Sandeep Panikker

Efficacy of Catheter Ablation for Persistent Atrial Fibrillation A Systematic Review and Meta-Analysis of Evidence From Randomized and Nonrandomized Controlled Trials

Background—Catheter ablation (CA) is commonly performed for persistent atrial fibrillation, but few high-quality randomized controlled trials (RCTs) exist, leading to funding restrictions being proposed in several countries. We performed a random-effects meta-analysis of RCTs and non-RCTs to assess the efficacy of CA for persistent atrial fibrillation. Methods and Results—We systematically searched PubMed, EMBASE, CENTRAL, OpenGrey, and clinicaltrials.gov for RCTs and non-RCTs reporting clinical outcomes after CA for persistent atrial fibrillation. Forty-six eligible studies were identified containing 3819 patients. After a single procedure, CA significantly reduced the risk of recurrent atrial fibrillation compared with medical therapy (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.20–0.53; P<0.001). Outcomes were better if the pulmonary veins were encircled (OR, 0.26; 95% CI, 0.09–0.74; P=0.01), and electrical isolation reduced AF recurrence compared with purely anatomic encirclement (OR, 0.33; 95% CI, 0.13–0.86; P=0.02). Linear ablation within the left atrium (OR, 0.22; 95% CI, 0.10–0.49; P<0.001), but not complex fractionated atrial electrogram ablation (OR, 0.64; 95% CI, 0.35–1.18; P=0.15), significantly reduced AF recurrence. Results were not improved by performing more extensive linear lesion sets (OR, 0.77; 95% CI, 0.41–1.43; P=0.40) or from biatrial ablation (OR, 0.62; 95% CI, 0.31–1.24; P=0.17). Where data were available, the relative benefits seen held true both after a single or multiple procedure(s). Sensitivity analyses showed that inclusion of non-RCTs increased statistical power without biasing the calculated effect sizes. Conclusions—For patients with persistent atrial fibrillation, CA achieves significantly greater freedom from recurrent atrial fibrillation compared with medical therapy. The most efficacious strategy is likely to combine isolation of the pulmonary veins with limited linear ablation within the left atrium.Background— Catheter ablation (CA) is commonly performed for persistent atrial fibrillation, but few high-quality randomized controlled trials (RCTs) exist, leading to funding restrictions being proposed in several countries. We performed a random-effects meta-analysis of RCTs and non-RCTs to assess the efficacy of CA for persistent atrial fibrillation. Methods and Results— We systematically searched PubMed, EMBASE, CENTRAL, OpenGrey, and [clinicaltrials.gov][1] for RCTs and non-RCTs reporting clinical outcomes after CA for persistent atrial fibrillation. Forty-six eligible studies were identified containing 3819 patients. After a single procedure, CA significantly reduced the risk of recurrent atrial fibrillation compared with medical therapy (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.20–0.53; P <0.001). Outcomes were better if the pulmonary veins were encircled (OR, 0.26; 95% CI, 0.09–0.74; P =0.01), and electrical isolation reduced AF recurrence compared with purely anatomic encirclement (OR, 0.33; 95% CI, 0.13–0.86; P =0.02). Linear ablation within the left atrium (OR, 0.22; 95% CI, 0.10–0.49; P <0.001), but not complex fractionated atrial electrogram ablation (OR, 0.64; 95% CI, 0.35–1.18; P =0.15), significantly reduced AF recurrence. Results were not improved by performing more extensive linear lesion sets (OR, 0.77; 95% CI, 0.41–1.43; P =0.40) or from biatrial ablation (OR, 0.62; 95% CI, 0.31–1.24; P =0.17). Where data were available, the relative benefits seen held true both after a single or multiple procedure(s). Sensitivity analyses showed that inclusion of non-RCTs increased statistical power without biasing the calculated effect sizes. Conclusions— For patients with persistent atrial fibrillation, CA achieves significantly greater freedom from recurrent atrial fibrillation compared with medical therapy. The most efficacious strategy is likely to combine isolation of the pulmonary veins with limited linear ablation within the left atrium. [1]: http://clinicaltrials.gov

Relationship between contact force sensing technology and medium-term outcome of atrial fibrillation ablation: a multicenter study of 600 patients.

Contact force sensing (CFS) technology improves acute pulmonary vein isolation durability; however, its impact on the clinical outcome of ablating atrial fibrillation (AF) is unknown.

Left Atrial Appendage Electrical Isolation and Concomitant Device Occlusion to Treat Persistent Atrial Fibrillation: A First-in-Human Safety, Feasibility, and Efficacy Study.

