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BACKGROUND Intracardiac electrogram data remain one of the primary diagnostic inputs guiding complex ablation procedures. However, the technology to collect, process, and display intracardiac signals has known shortcomings and has not advanced in several decades. OBJECTIVE The purpose of this study was to evaluate a new signal processing platform, the PURE EP™ system (PURE), in a multi-center, prospective study. METHODS Intracardiac signal data of clinical interest were collected from 51 patients undergoing ablation procedures with PURE, the signal recording system, and the 3D mapping system at the same time stamps. The samples were randomized and subjected to blinded, controlled evaluation by three independent electrophysiologists to determine the overall quality and clinical utility of PURE signals when compared to conventional sources. Each reviewer assessed the same (92) signal sample sets and responded to (235) questions using a 10-point rating scale. If two or more reviewers rated the PURE signal higher than the control, it was deemed superior. RESULTS A total of 93% of question responses showed consensus amongst the blinded reviewers. Based on the ratings for each pair of signals, a cumulative total of 164 PURE signals out of 218 (75.2%) were statistically rated as Superior for this data set (p

In the past decade, the use of interventional electrophysiological (EP) procedures for the diagnosis and treatment of cardiac arrhythmias has exponentially increased. These procedures usually require fluoroscopy to guide the advancement and frequent repositioning of intracardiac catheters, resulting in both the patient and the operator being subjected to a considerable degree of radiation exposure. Although shielding options such as lead gowns, glasses, and pull-down shields are useful for protecting the operator, they do not lessen the patient’s level of exposure. Furthermore, the prolonged use of lead gowns can exponentiate the onset of orthopedic problems among operators. Recent advancements in three-dimensional cardiac mapping systems and the use of radiation-free imaging technologies such as magnetic resonance imaging and intracardiac ultrasound allow operators to perform EP procedures with minimal or even no fluoroscopy. In this review, we sought to describe the state of fluoroless procedures in EP practice.

Introduction Atrioventricular nodal re-entry tachycardia (AVNRT) is the most common, regular narrow-complex tachycardia. The established treatment is catheter ablation of the AV nodal slow pathway (SP). However, in a select group of patients with long PR intervals in sinus rhythm, SP ablation can lead to AV block due to the absence of robust anterograde conduction through the fast pathway (FP). This report aims to demonstrate that AV nodal FP ablation is a reasonable approach in patients with AVNRT and poor or absent anterograde FP conduction. Methods and results Standard electrophysiology study techniques were used in the electrophysiology laboratory. Catheter ablations were performed using radiofrequency energy. Mapping of intracardiac activation was performed with electroanatomical mapping systems. Outcomes were assessed acutely during the procedure and during routine clinical follow-up. Six patients with first-degree AV block and recurrent AVNRT who underwent ablation of their tachycardia at our institution are presented. One patient underwent ablation of AV nodal SP resulting in high-degree AV block necessitating pacemaker implantation. The remaining five patients underwent ablation of the AV nodal FP guided by electroanatomical mapping of the earliest atrial activation in tachycardia. These five had successful treatment of the tachycardia with preservation of anterograde AV nodal conduction. Mapping and ablation approach to eliminate retrograde FP conduction are described. Conclusion In select patients with AVNRT and poor anterograde FP conduction, retrograde FP ablation is reasonable and is less likely to result in AV block and pacemaker dependency.

Objective To compare the histopathological structure and immunohistochemical characteristics of acquired cholesteatoma in children and adults. Patients and Methods This study was carried out on 40 patients presenting with cholesteatomatous middle-ear disease. Twenty patients were of a pediatric age group (18 years). Patients were admitted to the ENT Department of Alexandria University Hospital. All cholesteatoma specimens were collected intraoperatively and preserved for histopathological examination and immunohistochemical technique using the epidermal growth factor (EGF) monoclonal antibody. Results Histopathological examination of the submitted specimens showed that strips of stratified squamous epithelium with the underlying tissues were fibrous in adults, whereas cellular inflammatory infiltrates were observed in children. The degree of fibrosis was significantly higher in the adult group, whereas the pediatric group had higher inflammatory infiltrate. Immunohistochemical examination indicated significantly higher expression of EGF in children compared with adults both in the matrix and in the perimatrix of acquired cholesteatoma. Conclusion Children with acquired cholesteatoma had higher inflammatory infiltration and significant expression of EGF in both the matrix and the perimatrix with less fibrosis compared with adults, explaining the possible pathogenesis of aggressive behavior of cholesteatoma in children.

