Background The PINNACLE FLX (Protection Against Embolism for Non-valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next-generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2-year outcomes with this next-generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA2DS2-VASc, 4.2±1.5), the secondary efficacy end point of 2-year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1-sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two-year rates of adverse events were as follows: 9.3% all-cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device-related thrombi after 1 year. Conclusions The secondary end point of 2-year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next-generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Among 31 patients with pemphigus, we observed two women with clinical and histologic features characteristic of pemphigus vulgaris that later became those of pemphigus foliaceus. Western blot study indicated that serum from one patient, when she had the cutaneous manifestations of pemphigus foliaceus, contained antibodies reactive with a desmosomal antigen, suggestive of desmoglein 1, the same as recognized by pemphigus foliaceus serum. The present study suggests that two distinct types of pemphigus can occur in the same person simultaneously or separately.

OBJECTIVES STOP AF PAS (Sustained Treatment of Paroxysmal Atrial Fibrillation Post-Approval Study) is the first prospective, multicenter, 3-year study in North America to assess long-term safety and effectiveness of the cryoballoon for treatment of patients with drug-refractory symptomatic pAF. BACKGROUND The STOP AF PAS was required by the U.S. Food and Drug Administration at the time of approval of the first-generation cryoballoon for the treatment of paroxysmal atrial fibrillation (pAF). The second-generation cryoballoon (CB2) was commercially released shortly after this trial was initiated. METHODS The study was nonrandomized. Enrollment was completed with 344 eligible patients undergoing pulmonary vein isolation (PVI) using the CB2. Procedure-related safety and freedom from AF and symptomatic atrial flutter/atrial tachycardia through 3 years were determined. Documented atrial arrhythmias >= 30 s were considered treatment failures. RESULTS Acute PVI was achieved in 99.3% (1,341 of 1,350) of veins. Mean follow-up was 34 +/- 7 months. The rate of major complications was 5.8%, including a 3.2% rate of phrenic nerve injury, which resolved in all but 1 patient by 36 months. At 36 months, 11.7% of patients were prescribed antiarrhythmic agents, inclusive of "pill-in-the-pocket" administration. Freedom from AF was 81.6% at 12 months, 73.8% at 24 months, and 68.1% at 36 months. Freedom from AF and symptomatic atrial flutter/atrial tachycardia was 79.0% at 12 months, 70.8% at 24 months, and 64.1% at 36 months. Freedom from a repeat ablation procedure was 80.9% at 36 months. CONCLUSIONS PVI using the CB2 was an effective treatment for patients with pAF, with freedom from all atrial arrhythmias of 64% at 36 months. (Sustained Treatment of Paroxysmal Atrial Fibrillation Post-Approval Study [STOP AF PAS]; NCT01456949) (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

BACKGROUND:Pulmonary vein isolation by catheter ablation is a class IA indication for the treatment of symptomatic, drug-refractory, paroxysmal atrial fibrillation (PAF). Quality of life (QoL) has been identified as a clinically meaningful endpoint but has not been comprehensively evaluated to date.OBJECTIVE:The purpose of this study was to evaluate the effects of cryoballoon ablation on long-term QoL.METHODS:As part of the STOP-AF Post-Approval Study, QoL was assessed using the Short Form-12 Health Survey (SF-12) along with evaluation of arrhythmia-related symptoms through 36 months. A multivariate linear mixed effects regression was used to determine the association between atrial fibrillation symptoms and QoL scores, and univariate linear regressions were used to assess predictors of 36-month change in QoL scores.RESULTS:Three hundred thirty-five subjects fully completed SF-12 forms at baseline, with 319, 308, 291, and 278 subjects completing surveys at the subsequent follow-up visits. Both physical and mental composite scores increased significantly from baseline (P <.001), and all arrhythmia symptoms significantly decreased from baseline (P <.001), with 62.0% of subjects reporting no symptoms at 6 months compared to 5.7% at baseline (P <.001). Presence of dyspnea and fatigue at baseline were univariate predictors of physical QoL improvement (P = .045 and 0.0497, respectively), whereas each year of age and each year of PAF duration were predictors of a decrease in mental QoL (P = .014 and .04, respectively).CONCLUSION:Cryoballoon ablation for treatment of PAF results in a significant, and sustained, QoL improvement. The observed improvement in physical and mental health likely may be mediated by a reduction in symptom and arrhythmia burden.