Background—Left atrial appendage (LAA) electric isolation is reported to improve persistent atrial fibrillation (AF) ablation outcomes. However, loss of LAA mechanical function may increase thromboembolic risk. Concomitant LAA electric isolation and occlusion as part of conventional AF ablation has never been tested in humans. We therefore evaluated the feasibility, safety, and efficacy of LAA electric isolation and occlusion in patients undergoing long-standing persistent AF ablation. Methods and Results—Patients with long-standing persistent AF (age, 68±7 years; left atrium diameter, 46±3 mm; and AF duration, 25±15 months) underwent AF ablation, LAA electric isolation, and occlusion. Outcomes were compared with a balanced (1:2 ratio) control group who had AF ablation alone. Among 22 patients who underwent ablation, LAA electric isolation was possible in 20. Intraprocedural LAA reconnection occurred in 17 of 20 (85%) patients, predominantly at anterior and superior locations. All were reisolated. LAA occlusion was successful in all 20 patients. There were no major periprocedural complications. Imaging at 45 days and 9 months confirmed satisfactory device position and excluded pericardial effusion. One of twenty (5%) patients had a gap of ≥5 mm requiring anticoagulation. Nineteen of twenty (95%) patients stopped warfarin at 3 months. Without antiarrhythmic drugs, freedom from AF at 12 months after a single procedure was significantly higher in the study group (19/20, 95%) than in the control group (25/40, 63%), P=0.036. Freedom from atrial arrhythmias was demonstrated in 12 of 20 (60%) and 18 of 20 (90%) patients after 1 and ⩽2 procedures (mean, 1.3), respectively. Conclusions—Persistent AF ablation, LAA electric isolation, and mechanical occlusion can be performed concomitantly. This technique may improve the success of persistent AF ablation while obviating the need for chronic anticoagulation. Clinical Trial Registration—URL: https://clinicaltrials.gov. Unique identifier: NCT02028130.

CT imaging for left atrial appendage closure: a review and pictorial essay.

Cardioembolic stroke is an important complication of atrial fibrillation. The thrombus responsible for this arises from the left atrial appendage (LAA) in >90% of cases, providing the rationale for device-based LAA closure as a means of thromboprophylaxis. Although oral anticoagulant therapy remains the mainstay for reducing the risk of stroke in patients with atrial fibrillation, an increasing number of patients, particularly those ineligible for conventional pharmacotherapy, are being offered percutaneous left atrial appendage closure. Cardiovascular CT can provide important information to assess the suitability of patients for LAA interventions and guide device selection and approach. The high spatial resolution and multiplanar capability of contemporary contrast-enhanced gated multidetector cardiovascular CT render it an ideal modality for noninvasively evaluating patients before intervention and assessing patients after intervention both for complications and procedural outcome.

Biatrial linear ablation in sustained nonpermanent AF: Results of the substrate modification with ablation and antiarrhythmic drugs in nonpermanent atrial fibrillation (SMAN-PAF) trial

BACKGROUND More advanced atrial fibrillation (AF) is associated with lower success rates after pulmonary vein isolation (PVI), and the optimal ablation strategy is uncertain. OBJECTIVES To assess the impact of additional linear ablation (lines) compared to PVI alone. METHODS In this multicenter randomized controlled trial, 122 patients (mean age 61.9 ± 10.5 years; left atrial diameter 43 ± 6 mm) with persistent AF (PeAF) or sustained (>12 hours) paroxysmal AF (SusPAF) with risk factors for atrial substrate were included and followed up for 12 months. Patients were randomized to PVI-only or PVI + lines (left atrial roof line, mitral isthmus line, and tricuspid isthmus line) group. Holter monitoring was performed at 3, 6, and 12 months and according to symptoms. The primary outcome was atrial tachyarrhythmia recurrence lasting ≥30 seconds. RESULTS Baseline characteristics were comparable between groups; 61% had PeAF and 39% SusPAF. Successful PVI was achieved for 98% of pulmonary veins, and bidirectional block was obtained in 90% of lines. The primary end point occurred in 38% of the PVI + lines group and 32% of the PVI-only group (P = .50), which was consistent in both PeAF (36% vs 28%; P = .45) and SusPAF (42% vs 39%; P = .86). Compared with the PVI-only group, the PVI + lines group had higher procedure duration (209 ± 52 minutes vs 172 ± 44 minutes; P < .001), ablation time (4352 ± 1084 seconds vs 2503 ± 1061 seconds; P < .001), and radiation exposure (Dose-area product 3992 ± 6496 Gy·cm(2) vs 2106 ± 1679 Gy·cm(2); P = .03). Quality of life (disease-specific Atrial Fibrillation Effect on Quality of Life questionnaire and mental component scale of the Short Form 36 Health Survey) improved significantly during the study but did not differ between groups. CONCLUSION Adding lines to wide antral PVI in substrate-based AF requires significantly more ablation, increases procedure duration and radiation dose, but provides no additional clinical benefit.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation

AIMS The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. METHODS AND RESULTS Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). CONCLUSION Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation.

