Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

Perioperative Safety and Early Patient and Device Outcomes Among Subcutaneous Versus Transvenous Implantable Cardioverter Defibrillator Implantations : A Randomized, Multicenter Trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. OBJECTIVE: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). DESIGN: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255). SETTING: The ATLAS trial. PATIENTS: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). MEASUREMENTS: The primary outcome was perioperative major lead-related complications. RESULTS: There was a statistically significant reduction in perioperative, lead-related complications, which occurred in 1 patient (0.4%) with an S-ICD and in 12 patients (4.8%) with TV-ICD (-4.4%; 95% CI, -6.9 to -1.9; P = 0.001). There was a trend for more inappropriate shocks with the S-ICD (hazard ratio [HR], 2.37; 95% CI, 0.98 to 5.77), but no increase in failed appropriate ICD shocks (HR, 0.61 (0.15 to 2.57). Patients in the S-ICD group had more ICD site pain, measured on a 10-point numeric rating scale, on the day of implant (4.2 ± 2.8 vs. 2.9 ± 2.2; P < 0.001) and 1 month later (1.3 ± 1.8 vs. 0.9 ± 1.5; P = 0.035). LIMITATION: At present, the ATLAS trial is underpowered to detect differences in clinical shock outcomes; however, extended follow-up is ongoing. CONCLUSION: The S-ICD reduces perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. PRIMARY FUNDING SOURCE: Boston Scientific.

Left bundle branch area pacing in patients with atrioventricular conduction disease: A prospective multicenter study.

BACKGROUND: The reported success rate of His-bundle pacing (HBP) in patients with infranodal atrioventricular (AV) conduction disease is only 52%-76%. The success rate of left bundle branch area pacing (LBBAP) in this cohort is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility, safety, and electrophysiological characteristics of LBBAP in patients with AV conduction disease. METHODS: Patients with AV conduction disease referred for pacemaker implantation at 2 centers between February 2019 and June 2021 were considered for LBBAP. Baseline demographic characteristics, procedural success rates, electrophysiological parameters, and complications were assessed. RESULTS: LBBAP was successful in 340 of 364 patients (93%). Mean age was 72 ± 13 years, and mean follow-up was 331 ± 244 days. Pacing indications were Mobitz I in 27 patients (7%), Mobitz II or 2:1 AV block or high-grade AV block in 94 patients (26%), complete heart block in 199 patients (55%), and sick sinus syndrome with isolated bundle branch block in 44 patients (12%). Left bundle branch block and right bundle branch block were present in 57 patients (16%) and 140 patients (38%), respectively. Procedural success rates did not differ between indications (92.6%, 93.6%, 92.9%, and 95%, respectively) or between patients with narrow (<120 ms) vs wide QRS (≥120 ms). Mean LBBAP threshold was 0.77 ± 0.34 V at 0.4 ms at implant and remained stable during follow-up. There were 4 (1.2%) acute LBBAP lead dislodgments. CONCLUSION: LBBAP is safe and feasible with high success rates for patients with AV conduction disease. In contrast to HBP, LBBAP success rates remain high over the entire spectrum of AV conduction disease, and lead parameters remain stable during follow-up.

Fluoroless Catheter Ablation of Atrial Fibrillation: Integration of Intracardiac Echocardiography and Cartosound Module.