Background: A cardiac lead with a side helix for active fixation to the coronary vein wall (Attain Stability((R)), Model 20066, Medtronic, Minneapolis, MN, USA) recently received CE Mark. The lead is designed to improve left ventricular (LV) placement and reduce dislodgement rates. The extractability of this active fixation LV lead has not been studied extensively. Methods: Seventeen sheep were implanted with either an LV lead with a side helix (Model 20066, Model 20096, Medtronic) or a unipolar LV lead (Model 4193, Medtronic) as a control. Leads were extracted at approximately 26, 52, or 118weeks. Standard extraction methodology was employed with quantitative traction up to 907g (2 lbs.) using a locking stylet. Gross pathology and histology of the heart with particular attention to the lead tracts were performed. Results: All leads were successfully removed in their entirety and required significantly less than 1kg of traction force. The side helix disengaged from the vein as designed and resulted in no complications. No cardiac tissue was observed on any extracted lead. Gross pathology and histology were devoid of any helix-induced lesions in the vascular structures. The epicardium over the side helix was normal and the fibrotic reaction around the helix was not significantly different from that around the nonhelix portions of the study leads or the control lead. Conclusion: Extraction of the side helix, active fixation LV lead from the coronary veins in the sheep model is safe, without procedural complexity, and free of complications after long-term LV lead implant duration.

Purpose: The purpose of this interim analysis was to determine the impact of cryoballoon ablation, using the second generation cryoballoon, on AF symptoms and quality of life (QOL) at 12 months post-ablation in patients with drug-refractory recurrent symptomatic paroxysmal AF. Methods: The STOP-AF Post Approval Study (PAS) is a prospective, multi-center, non-randomized, single-arm, unblinded, condition of approval study, designed to provide long-term safety and efficacy data for cryoballoon ablation. A total of 402 patients at 39 sites from the United States and Canada are participating in the study. Changes in arrhythmic symptoms and QOL (using the SF-12 Health Survey) are assessed at baseline, 6 months, 12 months, and annually thereafter. Results: At the time of this interim analysis, 304 patients (67% male; 60 ± 10 years of age; with AF onset 4.7 ± 5.6 years prior to baseline) treated with the second generation cryoballoon for drug-refractory, recurrent symptomatic paroxysmal AF completed symptom evaluations at both baseline and 12 months. At 12 months post-ablation, there was a 56% reduction in arrhythmic symptoms. This symptomatic improvement was confirmed by significant improvement in SF-12 scores in patients reporting QOL at 12 months post-ablation. The SF-12 mean physical component score improved from 45.3 to 50.1 (p < 0.01) and the mental component scores improved from 49.4 to 53.0 (p < 0.01). Arrhythmia-related symptom reduction was statistically significant (p < 0.01) 12 months post-ablation for all patient symptoms: dizziness (35.5% to 6.3%), palpitations (74.0% to 25.0%), rapid heartbeat (39.5% to 9.2%), dyspnea (41.1% to 8.2%), fatigue (57.2% to 7.9%), and syncope (5.3% to 0.0%). Conclusions: Patients treated with the second generation cryoballoon demonstrated a significant improvement in arrhythmia related symptoms and QOL from baseline to 12 months post-ablation.

