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RF Ablation of VT in Chronic Cocaine Users Background Cocaine use is a known but rare cause of cardiac arrhythmias. Ventricular arrhythmias related to cocaine may not respond to antiarrhythmic drugs and may need treatment with radiofrequency ablation. Objectives We describe the clinical and electrophysiological characteristics of cocaine-related ventricular tachycardia (VT) from a multicenter registry. Methods Subjects presenting with VT related to cocaine use and being considered for radiofrequency ablation have been included in the study. Patients who were refractory to maximal medical therapy underwent radiofrequency ablation of the VT. Clinical, procedural variables, efficacy, and safety outcomes were assessed. Results A total of 14 subjects met study criteria (age 44 ± 13, range 18- to 68-year-old with 79% male, 71% Caucasian). MRI showed evidence of scar only in 43% of patients (6/14). The mechanism of VT was focal in 50% (n = 7) and scar related reentry in 50% (n = 7) based on 3D mapping. The mean VT cycle length was 429 ± 96 milliseconds. The site of origin was epicardial in 16% (3/18) of VTs. Most clinical VTs were hemodynamically stable (75%). Mean ejection fraction at the time of admission was 44 ± 14%. Duration of procedure was 289 ± 50 minutes. One subject developed pericardial tamponade requiring drainage. At 18 ± 11 months follow-up, freedom from arrhythmia was seen in 86% (1 case lost to follow-up and 2 died). Conclusion Radiofrequency ablation is not only feasible but also safe and effective in patients who have drug refractory VT related to chronic cocaine use. © 2014 Wiley Periodicals, Inc.

Introduction: Hemostasis following large-bore femoral vein access remains a challenge. Manual compression has been the standard of care but requires bedside staff, prolonged bed rest, and longer length of stay. The LockeT is an external compression device that attempts to address these issues while achieving venous hemostasis., Objectives: We evaluate postprocedural hemostasis and vascular closure outcomes after using LockeT following cardiac electrophysiologic procedures., Methods: We performed a single-center, observational study of patients who underwent vascular closure for electrophysiology procedures using LockeT. Postprocedural outcomes were subsequently analyzed., Results: We studied 102 patients (N) for whom LockeT was used to close 182 separate vascular access sites (n). Common procedures were atrial fibrillation ablation (56.9%, N = 58) and left atrial appendage occlusion (28.4%, N = 29). Most often, 8-Fr [48.3% (n = 126)], 11-Fr [27.2% (n = 71)], and 8.5-Fr [16.9% (n = 44)] sheaths were used, with an average procedure time of 82.1 ± 29.4 min. Hemostasis was achieved in 97.8% (n = 187) of all LockeT cases. Time to ambulation and discharge were 3.93 ± 1.10 h and 8.1 ± 4.4 h, respectively. No major complications were noted. Postprocedurally, 52% (N = 53) of patients were discharged on the same day. There were no differences in hemostasis (p = .859) or ambulation times (p = .202) between procedure types., Conclusion: The LockeT can effectively close venous access sites with no major complications., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: The obligate intracellular bacterial family Chlamydiaceae comprises a number of different species that cause disease in various vertebrate hosts including humans. Chlamydia suis, primarily found in the gastrointestinal tract of pigs, is the only species of the Chlamydiaceae family to have naturally gained tetracycline resistance (TetR), through a genomic island (Tet-island), integrated into the middle of chromosomal invasin-like gene inv. Previous studies have hypothesised that the uptake of the Tet-island from a host outside the Chlamydiaceae family was a unique event, followed by spread among C. suis through homologous recombination. In vitro recombination studies have shown that Tet-island exchange between C. suis strains is possible. Our aim in this study was to gain a deeper understanding of the interclade recombination of the Tet-island, among currently circulating C. suis field strains compared to in vitro-generated recombinants, using published whole genome sequences of C. suis field strains (n = 35) and in vitro-generated recombinants (n = 63)., Results: We found that the phylogeny of inv better reflected the phylogeny of the Tet-island than that of the whole genome, supporting recombination rather than site-specific insertion as the means of transfer. There were considerable differences between the distribution of recombinations within in vitro-generated strains compared to that within the field strains. These differences are likely because in vitro-generated recombinants were selected for a tetracycline and rifamycin/rifampicin resistant background, leading to