OBJECTIVE: To evaluate the feasibility, safety, and clinical efficacy of non-fluoroscopic radiofrequency catheter ablation of atrial fibrillation (AF) in comparison to traditional fluoroscopy-guided ablation in a local Canadian community cohort. METHODS: We retrospectively studied consecutive patients with paroxysmal and persistent AF undergoing pulmonary vein isolation (PVI) guided by intracardiac echocardiography (ICE) and Carto system (CartoSound module). ICE-guided PVI without fluoroscopy (Zero-fluoro group) was performed in 116 patients, and conventional fluoroscopy-guided PVI (Traditional group) was performed in 131 patients. RESULTS: Two hundred and forty-seven patients with AF (60.7% male; mean age: 62.2 ± 10.6 years; paroxysmal AF =63.1%) who underwent PVI were studied. Mean procedure times were similar between both groups (136.8±33.4 minutes in the zero-fluoro group vs. 144.3±44.9 minutes in the traditional group; p=0.2). Acute PVI was achieved in all patients. Survival from early AF recurrence was 85% and 81% in the zero-fluoro and traditional groups, respectively (p = 0.06). Survival from late AF recurrence (12-months) between the zero-fluoro and traditional groups was also similar (p=0.1). Moreover, there were no significant differences between complication rates, including hematoma (p = 0.2) and tamponade (p = 1),between both groups. CONCLUSIONS: Zero-fluoroscopy ICE and CartoSound-guided AF ablation may be safe and feasible in patients undergoing PVI compared to conventional fluoroscopy-guided ablation.

Safety and feasibility of left bundle branch area pacing following valvular interventions: Multicenter study.

OBJECTIVES: To evaluate the safety and feasibility of left bundle branch area pacing (LBBAP) in patients with valvular interventions. METHODS: Eighty-four patients were included in this study. All patients underwent recent surgical or percutaneous valvular interventions. LBBAP was attempted in all patients. Implant success rates, peri- and postprocedure electrocardiogram, pacing parameters, and complications were assessed at implant, and during follow-up. RESULTS: LBBAP implantation was successful in 80/84 (95%) patients. Mean age was 74.1 ± 13.8 years and 56% patients were male. Prior valvular replacements included: percutaneous aortic (26), surgical aortic (36), combined surgical aortic plus mitral (6), MVR (10), tricuspid (1), and pulmonic (1). Average LVEF was 52.6 ± 11%. Majority of patients underwent LBBAP due to atrioventricular block (76%) and sinus node disease (13%). Total procedure duration was 74.1 ± 12.5 min and fluoroscopic duration was 9.7 ± 6.8 min. Pacing parameters were stable during follow-up period of 10.0 ± 6.3 months. Pacing QRS duration was significantly narrower than baseline QRS duration (131.5 ± 31.4 ms vs. 114.3 ± 13.7 ms, p < .001, respectively). No acute complications were observed. Mean follow-up was 10.0 ± 6.3 months (median: 8.4 months, min: 1 and max: 24 months). During follow-up, there were three device infections and two patients had loss of LBBA capture within 1 month of implant. CONCLUSIONS: LBBAP is a feasible and safe pacing modality in patients with prior interventions for valvular heart disease.

Initial Experience, Safety, and Feasibility of Left Bundle Branch Area Pacing: A Multicenter Prospective Study.

OBJECTIVES: This study sought to evaluate the safety and feasibility of conduction system pacing by performing left bundle branch area pacing (LBBAP). BACKGROUND: There are limited data from single centers showing that LBBAP may circumvent the technical and electrophysiological challenges encountered with His bundle pacing. METHODS: Patients referred for pacemaker implantation at 2 centers between February 1, 2019, and March 31, 2020, were considered for LBBAP. LBBAP was performed by implanting a lumen-less, exposed helix lead approximately 2 cm distal to the His bundle and deep into the septum using a specialized delivery sheath. Implant success rates, complications, and electrophysiological parameters were assessed. RESULTS: LBBAP was successful in 305 of 341 patients (89%). Mean age was 72 ± 12 years; 45% were women; and 39% had QRS duration (QRSd) >130 ms, 22% right bundle branch block, 11% left bundle branch block, and 6% intraventricular conduction defect. Pacing indications were sinus node dysfunction in 28.7%, atrioventricular block in 52.5%, cardiac resynchronization therapy in 8.8%, and refractory atrial fibrillation in 10% of patients. Procedural duration was 74.7 ± 34 min and fluoroscopic time was 10.4 ± 8.1 min. The mean baseline QRSd and paced QRSd in the overall cohort was 114 ± 29.8 ms versus 112 ± 11.7 ms (p < 0.001) and in patients with infra-Hisian disease was 144.5 ± 19 ms versus 115 ± 12 ms (p < 0.001), respectively. Mean left ventricular activation time was 71.7 ± 11 ms at high output and 74.7 ± 11 ms at low output. LBB potentials were noted in 41% patients. Pacing threshold and R waves were 0.74 ± 0.3 V at 0.4 ms and 10.7 ± 4.9 mV at time of implantation and were stable at 1-, 3-, 6-, and 12-month follow-ups. The only major complications were 3 LBBAP lead dislodgements, 2 within 24 h and 1 at 2 weeks. CONCLUSIONS: LBBA pacing is safe, feasible, and a reliable alternative to His bundle pacing for providing physiological pacing. Randomized controlled studies are needed to confirm the safety, feasibility, and clinical outcomes of LBBAP.