Left atrial appendage electrical isolation and concomitant device occlusion: A safety and feasibility study with histologic characterization

BACKGROUND Left atrial appendage (LAA) electrical isolation is reported to improve atrial fibrillation ablation outcomes. However, loss of mechanical function may increase thromboembolic risk. OBJECTIVE The aim of this study was to evaluate the feasibility and safety of LAA occlusion after electrical isolation in a canine model. METHODS Nine canines underwent LAA isolation with irrigated radiofrequency ablation after pulmonary vein (PV) isolation. Entrance and exit block were confirmed with intravenous adenosine after 30 minutes. The LAA was then occluded with a Watchman device. Device position was assessed at 10 days by using transthoracic echocardiography. At 45 days, LAA isolation was assessed epicardially. Hearts were then examined macroscopically and histologically. RESULTS All 36 PVs and 8 of 9 LAAs (89%) were electrically isolated. Acute LAA reconnection occurred in 4 of 8 LAAs (50%). All were reisolated. The mean ablation time was 51 ± 19 minutes, including 24 ± 18 minutes for LAA isolation. LAA occlusion was successful in all cases. One animal died of a primary intracranial bleed due to anticoagulant hypersensitivity 36 hours after the procedure. Transthoracic echocardiography at 10 days confirmed satisfactory device positions and no pericardial effusion. At 45 days, 7 of 8 (88%) had persistent LAA electrical isolation. All devices were stable without evidence of erosion. Microscopy revealed complete device-tissue apposition and a mature connective tissue layer overlying the device surface in all cases. CONCLUSION LAA electrical isolation and mechanical occlusion can be performed concomitantly in this animal model, with no displacement or mechanical erosion of the appendage at 45 days. This technique can potentially improve success rates and obviate the need for chronic anticoagulation. Future studies should address efficacy, safety, and feasibility in humans.

Evaluation of a novel high-resolution mapping system for catheter ablation of ventricular arrhythmias.

BACKGROUND The mapping of ventricular arrhythmias in humans using a minibasket 64-electrode catheter paired with a novel automatic mapping system (Rhythmia) has not been evaluated. OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of mapping ventricular arrhythmias and clinical outcomes after ablation using this system. METHODS Electroanatomic maps for ventricular arrhythmias were obtained during 20 consecutive procedures in 19 patients (12 with ventricular tachycardia [VT] and 2 with ventricular ectopy [VE]). High-density maps were acquired using automatic beat acceptance and automatic system annotation of electrograms. RESULTS Forty-seven electroanatomic maps (including 3 right ventricular and 9 epicardial maps) were obtained. Left ventricular endocardial mapping by transseptal (n = 13) and/or transaortic (n = 11) access was safe with no complications related to the minibasket catheter. VT substrate maps (n = 14; median 10,184 points) consistently demonstrated late potentials with high resolution. VT activation maps (n = 25; median 6401 points) obtained by automatic annotation included 7 complete maps (covering ≥90% of the tachycardia cycle length) in 5 patients in whom the entire VT circuit was accurately visualized. VE timing maps (n = 8) successfully localized the origin of VEs in all, with all accepted beats consistent with clinical VEs. Over a median follow-up of 10 months, no arrhythmia recurrence was noted in 75% after VT ablation and 86% after VE ablation. CONCLUSION In this first human experience for ventricular arrhythmias using this system, ultra-high-density maps were created rapidly and safely, with a reliable automatic annotation of VT and consistent recording of abnormal electrograms. Medium-term outcomes after ablation were encouraging. Further larger studies are needed to validate these findings.

Catheter ablation vs electrophysiologically guided thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: The CASA-AF Study

BACKGROUND Catheter ablation (CA) outcomes for long-standing persistent atrial fibrillation (LSPAF) remain suboptimal. Thoracoscopic surgical ablation (SA) provides an alternative approach in this difficult to treat cohort. OBJECTIVE To compare electrophysiological (EP) guided thoracoscopic SA with percutaneous CA as the first-line strategy in the treatment of LSPAF. METHODS Fifty-one patients with de novo symptomatic LSPAF were recruited. Twenty-six patients underwent electrophysiologically guided thoracoscopic SA. Conduction block was tested for all lesions intraoperatively by an independent electrophysiologist. In the CA group, 25 consecutive patients underwent stepwise left atrial (LA) ablation. The primary end point was single-procedure freedom from atrial fibrillation (AF) and atrial tachycardia (AT) lasting >30 seconds without antiarrhythmic drugs at 12 months. RESULTS Single- and multiprocedure freedom from AF/AT was higher in the SA group than in the CA group: 19 of 26 patients (73%) vs 8 of 25 patients (32%) (P = .003) and 20 of 26 patients (77%) vs 15 of 25 patients (60%) (P = .19), respectively. Testing of the SA lesion set by an electrophysiologist increased the success rate in achieving acute conduction block by 19%. In the SA group, complications were experienced by 7 of 26 patients (27%) vs 2 of 25 patients (8%) in the CA group (P = .07). CONCLUSION In LSPAF, meticulous electrophysiologically guided thoracoscopic SA as a first-line strategy may provide excellent single-procedure success rates as compared with those of CA, but there is an increased up-front risk of nonfatal complications.

Cardiac CT assessment of tissue thickness at the ostium of the left atrial appendage predicts acute success of radiofrequency ablation

Tissue thickness at the site of ablation is a determinant of lesion transmurality. We reported the feasibility, safety, and efficacy of longstanding persistent atrial fibrillation ablation, incorporating deliberate left atrial appendage (LAA) isolation and occlusion, and identified systematic differences in ostial LAA tissue thickness in a matched cohort of cadaveric specimens.