the largest peak of recombination across the Tet-island. Finally, we found that interclade recombinations across the Tet-island were more variable in length downstream of the Tet-island than upstream., Conclusions: Our study supports the hypothesis that the occurrence of TetR strains in both clades of C. suis came about through interclade recombination after a single ancestral horizontal gene transfer event., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) is the most common arrhythmia reported worldwide. There is significant heterogeneity in AF care pathways for a patient seen in the emergency room, impacting access to guideline-driven therapies., Objectives: The purpose of this study was to compare the difference in AF outcomes between those treated with an organized treatment pathway vs routine-care approach., Methods: The emergency room to electrophysiology service study (ER2EP) is a multicenter, prospective observational registry (NCT04476524) enrolling patients with AF from sites where a pathway for management of AF was put in place compared to sites where a pathway was not in place within the same health system and the same physicians providing services at all sites. Multivariable regression modeling was performed to identify predictors of clinical outcomes. Beta coefficient or odds ratio was reported as appropriate., Results: A total of 500 patients (ER2EP group, n = 250; control group, n = 250) were included in the study. The mean age was 73.4 ± 12.9 years, and 52.2% were males. There was a statistically significant difference in primary endpoint [time to ablation (56 ± 50.9 days vs 183.3 ± 109.5 days; P  < 0.001), time to anticoagulation initiation (2.1 ± 1.6 days vs 19.7 ± 35 days, P  < 0.001), antiarrhythmic drug initiation (4.8 ± 7.1 days vs 24.7 ± 44.4 days, P  < 0.001) compared to the control group, respectively. As such, this resulted in reduced length of stay in the ER2EP group compared to the control group (2.4 ± 1.4 days vs 3.23 ± 2.5 days, P  = 0.002)., Conclusions: This study provides evidence that having an organized pathway from the emergency department for AF patients involving electrophysiology services can improve early access to definitive therapies and clinical outcomes., Competing Interests: This study was supported by an unrestricted research grant from 10.13039/100007497Biosense Webster Inc and sponsored by the Kansas City Heart Rhythm Institute. Dr Lakkireddy is on the Speakers Bureau of Boston Scientific, Biosense Webster, Inc, and Janssen Pharmaceuticals; and has received honoraria/speaking/consulting fees from Abbott, Acutus, AtriCure Inc, Medtronic Inc, Philips, Biotronik, and Cardiovia. Dr Garg has received honoraria/speaking/consulting fees from Biosense Webster and Medtronic. Dr Gopinathannair has received honoraria/speaking/consulting fees from Sanofi, Abbott, Boston Scientific, Biosense Webster, Inc, Zoll Medical Corporation, Pfizer, Inc, and the Academy for Continued Healthcare Learning. Dr DiBiase has received honoraria/speaking/consulting fees from Baylis Medical Company, Biosense Webster, Inc, Abbott, Boston Scientific, Medtronic, Biotronik, Rhythm Management Group Corp, and Zoll Medical Corporation. Dr Al-Ahmad has received honoraria/speaking/consulting fees from Biosense Webster, Inc, Medtronic, Boston Scientific, Abbott, Mediasphere Medical, Medtelligence, and Biosig Technologies. Dr Natale has received honoraria/speaking/consulting fees from Medtronic, Biosense Webster, Inc, Boston Scientific, Abbott, Baylis Medical Company, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Importance: Chlamydia trachomatis ( Ct ) is the most common sexually transmitted bacterium globally. Endocervical and vaginal microbiome interactions are rarely examined within the context of Ct or among vulnerable populations. We evaluated 258 vaginal and 92 paired endocervical samples from Fijian women using metagenomic shotgun sequencing. Over 37% of the microbiomes could not be classified into sub-community state types (subCSTs). We, therefore, developed subCSTs IV-D0, IV-D1, IV-D2, and IV-E-dominated primarily by Gardnerella vaginalis -to improve classification. Among paired microbiomes, the endocervix had a significantly higher alpha diversity and, independently, higher diversity for high-risk human papilloma virus (HPV) genotypes compared to low-risk and no HPV. Ct- infected endocervical networks had smaller clusters without interactions with potentially beneficial Lactobacillus spp. Overall, these data suggest that G. vaginalis may generate polymicrobial biofilms that predispose to and/or promote Ct and possibly HPV persistence and pathogenicity. Our findings expand on the existing repertoire of endocervical and vaginal microbiomes and fill in knowledge gaps regarding Pacific Islanders., Competing Interests: The authors declare no conflict of interest.