Rationale and design of the randomized prospective ATLAS study: Avoid Transvenous Leads in Appropriate Subjects.

BACKGROUND: The defibrillator lead is the weakest part of the transvenous (TV) implantable cardioverter defibrillation (ICD) system and a frequent cause of morbidity. Lead dislodgement, cardiac perforation, insertion-related trauma including pneumothorax and vascular injury, are common early complications of TV-ICD implantation. Venous occlusion, tricuspid valve dysfunction, lead fracture and lead insulation failure are additional, later complications. The introduction of a totally sub-cutaneous ICD (S-ICD) may reduce these lead-related issues, patient morbidity, hospitalizations and costs. However, such benefits compared to the TV-ICD have not been demonstrated in a randomized trial. DESIGN: ATLAS (Avoid Transvenous Leads in Appropriate Subjects) is a multi-centered, randomized, open-label, parallel group trial. Patients younger than 60 years are eligible. If older than 60 years, patients are eligible if they have an inherited heart rhythm disease, or risk factors for ICD-related complication, such as hemodialysis, a history of ICD or pacemaker infection, heart valve replacement, or severe pulmonary disease. This study will determine if using an S-ICD compared to a TV-ICD reduces a primary composite outcome of perioperative complications including pulmonary or pericardial perforation, lead dislodgement or dysfunction, tricuspid regurgitation and ipsilateral venous thrombosis. Five hundred patients will be enrolled from 14 Canadian hospitals, and data collected to both early- (at 6 months) and mid-term complications (at 24 months) as well as mortality and ICD shock efficacy. SUMMARY: The ATLAS randomized trial is comparing early- and mid-term vascular and lead-related complications among S-ICD versus TV-ICD recipients who are younger or at higher risk of ICD-related complications.

Prospective evaluation of integrated device diagnostics for heart failure management: results of the TRIAGE-HF study.

AIMS: The primary aim of the TRIAGE-HF trial was to correlate cardiac implantable electronic device-generated heart failure risk status (HFRS) with signs, symptoms, and patient behaviours classically associated with worsening heart failure (HF). METHODS AND RESULTS: TRIAGE-HF enrolled 100 subjects with systolic HF implanted with a Medtronic high-performance device and followed up at three Canadian HF centres. Study follow-up was up to 8 months. The HFRS assigned each subject's overall risk of HF hospitalization in the next 30 days and also highlighted abnormal device parameters contributing to a patient's risk status at the time of remote data transmission. Subjects with a high HFRS were contacted by telephone to assess symptoms, and compliance with prescribed therapies, nutrition, and exercise. Clinician-assessed risk and HFRS-calculated risk were correlated at both study baseline and exit. Twenty-four high HFRS occurrences were observed among 100 subjects. Device parameters associated with increased risk of HF hospitalization included OptiVol index (n = 20), followed by low patient activity (n = 18) and elevated night heart rate (n = 12). High HFRS was associated with symptoms of worsening HF in 63% of cases (n = 15) increasing to 83% of cases (n = 20) when non-compliance with pharmacological therapies and lifestyle was considered. CONCLUSIONS: TRIAGE-HF is the first study to provide prospective data on the distribution of abnormal device parameters contributing to high HFRS. High HFRS has good predictive accuracy for patient-reported signs, symptoms, and behaviours associated with worsening HF status. As such, HFRS may be a useful tool for ambulatory HF monitoring to improve both patient-centred and health system level outcomes.

