flutter, diabetes, NYHA class, and proportion with sleep apnea, heart disease, CAD, CHF, or EF >35%. Four-year Kaplan-Meier event rates showed considerable differences in treatment effects between NA and non-NA patients (see Table). Ablation was associated with a 50% reduction in the primary endpoint in non-NA (HR 0.50, 95% CI 0.24 to 1.03) vs a 5% reduction in NA (HR 0.95, 95% CI 0.69 to 1.30) enrollees despite higher event rates in NA patients. The trend of favorable outcome with ablation at non-NA sites was maintained after adjustment for baseline covariates that differed between the non-NA (HR 0.51, 95% CI 0.24 to 1.04) and NA populations (HR 0.93, 95% CI 0.68 to 1.20). Conclusion We observed substantial geographic variation in clinical outcomes and treatment effects in the CABANA trial that suggests an important disconnection between overall event rates and treatment benefit from ablation in AF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIH

Background: Inability to eliminate intramural arrhythmogenic substrate may lead to recurrent ventricular tachycardia after catheter ablation. The aim of the present study was to evaluate intramural and full thickness lesion formation using a heated saline-enhanced radiofrequency (SERF) needle-tip catheter, compared with a conventional ablation catheter in normal and infarcted myocardium. Methods: Twenty-two adult mongrel dogs (30–40 kg, 15 normal and 7 myocardial infarct group) were studied. Lesions were created using the SERF catheter (40 W/50 °C) or a standard contact force (CF) catheter in both groups. Results: Comparing SERF to CF ablation, the SERF catheter produced larger lesion volumes than the standard CF catheter—even with >20 g of CF—in both normal (983.1±905.8 versus 461.9±178.3 mm 3 ; P =0.023) and infarcted left ventricular myocardium (1052.3±543.0 versus 340.3±160.5 mm 3 ; P =0.001). SERF catheter lesions were more often transmural than standard CF lesions with >20 g of CF in both groups (59.1% versus 7.7%; P <0.001 and 60.0% versus 12.5%; P =0.017, respectively). Using the SERF catheter, mean depth of ablated lesions reached 90% of the left ventricular wall in both normal and infarcted myocardium. Conclusions: The SERF catheter created more transmural and larger ablative lesions in both normal and infarcted canine myocardium. SERF ablation is a promising new approach for endocardial intramural and full thickness ablation of ventricular tachycardia substrate that is not accessible with current techniques.

Background: Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods: Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. Results: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. Conclusions: Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

Background: Pulmonary vein (PV) stenosis is a highly morbid condition that can result after catheter ablation for PV isolation. We hypothesized that pulsed field ablation (PFA) would reduce PV stenosis risk and collateral injury compared with irrigated radiofrequency ablation (IRF). Methods: IRF and PFA deliveries were randomized in 8 dogs with 2 superior PVs ablated using one technology and 2 inferior PVs ablated using the other technology. IRF energy (25–30 W) or PFA was delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography scans were collected at 0, 2, 4, 8, and 12-week (termination) time points to monitor PV cross-sectional area at each PV ablation site. Results: Maximum average change in normalized cross-sectional area at 4-weeks was −46.1±45.1% post-IRF compared with −5.5±20.5% for PFA ( P ≤0.001). PFA-treated targets showed significantly fewer vessel restrictions compared with IRF ( P ≤0.023). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites, compared with more confined and often incomplete lesions after IRF. At the distal PV sites, only IRF ablations were grossly identified based on focal fibrosis. Mild chronic parenchymal hemorrhage was noted in 3 left superior PV lobes after IRF. Damage to vagus nerves as well as evidence of esophagus dilation occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. Conclusions: PFA significantly reduced risk of PV stenosis compared with IRF postprocedure in a canine model. IRF also caused vagus nerve, esophageal, and lung injury while PFA did not.

Background: The optimal timing of catheter ablation for atrial fibrillation (AF) in reference to the time of diagnosis is unknown. We sought to assess the impact of the duration between first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), on AF recurrence following catheter ablation. Methods: We conducted a systematic electronic search for observational studies reporting the outcomes associated with catheter ablation for atrial fibrillation stratified by diagnosis-to-ablation time. The primary meta-analysis using a random effects model assessed AF recurrence stratified by DAT ≤1 year versus >1 year. A secondary analysis assessed outcomes stratified by DAT ≤3 years versus >3 years. Results: Of the 632 screened studies, 6 studies met inclusion criteria for a total of 4950 participants undergoing AF ablation for symptomatic AF. A shorter DAT ≤1 year was associated with a lower relative risk of AF recurrence compared with DAT >1 year (relative risk, 0.73 [95% CI, 0.65–0.82]; P <0.001). Heterogeneity was moderate (I 2 =51%). When excluding the one study consisting of only patients with persistent AF, the heterogeneity improved substantially (I 2 =0%, Cochran’s Q P =0.55) with a similar estimate of effect (relative risk, 0.78 [95% CI, 0.71–0.85]; P <0.001). Conclusions: Shorter duration between time of first AF diagnosis and AF ablation is associated with an increased likelihood of ablation procedural success. Additional study is required to confirm these results and to explore implementation of earlier catheter AF ablation and patient outcomes within the current AF care pathway. Visual Overview A visual overview is available for this article.

Abstract Objectives The aim of this study was to describe management of recurrent pulmonary vein stenosis (PVS) and determine if stenting is superior to balloon angioplasty (BA) in preventing subsequent restenosis. Background PVS is a serious complication of atrial fibrillation ablation. BA and stenting are effective therapies; however, restenosis frequently occurs. Here we report management of recurrent stenosis. Methods This was a prospective observational study performed from 2000 to 2014. Results One hundred and thirteen patients with severe PVS underwent intervention in 88 veins treated with BA and 81 treated with stenting. Forty‐two patients experienced restenosis. Restenosis was more common in veins treated with BA (RRR 53% [95% CI 32–70%, p = .008]). A second intervention was performed in 41 patients. In the 34 vessels treated with initial BA, 24 were treated for restenosis with a stent and 10 were treated with a second BA. The recurrence rate was 46% in those treated with BA followed by stenting and 50% in those treated with two BA procedures. In the 22 veins treated with initial stenting, 9 were treated with another stent and 13 were treated with BA. The recurrence rate was 44% in those treated with a second stent and 46% for those treated with a stent followed by BA. The risk of a third stenosis was the same among all groups (Analysis of variance [ANOVA] p = .99). Limited sample size precluded analysis of outcome by stent size. Conclusions Restenosis occurred in 44% of patients overall. Management is challenging; stenting does not appear to be superior to BA.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

Background: Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited. Methods: Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated. Results: A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, P =0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8–25.6) mm (median and [first–third] quartile). Distances were not significantly different across cardiac chambers. Conclusions: The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.

Abstract 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) <0.001 White 766 (93.9%) 1259 (91.0%) 0.015 CAD 92 (11.2%) 332 (24.0%) <0.001 NYHA ≥II 345 (42.4%) 433 (31.5%) <0.001 Sleep apnea 136 (16.6%) 372 (26.9%) <0.001 CHA2DS2-VASc: Median (Q1, Q3) 3 (3, 4) 2 (1, 3) <0.001 Paroxysmal AF 406 (49.6%) 540 (39.0%) <0.001 Persistent AF 412 (50.4%) 845 (61.0%) AF Hospitalization 353 (43.2%) 521 (37.7%) 0.011 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