Purpose: The purpose of this interim analysis was to report the safety and 12 month efficacy from the largest prospective multi-center trial evaluating cryoballoon ablation using the second generation cryoballoon (CB2) in the United States and Canada. Methods: The STOP-AF post approval study is a prospective, multi-center, non-randomized study designed to provide long-term safety and efficacy data for cryoballoon ablation. Safety data is presented on the final enrolled cohort of patients treated with CB2 (n = 345). Freedom from atrial fibrillation (AF) and symptomatic atrial flutter (AFL) / tachycardia (AT) is presented for patients who had a minimum of 12 months follow-up at the time of this interim analysis (n = 338). Kaplan-Meier estimate was utilized for calculating the primary endpoint. Documented AF lasting longer than 30 seconds and/or a repeat ablation after the 90-day blanking period were considered treatment failures. Results: Upon completion of enrollment, 345 patients were treated with CB2 for drug-refractory, recurrent symptomatic paroxysmal AF. Acute pulmonary vein isolation (PVI) was achieved in 99.4% (343/345) of patients. Of the 345 patients, 338 (98%) had a minimum of 12-months follow-up (mean follow-up 17 ± 7 months). Freedom from AF at 12 months was 82.8% (95% CI: 78.2% to 86.5%) and freedom from AF and symptomatic AFL/AT was 80.0% (95% CI: 75.3% to 84.0%). Phrenic nerve injury (PNI) was unresolved at hospital discharge in 11 patients (3.2%). PNI resolved in 8/11 patients (mean time to resolution = 125 days) and was still present after 12 months in 3 patients (0.9%). Other major events included: cerebrovascular accident (0.3%), PV stenosis (0.6%), pericardial effusion (0.6%), tamponade (0.3%), and hemoptysis (0.9%). No device or procedure related deaths occurred. Conclusions: PVI using the CB2 is a highly effective treatment for patients with drug-refractory recurrent symptomatic paroxysmal AF. This analysis reports freedom from AF of 82.8%, and freedom from all atrial arrhythmias of 80.0% at 12 months. PNI ongoing beyond 12 months is observed in less than 1% of patients.

Transseptal catheterization of the interatrial septum has traditionally been performed under the guidance of fluoroscopy, echocardiography, and hemodynamic pressure monitoring. We hypothesized that the fossa ovalis could be identified on pre-ablation chest computerized tomography (CT) scan utilizing EnSite Verismo™ and Fusion™ software thereby permitting its real-time visualization during transseptal puncture.

BACKGROUND:Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial.METHODS AND RESULTS:A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics.CONCLUSIONS:Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial.

Objectives This study sought to examine the safety and efficacy of laser-assisted lead extraction and the indications, outcomes, and risk factors in a large series of consecutive patients.Background The need for lead extraction has been increasing in direct relationship to the increased numbers of cardiovascular implantable electronic devices.Methods Consecutive patients undergoing transvenous laser-assisted lead extraction at 13 centers were included.Results Between January 2004 and December 2007, 1,449 consecutive patients underwent laser-assisted lead extraction of 2,405 leads (20 to 270 procedures/site). Median implantation duration was 82.1 months (0.4 to 356.8 months). Leads were completely removed 96.5% of the time, with a 97.7% clinical success rate whereby clinical goals associated with the indication for lead removal were achieved. Failure to achieve clinical success was associated with body mass index <25 kg/m(2) and low extraction volume centers. Procedural failure was higher in leads implanted for >10 years and when performed in low volume centers. Major adverse events in 20 patients were directly related to the procedure (1.4%) including 4 deaths (0.28%). Major adverse effects were associated with patients with a body mass index <25 kg/m(2). Overall all-cause in-hospital mortality was 1.86%; 4.3% when associated with endocarditis, 7.9% when associated with endocarditis and diabetes, and 12.4% when associated with endocarditis and creatinine >= 2.0. Indicators of all-cause in-hospital mortality were pocket infections, device-related endocarditis, diabetes, and creatinine >= 2.0.Conclusions Lead extraction employing laser sheaths is highly successful with a low procedural complication rate. Total mortality is substantially increased with pocket infections or device-related endocarditis, particularly in the setting of diabetes, renal insufficiency, or body mass index <25 kg/m(2). Centers with smaller case volumes tended to have a lower rate of successful extraction. (J Am Coll Cardiol 2010;55:579-86) (c) 2010 by the American College of Cardiology Foundation

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RV(a)) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RV(a), left ventricular free wall (LV(fw)), and the combination of RV(a) and LV(fw) (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RV(a) and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCA(long)) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LV(fw) pacing. RV(a) (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RV(a) than LV(fw) pacing. In patients with normal LV function, acute ventricular pacing in the RV(a) alone, or in conjunction with LV(fw) pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LV(fw) pacing alone.