Risk of Stroke and Recurrence After AF Ablation in Patients With an Initial Event-Free Period of 12 Months.

INTRODUCTION: Because of the unclear prognostic effects of ablation of atrial fibrillation (AF), oral anticoagulation (OAC) is often continued after ablation even in asymptomatic patients. We sought to determine the frequency of stroke and AF recurrence in patients on and off therapeutic OAC 1 year after a successful AF ablation. METHODS AND RESULTS: Patients that underwent AF ablation and were free of AF 12 months after ablation were selected from our AF database. During follow-up (FU), patients were screened for recurrence of AF, changes in OAC or antiarrhythmic medication, and the occurrence of stroke or transient ischemic attack (TIA). A total of 398 patients (median age 60.7 years [50.8, 66.8], 25% female) were investigated. The median duration of FU was 529 (373, 111,3.5) days. OAC was discontinued in 276 patients (69.3%). During FU, 4 patients (1%) suffered from stroke and 55 patients (13.8%) experienced a recurrence of AF. Persistent AF was significantly associated with a greater chance of AF recurrence (49.1% vs. 26.8%; P = 0.001). Neither CHADS2 nor CHA2DS2-VASc-Score nor recurrence of AF were significantly different in patients with or without stroke. There was a trend toward a higher percentage of coronary artery disease among patients that experienced stroke (50% vs. 10%; P = 0.057). CONCLUSION: The overall risk of stroke and AF recurrence is low in patients with a recurrence free interval of at least 12 months after AF ablation. Of note, recurrence of AF was not associated with a higher risk of stroke in our study population.

Predictors for Progression of Atrial Fibrillation in Patients Awaiting Atrial Fibrillation Ablation.

BACKGROUND: Success rates of atrial fibrillation (AF) ablation have been shown to be significantly lower for patients with persistent AF. However, little is known about the risk factors predicting progression to persistent AF in patients awaiting AF ablation. METHODS: We performed a retrospective, single-centre investigation of patients with paroxysmal AF at the time of placement on the ablation waiting list. Patients were defined as having progressed if they had developed self-reported or electrocardiogram-recorded AF durations more than 7 days while awaiting ablation. After ablation, clinical visits at 3, 6, 9, 12, and 18 months were performed with a minimum of a 48-hour-Holter and electrocardiogram. Baseline characteristics including left atrial diameter (LA) and the HATCH score were analyzed by univariable and multivariable analysis for predicting progression to persistent AF. RESULTS: During a median waiting time of 9.7 (6.1, 14.2) months, 60 of 564 patients (11%) progressed to persistent AF. In patients who progressed, ablation took longer (180 [150, 249] minutes vs 157 [125, 210] minutes; P = 0.009) and was associated with a higher rate of recurrence after a median of 12 months (53.3% vs 39.1%; P < 0.001). The HATCH score was a poor predictor of AF progression (area under the curve 0.54), whereas an LA diameter of more than 45 mm (odds ratio 3.46, P < 0.001) and heart failure (odds ratio 3.11, P = 0.036) were strong and independent predictors of AF progression in multivariable analysis. CONCLUSIONS: Patients with an increased LA diameter or heart failure have a significantly increased risk of progression to persistent AF. These characteristics may define patients who should undergo earlier catheter ablation to optimize outcome.

The Impact of Duration of Atrial Fibrillation Recurrences on Measures of Health-Related Quality of Life and Symptoms.

