DeSimone, Christopher V.

Abstract Objective To investigate the influence of acetylsalicylic acid (ASA) use on risk and outcome of community-acquired Staphylococcus aureus bacteremia (CA-SAB). Method We used population-based medical databases to identify all patients diagnosed in northern Denmark with first-time CA-SAB and matched population controls from 2000–2011. Categories for ASA users included current users (new or long-term users), former users, and nonusers. The analyses were adjusted for comorbidities, comedication use, and socioeconomic indicators. Results We identified 2638 patients with first-time CA-SAB and 26 379 matched population controls. Compared with nonusers, the adjusted odds ratio (aOR) for CA-SAB was 1.00 (95% confidence interval [CI], 0.88–1.13) for current users, 1.00 (95% CI, 0.86–1.16) for former users, 2.04 (95% CI, 1.42–2.94) for new users, and 0.95 (95% CI, 0.84–1.09) for long-term users. Thirty-day cumulative mortality was 28.0% among current users compared with 21.6% among nonusers, yielding an adjusted hazard rate ratio (aHRR) of 1.02 (95% CI, 0.84–1.25). Compared with nonusers, the aHRR was 1.10 (95% CI, 0.87–1.40) for former users, 0.60 (95% CI, 0.29–1.21) for new users, and 1.06 (95% CI, 0.87–1.31) for long-term users. We observed no difference in the risk or outcome of CA-SAB with increasing ASA dose or by presence of diseases commonly treated with ASA. Conclusions Use of ASA did not seem to influence the risk or outcome of CA-SAB. The apparent increased risk among new users may relate to residual confounding from the circumstances underlying ASA treatment initiation. Our finding of no association remained robust with increasing ASA dose and across multiple patient subsets.

Abstract Background Choosing the appropriate animal model for development of novel technologies requires an understanding of anatomy and physiology of these different models. There are little data about the characteristics of different animal models for the study of technologies used for epicardial ablation. We aimed to compare the incidence of ventricular arrhythmias during epicardial radiofrequency ablation between swine and canine models using novel epicardial ablation catheters. Methods We conducted a retrospective study using data obtained from epicardial ablation experiments performed on swine ( Sus Scrofa ) and canine ( Canis familiaris ) models. We compared the incidence of ventricular arrhythmias during ablation between swine and canine using multivariate regression analysis. Six swine and six canine animals underwent successful epicardial radiofrequency ablation. A total of 103 ablation applications were recorded. Results Ventricular arrhythmias requiring cardioversion occurred in 13.11% of radiofrequency ablation applications in swine and 9.75% in canine (relative risk: 117.6%, 95% confidence interval [CI]: 83.97‐164.69, animal‐based odds ratio [OR]: .55, 95% CI: .23‐61.33; P = .184). When adjusting for application position, duration of ablation and power, the odds of developing potentially lethal ventricular arrhythmia in swine increased significantly compared to canine (OR: 3.60, 95% CI: 1.35‐9.55; P = .010). Conclusions The swine myocardium is more susceptible to developing ventricular arrhythmias compared to canine model during epicardial ablation. This issue should be carefully considered in future studies.

AbstractIntroductionIt is unknown if ANO‐1 is expressed in the heart, though the presence of a calcium‐activated chloride current has been proposed to mediate some cardiac dysrhythmias. Furthermore, a specific cell type termed telocytes, morphologically mimicking Cajal cells which use ANO‐1 to modulate their pacemaker activity in the gut, have been described in the heart. We therefore sought to determine whether this channel is expressed in the canine heart.MethodsMyocardium was sampled from the ventricles of five canines. Sections were labeled with anti‐Kit and anti‐ANO‐1 antibodies. Slides were reviewed by four investigators looking at cell morphology, distribution, and co‐localization. Identification of telocytes was based on criteria including morphology, Kit positivity (+), and ANO‐1 positivity (+).ResultsClusters of cells meeting criteria for telocytes were seen in the epicardium, sub‐epicardium, and mid‐myocardium. A small subset of cells that were morphologically similar to myocytes was ANO‐1 (+) but Kit (−). In total, three different cell classes were found: (i) Kit (+), ANO‐1 (+) cells with the appearance of telocytes; (ii) Kit (+), ANO‐1 (−) cells; and (iii) Kit (−), ANO‐1 (+) cells with the morphologic appearance of cardiac myocytes.ConclusionsTelocytes are present in the canine ventricle and express ANO‐1. These data merit further study to elucidate the functional expression of these channels in the heart and whether they may be targets for cardiac arrhythmias.

Background The Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation ( IRE ) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE . Methods and Results In an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90‐μs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T‐wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250–833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV ( P =0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J ( P =0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J. Conclusions Our study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

Background Current thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period. Methods and Results Initial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present. Conclusions Irreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.

AbstractBackgroundCardiovascular implantable electronic devices (CIEDs) can be life‐saving. However, complications from CIED infection can be life‐threatening, often requiring device removal. Despite publication of CIED infection management guidelines, there remains marked variation in clinical practice.ObjectiveTo better understand and quantify these differences, we conducted a multinational survey of practitioners of CIED management.MethodsAn electronic survey was sent to Heart Rhythm Society members, spanning 70 countries across six continents. All responses were collected anonymously.Results227 out of 3,600 (6.3%) responded to the survey. The majority of surveys were completed by practitioners from the United States (168; 68.3%) and 53.8% of these practiced in academic medical centers. The large majority (92.7%) of sites had protocols to ensure appropriate timing of prophylactic antibiotics. Superficial (incisional) site infections were treated with antibiotics alone 52.5% of the time (consistent with guidelines); in contrast, deep pocket infections were treated with antibiotics (with device removal) in accordance to guidelines only 37.4% of the time. Almost all providers (98.7%) were inclined to perform complete hardware removal in cases of CIED‐related endocarditis. In contrast, 82.2% of survey participants suggested complete CIED system removal in patients with an occult Gram‐positive bacteremia, 65.5% with occult Gram‐negative bacteremia, and 59.3% with prolonged bacteremia due to a source other than CIED.ConclusionsThese data suggest wide variability in clinical practice in managing CIED infection with significant deviations from published guidelines. There is critical need to increase awareness and develop institutional protocols to ensure adherence with evidence‐based guidelines to optimize outcomes.