Background QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient‐specific conduction characteristics ( PR , qLV, LV ‐paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device‐based algorithm (Sync AV ) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. Methods and Results Seventy‐five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128–300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration ( QRS d) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+Sync AV with 50 ms offset (Mode II ), BiV+Sync AV with offset that minimized QRS d (Mode III ), or LV ‐only pacing+Sync AV with 50 ms offset (Mode IV ). The intrinsic QRS d (162±16 ms) was reduced to 142±17 ms (−11.8%) by Mode I, 136±14 ms (−15.6%) by Mode IV , and 132±13 ms (−17.8%) by Mode II . Mode III yielded the shortest overall QRS d (123±12 ms, −23.9% [ P QRS d prolongation in any patient. QRS narrowing occurred regardless of QRS d, PR , or LV ‐paced intervals, or underlying ischemic disease. Conclusions Post‐implant electrical optimization in already well‐selected patients with left bundle branch block and optimized LV lead position is facilitated by patient‐tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device–based algorithm.

Left atrial appendage closure has been increasingly accepted as an alternative to long-term oral anticoagulation (OAC) for stroke prevention in atrial fibrillation patients who are at increased bleeding risk [(1)][1]. PROTECT-AF (The Watchman Left Atrial Appendage System for Embolic Protection in

Background— The implantation of left atrial appendage closure device (WATCHMAN, Boston Scientific, Natick, MA) is an alternative option to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation. Patients require short-term OAC after implantation to avoid device thrombosis. The 2 clinical trials that assessed this device excluded patients thought not to be candidates for OAC. As such, little is known about the safety of this strategy in patients with previous major bleeding events. Methods and Results— All 20 consecutive patients with history of spontaneous major bleeding while on OAC who had subsequently undergone WATCHMAN device implantation at our institution were included. A newly conceived multidisciplinary Atrial Fibrillation Stroke Prevention Center evaluated patients for candidacy for device implantation and subsequent antithrombotic therapy. The primary outcome was spontaneous major bleeding while receiving short-term postprocedural OAC. Median CHA 2 DS 2 -VASc and HAS-BLED scores were 5 (quartiles 5–6) and 5 (quartiles 4–5), respectively. Previous major bleeding events were major gastrointestinal bleeding, intracranial bleeding, spontaneous hemopericardium with cardiac tamponade, and hemarthrosis in 11, 7, 1, and 1 patients, respectively. None of the patients had spontaneous major bleeding during the course of OAC after device implantation. In 1 patient, OAC was discontinued after 40 days because of mechanical fall with head trauma resulting in subdural hematoma with no associated neurological deficits; this was managed conservatively. Conclusions— With careful multidisciplinary evaluation, a short course of OAC after WATCHMAN device implantation in patients with previous spontaneous major bleeding events is associated with low risk of recurrent spontaneous major bleeding.

Background— Various ablation strategies of persistent atrial fibrillation (PersAF) have had disappointing outcomes, despite concerted clinical and research efforts, which could reflect progressive atrial fibrillation–related atrial remodeling. Methods and Results— Two-year outcomes were assessed in 1241 consecutive patients undergoing first-time ablation of PersAF (2005–2012). The time intervals between the first diagnosis of PersAF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide and C-reactive protein before the procedures. The median diagnosis-to-ablation time was 3 years (25th–75th percentiles 1–6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in recurrence rates in addition to an increase in B-type natriuretic peptide levels ( P =0.01), C-reactive protein levels ( P P =0.03). The arrhythmia recurrence rates over 2 years were 33.6%, 52.6%, 57.1%, and 54.6% in the first, second, third, and fourth quartiles, respectively ( P categorical P P categorical Conclusions— In patients with PersAF undergoing ablation, the time interval between the first diagnosis of PersAF and the catheter ablation procedure had a strong association with the ablation outcomes, such as shorter diagnosis-to-ablation times were associated with better outcomes and in direct association with markers of atrial remodeling.