BACKGROUND: Little is known about the relationship between daily atrial fibrillation (AF) burden and quality of life (QOL). We sought to determine the influence of atrial tachycardia (AT) or AF burden on measures of QOL and symptoms. METHODS AND RESULTS: We retrospectively analyzed patients with dual-chamber pacemakers from the Atrial Septal Pacing Efficacy Clinical Trial (ASPECT), Atrial Therapy Efficacy and Safety Trial (ATTEST), and aTRial arrhythmias dEtected by implaNted Device diagnostics Study (TRENDS) trials. All patients underwent at least one QOL evaluation. We predefined four AF burden groups: no AT/AF (group 1), ≤30 minutes (group 2), 30 minutes-2 hours (group 3), and >2 hours (group 4) per day. We compared QOL measures using the 12-item Short-Form Health Survey (SF-12; standard 4 week recall) and the AF Symptom Checklist (SC) severity and frequency between groups 2-4 to those in group 1. A total of 798 patients were analyzed (age 72 ± 11 years, 447 male [56%]). SC frequency and severity and SF-12 physical and mental scores worsened significantly when patients in group 4 were compared to patients with no AF. There were no statistically significant differences for any of the measures when comparing group 2 or 3 patients to group 1. By linear regression, only the 2-hour-cutoff had a significant impact on QOL as measured by SC frequency (+3.15, P < 0.001), severity (+3.23, P < 0.001), SF-12 physical score (-2.42, P = 0.013), and SF-12 mental score (-2.11, P = 0.021). CONCLUSION: A daily AT/AF burden of more than 2 hours had significant impact on QOL. This might influence the choice of appropriate cut-off points to determine the success of an AF treatment.

Substrate-guided ablation of haemodynamically tolerated and untolerated ventricular tachycardia in patients with structural heart disease: effect of cardiomyopathy type and acute success on long-term outcome.

AIMS: The purpose of this study was to evaluate the outcomes of purely substrate-guided ventricular tachycardia (VT) ablation in patients with non-ischaemic dilated cardiomyopathy (NIDCM) and ischaemic cardiomyopathy (ICM) and the impact of acute procedural success on long-term outcome. METHODS AND RESULTS: One hundred and forty-two patients (65 ± 12 years old, 72% male) with ICM (n = 87) and with NIDCM (n = 55) underwent substrate-guided VT ablation. The ablation approach involved eliminating all LP regions and ablating all scar border zone regions with 10 or more out of 12 pace-matching. All patients were followed with regular implantable defibrillator interrogations for mean 641 ± 301 days. Complete acute success (no inducible VT) was achieved in 60 patients with ICM (69%) and in 29 patients with NIDCM (53%) (P = 0.03). Partial success (elimination of clinical VT only) was obtained in nine patients with ICM (10%) and in four patients with NIDCM (7%) (P = 0.14). Procedural failure (clinical VT still inducible) occurred in 18 patients within the ICM group (21%) and in 22 patients of the NIDCM (40%) (P = 0.04). Overall, 51 patients presented with recurrence of ventricular arrhythmias: 23 in the group with ICM (26%) and 28 in the group with NIDCM (51%) (P = 0.03). Long-term success was related to acute procedural outcome. CONCLUSIONS: Substrate-guided ablation is an effective approach in the treatment of VT with long-term outcome directly related to acute procedural success. Success rates are significantly lower in patients with NIDCM compared with those with ICM.

Comparison of outcomes after cardioversion or atrial fibrillation ablation in patients with differing periprocedural anticoagulation regimens.

BACKGROUND: There is a paucity of data that compare traditional vitamin K antagonist (VKA) with novel oral anticoagulant regimens in periprocedural management of cardioversion or ablation of atrial fibrillation (AF). We sought to compare outcomes of use of VKA, dabigatran (DABI), and rivaroxaban (RIVA) anticoagulation around the time of intervention. METHODS: We studied consecutive patients undergoing cardioversion or ablation of AF at our centre from October 2010 to October 2013. There were 3 different anticoagulation groups: warfarin (VKA), DABI, and RIVA. Safety was assessed according to number of strokes, transient ischemic attacks (TIAs), and clinically important and not important bleeding events. RESULTS: Baseline characteristics were well balanced between the groups. Average follow-up was 6 months (± 4 months). A total of 901 patients who underwent cardioversion were studied (VKA [n = 471], DABI [n = 288] and RIVA [n = 141]). In these patients there were no strokes seen during follow-up and 2 TIAs in the DABI group. Bleeding rates were low, with no significant difference between the 3 groups. A total of 680 patients who underwent ablation were studied (VKA [n = 319], DABI [n = 220] and RIVA [n = 171]). There were no strokes reported during follow-up and 3 TIAs: 2 in the VKA group and 1 in the DABI group not resulting in a significant difference between the groups. Bleeding rates were low, with no significant difference between the groups. CONCLUSIONS: Overall, there was a low incidence of adverse events for all anticoagulation regimens. Warfarin, DABI, and RIVA use around the time of the procedure are safe and reasonable options for patients who undergo cardioversion or AF ablation.