BACKGROUND Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in appropriately selected patients with heart failure. Optimal left ventricular (LV) lead placement is useful in enhancing response from CRT. Three significant obstacles to LV lead placement are patient-specific variations in coronary venous anatomy, phrenic nerve stimulation, and a significant rate of LV lead dislodgement or microdislodgement.OBJECTIVE The primary objective of this study was to determine the safety and effectiveness of the Medtronic StarFix active fixation LV lead. Secondary objectives evaluated implant success, lead placement and procedure time, lead handling and lobe deployment, additional electrical performance, and all adverse events reported in the study.METHODS There were 441 patients enrolled in this multicenter study. Standard cardiac resynchronization therapy (CRT) inclusion criteria were used. Patients were followed up for a mean of 23 months. Implant data, success with CRT, LV lead performance, clinical outcomes, and experience with LV lead revisions were prospectively evaluated.RESULTS The mean LV stimulation threshold at implant was 1.3 +/- 1 volts and was stable over time. Sensing was also excellent. In 96.3% of the implantations in this study, the physician was able to place the lead in a nonanterior position. Extracardiac (phrenic nerve) stimulation required invasive intervention in 11 subjects (2.5%). Only 3 dislodgements (0.7%) were observed. Two occurred in the first 5 implants and were attributed to inadequate engagement of the venous subbranch.CONCLUSION The Medtronic 4195 is safe and highly efficacious. It affords the physician more choices in lead placement location and has a remarkably low dislodgement rate.

A recent report from IMPROVE HF demonstrated wide variations among hospitals and that subgroups (e.g. women and older patients) were less likely to receive devices. We sought to identify factors influencing device utilization in a large cardiology practice (36 physicians). The integrated HF team utilizes protocols and cross-referrals between 6 HF cardiologists, 6 electrophysiologists and 3 Nurse Practitioners with specialty training in HF. The backbone of all quality efforts is a comprehensive database that included measures of HF severity, rates of evidence based therapy and outcomes. We included ALL patients who had at least one clinic visit over 3 years (2006-08). The database included 3, 124 patients (mean age 70.2 years). Most were males (63%). Etiology was ischemic heart disease (39.6%) or idiopathic (39.9%). There were 1,513 patients with LVEF < 35%. This group had frequent co-morbidities: atrial fibrillation 37.4%, diabetes 27.9%, renal insufficiency 21.0% and COPD 17.9%; 52.3% had 2 or more co-morbidities. Patients with LVEF < 35% were treated with ACE/ARB (94.7%) and beta blockers (95.6%). There were a total of 863 devices (overall 57.1%) including CRT-P (2.5%), CRT-D (28.1%), upgrade ICD to CRT-D (8.5%) and ICD alone (18.0%). Total device therapies were more frequent in males (61.3%) vs. females (47.7%), patients with ischemic (73.4%) vs. idiopathic etiology (46.4%) and in older age groups, such as >75 years (63.5%) vs. 65-75 years (62.0%) and < 65 years (46.6%). Further, device use was more common when a co-morbidity was present, compared to when it was absent, such as atrial fibrillation (63% vs. 53.2%) and renal insufficiency (64.8% vs. 47.6%), consistent with the "sicker patient." Most of the gender gap between could be explained by the increase incidence of ischemic disease and co-morbidities in males. These data represent the largest database on outpatient ("real world") HF therapies from a single cardiology practice. These data demonstrate that a HF team working within a practice can achieve high rates of utilization of evidence based therapies. These data confirm higher rates of device utilization among males and patients with ischemic heart disease and additionally demonstrate higher rates among older patients and those with co-morbidities. These data suggest that the variations in device utilization are influenced by differences in patient populations.

Background: Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT.Methods and Results: Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI] speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation.Conclusions: Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline C mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT. (J Cardiac Fail 2009;15:401-409)

The current study assessed the acute effects of pacemaker optimization (PMO) on cardiac function using echocardiographic (ECHO) tissue Doppler imaging (TDI) in the post CRT setting. Data were analyzed from 50 consecutive patients clinically referred for PMO. Patients underwent a sequential ECHO/TDI-guided PMO study to determine optimal pacemaker settings. In 34 of 50 patients a change in pacemaker settings was made because of an objective improvement in ECHO/TDI findings. Overall, significant improvements were observed for ECHO/TDI measures of systolic function (global systolic contraction score, p < 0.001; ejection time, p < 0.05), diastolic function (diastolic filling period, p < 0.01; mitral velocity-time integral, p < 0.05) and left ventricular (LV) dyssynchrony (standard deviation of time to peak displacement, p < 0.05). In most patients referred for chronic PMO, ECHO/TDI-guided PMO can be used to objectively improve cardiac systolic function, diastolic function and/or LV dyssynchrony.

BACKGROUND:The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF.METHODS AND RESULTS:Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03).CONCLUSION:Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.