Background There are limited published data regarding the percutaneous extraction of device leads jailed by a venous stent. Objective In this study we assessed the feasibility and safety of percutaneous extraction of stented device leads. Methods We reviewed our experience percutaneously extracting 7 chronically implanted device leads jailed to the wall of the left innominate and/or subclavian veins by a previously placed stent. Results All leads were successfully extracted by using a percutaneous approach. Both pacing leads and defibrillator leads were extracted. The oldest pacing lead extracted was 14 years old. The oldest defibrillator lead extracted was 6 years old. Three of the leads were extracted with simple manual traction alone. The 4 remaining leads required a more complex, femoral extraction approach for successful removal. Conclusion In our experience extracting 7 stented device leads, complete percutaneous removal was feasible 100% of the time using a combination of simple manual traction and a femoral approach. No major complications were associated with the extraction procedures.

Objective To compare the histopathological structure and immunohistochemical characteristics of acquired cholesteatoma in children and adults. Study design Prospective clinical study in a tertiary care centers. Material & methods This study was conducted on 40 patients presenting with cholesteatomatous middle ear disease. Twenty patients were of a pediatric age group ( 18 years). Patients were admitted to either the ENT Department of Alexandria University Hospital or that of the Students’ Hospital. All cholesteatoma specimens were collected intra-operatively and preserved for histopathological examination and immunohistochemical technique (PCNA monoclonal antibody). Results Histopathological examination of the submitted specimens revealed that strips of stratified squamous epithelium with the underlying tissues were fibrous in adults while cellular inflammatory infiltrates were seen in children. The degree of fibrosis was significantly higher in the adult group. Immunohistochemical examination revealed significantly higher expression scores of the proliferation marker in the pediatric group. In the matrix: The mean of PCNA/LI of adult squamous epithelium was 17.75 ± 12.08 and of children’s cases was 32.82 ± 17.09. In the perimatrix: The mean of PCNA/LI of adult inflammatory infiltrate was 14.77 ± 17.28 and in children was 24.22 ± 22.61. The differences of both were statistically significant. Conclusion The degree of fibrosis was significantly higher in adult specimens indicating a reparative process and less invasiveness. PCNA expression was significantly higher in the matrix and perimatrix of pediatric cholesteatoma as correlated to its increased proliferation. Pediatric cholesteatoma was more aggressive and invasive than adult cholesteatoma.

Introduction: Persistent atrial fibrillation (PerAF) ablation has been associated with significant recurrence rates which could reflect progressive AF-related atrial remodeling. We hypothesized that the first-diagnosis to ablation time for PerAF is a major determinant of success rates and in direct association with pathways of atrial remodeling. Methods: Two-year outcomes were assessed in 1241 patients undergoing first time ablation of PerAF between January 2005 and December 2012 at our institution. The time intervals between the first diagnosis of PerF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) before the ablation procedures. During ablations, patients with atrial scarring by voltage were identified. Results: The median time-to-ablation since the first PerAF diagnosis was 3 years (interquartile range 1-6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in BNP levels (p=0.01), CRP levels (p Conclusions: The success rates with PerAF ablation are highest with early intervention, that is ablation before the progression of atrial remodeling.

Objectives This study sought to report on the safety of catheter ablation for atrial fibrillation (AF) in patients with prior cerebrovascular events (CVEs), at a large-volume tertiary care center over the course of the past 15 years. Background Many patients with drug-refractory AF have a history of a prior CVE. These patients are considered to be at high procedural risk for catheter ablation but data are scant. Methods All consecutive patients undergoing AF ablation at the Cleveland Clinic were enrolled in a prospectively maintained data registry, which was used to identify patients with a prior CVE. Strict periprocedural anticoagulation protocols were in place. Extreme care was taken with sheath and catheter manipulation to prevent thrombus formation or air embolism. All thromboembolic and hemorrhagic events occurring periprocedurally and up to 3 months of follow-up were identified. Results Of 9,413 consecutive patients who underwent AF ablation, 247 patients with a prior CVE were identified (median age, 64 years; 40.1% female; median CHA2DS2-VASC score, 4). Anticoagulants used were warfarin (n = 192), dabigatran (n = 32), rivaroxaban (n = 15), and apixaban (n = 8). All patients received intravenous heparin before transseptal access (activated clotting time target during procedure, 350 to 400 seconds). The energy source was radiofrequency in 242 patients and cryoenergy in 5 patients. Acute procedural complications included 5 groin hematomas (1 requiring transfusion), 5 pericardial effusions with associated tamponade physiology in 2 (1 required pericardiocenthesis, 1 required surgery), and 1 arteriovenous fistula (managed conservatively). Importantly, none of the patients had a periprocedural thromboembolic event. Conclusions Patients with a prior history of cerebrovascular events do not seem to be predisposed to a significant risk of clinical CVE recurrence when undergoing catheter ablation for AF without interruption of therapeutic anticoagulation.