Point-by-point pulmonary vein antrum isolation guided by intracardiac echocardiography and 3D mapping and duty-cycled multipolar AF ablation: effect of multipolar ablation on procedure duration and fluoroscopy time.

PURPOSE: Pulmonary vein antrum isolation (PVAI) guided by intracardiac echocardiography and a roaming circular mapping catheter is an effective treatment modality for atrial fibrillation. Unfortunately, the complexity of this technique leads to long procedure times and high fluoroscopy exposure. Single-catheter multipolar ablation holds the promise to reduce these parameters. This study examined the effect of the conventional point-by-point PVAI with that of single-catheter multipolar ablation on the procedural characteristics and clinical outcomes of atrial fibrillation ablation. METHODS: Referred patients underwent PVAI guided by a magnetic-based 3D mapping (CARTO 3(®) System; group 1) or duty-cycled multipolar AF ablation using the pulmonary vein ablation catheter (PVAC, group 2) between June 2010 and May 2011. RESULTS: Data were analyzed from 19 patients in group 1 and 31 patients in group 2. There was no significant difference in the length of the procedure between the two groups (135 ± 26 vs 125 ± 25 min, P = 0.20). Patients who underwent ablation using PVAC spent significantly less time in the procedure room pre- and post-procedure than those who underwent conventional PVAI (205 ± 38 vs 179 ± 30 min, P = 0.02) and had a significantly shorter fluoroscopy exposure (50 ± 16 vs 36 ± 14 min, P = 0.003) and radiofrequency energy delivery time (54 ± 26 vs 32 ± 33 min, P = 0.02). No differences in safety and efficacy were seen between the groups. CONCLUSIONS: Single-catheter multipolar AF ablation was associated with significantly lower fluoroscopy duration, radiofrequency energy delivery time, and the time the patient spent in the procedure room before and after ablation, although measured short-term clinical outcomes were similar.

The use of anticoagulation during the periprocedure period of atrial fibrillation ablation.

PURPOSE OF REVIEW: Ablation is a treatment option for selected patients with atrial fibrillation that is being used more frequently, increasing the importance of awareness of both its risks and benefits. This review discusses the thromboembolic and bleeding risks during ablation, strategies to minimize these risks and use of long-term oral anticoagulation post ablation. RECENT FINDINGS: Thromboembolic and bleeding risks imparted by atrial fibrillation ablation can be minimized by echocardiography, optimal intraprocedural anticoagulation, and use of irrigated catheters and access sheaths with constant heparinized saline flow. Additionally, a strategic approach to periprocedural anticoagulation that may include continuation of warfarin, bridging with low-molecular-weight heparin (LMWH), or use of aspirin alone is essential in the balance of thrombotic and hemorrhagic risks. Novel anticoagulants (direct thrombin inhibitors or anti-Xa inhibitors) may add further options. SUMMARY: The use of atrial fibrillation ablation has increased over the past decade. Along with technique and technology advances that have improved the success of ablation, strides have been made in minimizing thromboembolic and bleeding risks and in the availability of a broader choice of anticoagulants. Research is ongoing to identify patients most suitable for ablation and to determine the long-term efficacy and safety of this treatment option.

Relationship between complex fractionated electrograms (CFE) and dominant frequency (DF) sites and prospective assessment of adding DF-guided ablation to pulmonary vein isolation in persistent atrial fibrillation (AF).

BACKGROUND: Sites of high DF are potential targets for AF ablation, but it is unknown if addition of DF ablation can improve procedural outcome. OBJECTIVES: We sought to (1) examine the relationship between DF sites and complex fractionated electrograms (CFE) and (2) prospectively assess the long-term outcome of adding DF ablation to pulmonary vein antral isolation (PVAI) for persistent AF. METHODS: First, 20 patients with persistent AF who underwent previous CFE-guided ablation and who had AF terminate during ablation were studied retrospectively (group I). Bipolar, 8-second electrograms were collected by a circular catheter (288 ± 86 points/map). The EnSite NavX system allows for automated display of both CFE and DF maps. Electrograms with cycle length <120 ms were considered CFE and were compared to DF sites > 8 Hz (direct inverse relationship). Sites of AF termination were related to CFE and DF sites. Based on these observations, 30 different patients (group II) with persistent AF prospectively underwent DF-guided ablation plus PVAI. They were followed every 3 months for 1 year (visit, Holter, ECG). These patients were compared to case-matched controls undergoing PVAI alone (group III). RESULTS: In group I, there was a significant, inverse correlation between DF and CFE values at each point (r =-0.24, P < 0.001). DF surface area was less than CFE area (27 ± 5 cm(2) vs 34 ± 4 cm(2) , P = 0.03). CFE sites overlapped 48 ± 27% with the DF surface area. Nonoverlapping CFE sites were contiguous to DF sites. AF termination occurred where DF and CFE overlapped, and at these sites, DF was always greater than the mean DF for the map. In group II, all DF sites above the mean value were prospectively ablated during AF. AF termination was noted in only 2/30 (7%) patients. After DF ablation, PVAI was performed and termination increased to 4/30 patients (14%). At 1 year, freedom from atrial arrhythmia > 30 seconds occurred in 57% of DF+PVAI compared to 60% in patients receiving PVAI alone (P = 0.18). CONCLUSIONS: DF and CFE regions overlap only about 50%. AF termination retrospectively occurred on overlapping CFE/DF sites where DF was above the mean. However, prospective ablation of DF sites plus PVAI resulted in low AF termination rates, and did not improve 1 year success over PVAI alone.

Clinical predictors of arrhythmia recurrences following pulmonary vein antrum isolation for atrial fibrillation: predicting arrhythmia recurrence post-PVAI.

INTRODUCTION: Pulmonary vein antrum isolation (PVAI) is an accepted treatment for atrial fibrillation (AF) refractory to medical therapy. The purpose of this study was to identify the patient, procedural, and follow-up factors associated with arrhythmia recurrences following PVAI. METHODS AND RESULTS: Clinical data were prospectively collected on all 385 consecutive patients who had 530 PVAI (age 58 ± 11 years, 63% paroxysmal AF-PAF, follow-up 2.8 ± 1.2 years) between February 2004 and March 2009. ECGs were recorded at each follow-up visit with Holter monitoring 1, 3, 6, and 12 months following PVAI and every 6 months thereafter. Recurrences < 3 months post-PVAI were defined as early, 3 months-1 year post-PVAI as late, and > 1 year post-PVAI as very late. Relationship between predictor variables and outcomes was modeled using Cox proportional hazards analysis. Late recurrences occurred in 42% with a lower rate among PAF versus non-PAF patients (39% vs 56%, P = 0.001). Of the 256 patients with ≥ 1-year follow-up, 121 (47%) had no arrhythmia off antiarrhythmic drugs (AADs) 1 year post-PVAI; 36 (30%) of these had a very late recurrence. In multivariate analysis, non-PAF, hypertension, and prior AAD failure predicted recurrence. When entered into the model, early recurrences remained the only predictor of late recurrences. CONCLUSION: Patients with non-PAF, hypertension, and prior failure of multiple AAD were more likely to experience arrhythmia recurrence post-PVAI. Early recurrences were the strongest predictor of late recurrences. Late and very late recurrences following PVAI were common and should be considered when planning long-term AF patient management.

FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase.