Patients with ambulatory New York Heart Association (NYHA) class IV heart failure were significantly underrepresented in clinical trials of cardiac resynchronization therapy (CRT). The natural long-term trajectory of survival free of left ventricular assist device (LVAD) or heart transplant in patients with ambulatory class IV symptoms who underwent CRT has not been established. We extracted clinical data on 723 consecutive patients with NYHA class III or ambulatory class IV heart failure, left ventricular ejection fraction ≤35%, and a QRS duration ≥120 ms who underwent CRT from September 30, 2003, to August 6, 2007. Chart notes immediately before CRT were reviewed to confirm NYHA class status before CRT. Kaplan-Meier curves and a multivariate Cox proportional hazards model were constructed to determine long-term survival free of heart transplant and LVAD based on NYHA class status. Of the 723 patients, 52 had ambulatory class IV symptoms. Over a mean follow-up of 5.0 ± 2.5 years controlling for many possible confounders, ambulatory NYHA class IV status was independently associated with poor long-term outcomes. The 1-, 2-, 3-, 4-, and 5-year survival free of LVAD or heart transplant for class III versus ambulatory class IV patients was 92.0%, 84.0%, 75.0%, 68.1%, and 63.2% versus 75.0%, 61.5%, 52.0%, 45%, and 40.4%, respectively. Although patients with ambulatory class IV heart failure receiving CRT have inferior long-term outcomes compared with those with class III symptoms, survival in class IV patients continues to parallel class III patients over an extended follow-up. At 5 years, survival free of LVAD or heart transplant in ambulatory class IV patients receiving CRT is 40%.

We studied the human leukocytes antigens in 18 Egyptian children with biliary atresia (BA) without extrahepatic congenital malformations. There was a significant increased frequency of both B8 and DR3 (83.3% and 94.4% in patients with BA compared with 6.5% and 14.9% in the general population, respectively). Ten patients had the B8/DR3 haplotype. Our results support the hypothesis that genetic factors may play a role in susceptibility to BA. (J Pediatr 2002;141:432-4)

Background and Purpose We aimed to determine the effect of intracisternal administration of an endothelin-A receptor antagonist (BQ-123) against vasospasm in a monkey model and to determine whether this drug would have adverse interactions with intracisternal tissue plasminogen activator (TPA). Methods Thirty-three monkeys were randomly allocated to undergo baseline cerebral angiography, creation of right subarachnoid hemorrhage (SAH), and intracisternal delivery of (1) placebo (n=10); (2) low-dose BQ-123 (5 mg/kg per day, n=7); (3) high-dose BQ-123 (10 mg/kg per day, n=9); or (4) BQ-123 10 mg/kg per day plus TPA 1 mg every 12 hours for three doses (n=7). Angiography was repeated after 7 days, and animals were killed. Vasospasm was assessed by comparisons of angiograms within groups across time by paired t test and by comparisons across groups at each time by ANOVA. Results Significant clot remained in the basal cisterns in all groups except those receiving TPA, in whom complete clot clearance was noted. Comparisons of angiograms at baseline and after 7 days showed significant vasospasm of the right middle cerebral artery in animals receiving placebo (mean±SEM reduction in diameter, 36±7%; P Conclusions Intracisternal TPA was efficacious against vasospasm in monkeys. Combination therapy with TPA and BQ-123 was not associated with reduction in efficacy of either drug or with evidence of toxicity.