Fatty acid transport protein (FATP)2, a member of the FATP family of fatty acid uptake mediators, has independently been identified as a hepatic peroxisomal very long-chain acyl-CoA synthetase (VLACS). Here we address whether FATP2 is 1) a peroxisomal enzyme, 2) a plasma membrane-associated long-chain fatty acid (LCFA) transporter, or 3) a multifunctional protein. We found that, in mouse livers, only a minor fraction of FATP2 localizes to peroxisomes, where it contributes to approximately half of the peroxisomal VLACS activity. However, total hepatic (V)LACS activity was not significantly affected by loss of FATP2, while LCFA uptake was reduced by 40%, indicating a more prominent role in hepatic LCFA uptake. This suggests FATP2 as a potential target for a therapeutic intervention of hepatosteatosis. Adeno-associated virus 8-based short hairpin RNA expression vectors were used to achieve liver-specific FATP2 knockdown, which significantly reduced hepatosteatosis in the face of continued high-fat feeding, concomitant with improvements in liver physiology, fasting glucose, and insulin levels. Based on our findings, we propose a model in which FATP2 is a multifunctional protein that shows subcellular localization-dependent activity and is a major contributor to peroxisomal (V)LACS activity and hepatic fatty acid uptake, suggesting FATP2 as a potential novel target for the treatment of nonalcoholic fatty liver disease.

Dofetilide is safe and effective in preventing atrial fibrillation recurrences in patients accepted for catheter ablation.

AIMS: The aim of this study was to assess the safety and efficacy of dofetilide among patients refractory to other anti-arrhythmic drugs (AADs) and accepted for atrial fibrillation (AF) ablation. METHODS AND RESULTS: One hundred and twenty-seven of 454 patients (69% male, 58% paroxysmal, age 60 +/- 10 years, AF duration 8 +/- 7 years) scheduled for AF ablation between February 2004 and May 2008 were treated with dofetilide. Patients had failed 1.9 +/- 1.1 AADs. Anti-arrhythmic drugs were stopped five half-lives before ablation and 3 months for amiodarone. Patients were followed for 15 +/- 7 months with routine and symptom-driven monitoring. Success was defined as no further AF and partial success as a 50% reduction in frequency/duration of AF episodes. Thirty-six patients started dofetilide 158 +/- 167 days before ablation: 9 had no improvement, 16 experienced partial success, 8 had no further AF, and 2 improved enough to forgo ablation. Seventy-one patients started dofetilide immediately following ablation, of which 14 had no improvement, 22 experienced partial success, and 32 had no further AF. Twenty patients started dofetilide 119 +/- 153 days post-ablation, of which four had no improvement, seven experienced partial success, and nine had no further AF. Six patients discontinued dofetilide during initiation for QT prolongation. CONCLUSION: Dofetilide appears safe and effective in preventing AF in patients refractory to other AADs undergoing catheter ablation.

Silencing of hepatic fatty acid transporter protein 5 in vivo reverses diet-induced non-alcoholic fatty liver disease and improves hyperglycemia.

Non-alcoholic fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate the biological outcome and therapeutic potential of hepatic fatty acid uptake inhibition, we utilized an adeno-associated virus-mediated RNA interference technique to knock down the expression of hepatic fatty acid transport protein 5 in vivo prior to or after establishing non-alcoholic fatty liver disease in mice. Using this approach, we demonstrate here the ability to achieve specific, non-toxic, and persistent knockdown of fatty acid transport protein 5 in mouse livers from a single adeno-associated virus injection, resulting in a marked reduction of hepatic dietary fatty acid uptake, reduced caloric uptake, and concomitant protection from diet-induced non-alcoholic fatty liver disease. Importantly, knockdown of fatty acid transport protein 5 was also able to reverse already established non-alcoholic fatty liver disease, resulting in significantly improved whole-body glucose homeostasis. Thus, continued activity of hepatic fatty acid transport protein 5 is required to sustain caloric uptake and fatty acid flux into the liver during high fat feeding and may present a novel avenue for the treatment of non-alcoholic fatty liver disease.