Background: Bilateral cardiac sympathetic denervation (BCSD) for refractory life-threatening ventricular arrhythmias is a neuromodulatory intervention targeting sympathetically driven focal or re-entrant ventricular arrhythmias., Objectives: This study sought to provide a more complete and successful option for intervention in patients in whom premature ventricular contraction (PVC) ablation is not feasible or has been unsuccessful., Methods: A total of 43 patients with >5% PVC burden and concomitant nonischemic cardiomyopathy (NICM) who previously failed medical and ablation therapies were referred for BCSD. All patients underwent bilateral video-assisted thoracoscopic surgical approach with T1-T4 sympathectomy. Primary effectiveness endpoints were postprocedural PVC burden resolution, improvement in left ventricular ejection fraction (LVEF), and cessation of antiarrhythmic drugs (AADs). Safety endpoints included peri- and postprocedural complications. Outcomes were assessed over a 1-year follow-up period., Results: Among the 43 patients who underwent BCSD, the mean age was 52.3 ± 14.7 years, 69.8% of whom were male patients. Presenting mean LVEF was 38.7% ± 7.8%, and PVC burden was 23.7% ± 9.9%. There were significant reductions in PVC burden postprocedurally (1.3% ± 1.1% post-BCSD, compared with 23.7% ± 9.9% pre-BCSD, P < 0.001) and improvements in LVEF (46.3% ± 9.5% post-BCSD, compared with 38.7% ± 7.8% pre-BCSD, P < 0.001). The rate of ICD therapies decreased from 81.4% (n = 35) to 11.6% (n = 5) (P < 0.001), leading to a significant reduction in use of AADs (100.0% to 11.6%, P < 0.001) and improvement in mean NYHA functional class (2.5 ± 0.5 to 1.4 ± 0.2, P < 0.001). Major intraoperative complications were seen in 4.7% of patients (hemothorax and chylothorax). Of the patients, 81.4% (n = 35) experienced no mortality or major complications over a 1-year follow-up period, with the remaining still within their first year postprocedure., Conclusions: BCSD is effective for the management of refractory PVCs and ventricular tachycardia who have failed previous ablation therapy., Competing Interests: Funding Support and Author Disclosures Dr Lakkireddy has served as consultant for Abbott, Acutus, AltaThera, Boston Scientific, Biosense Webster, and Medtronic. Dr Pothineni has received speaking honoraria from Boston Scientific. Dr Gopinathannair has served as consultant and has received honoraria from Abbott Medical, and Sanofi; and has served on an advisory board for Pacemate. Dr Natale has served as consultants for Medtronic, Abbott, Biosense Webster, Boston Scientific, and Acutus. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Inpatient initiation of sotalol is recommended owing to its proarrhythmic effects., Objectives: The DASH-AF (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation) trial evaluates the safety and feasibility of intravenous (IV) sotalol, achieving a steady state with maximum QTc prolongation within 6 hours instead of the traditional 5-dose inpatient oral (PO) titration., Methods: DASH-AF is a prospective, nonrandomized, multicenter, open-label trial consisting of patients who underwent IV sotalol loading dose to initiate rapid oral therapy for atrial arrhythmias. IV dose was calculated based on the target oral dose as indicated by baseline QTc and renal function. Patients' QTc (in sinus) was measured via electrocardiography at 15-minute intervals and after IV loading completion. Patients were discharged 4 hours after first oral dose. All patients were monitored via mobile cardiac outpatient telemetry for 72 hours. The control group was composed of patients admitted for the traditional 5 PO doses. Safety outcomes were assessed in both groups., Results: A total of 120 patients from 3 centers were enrolled from 2021 to 2022 in the IV loading group (compared with type of AF- and renal function-matched patients in the conventional PO loading cohort). This study demonstrated no significant change in ΔQTc in both groups, with a significantly lower number of patients requiring dose adjustment in the IV arm compared with the PO arm (4.1% vs 16.6%; P = 0.003). This led to potential cost savings of up to $3,500.68 per admission., Conclusions: The DASH-AF trial shows that rapid IV sotalol loading in atrial fibrillation/flutter patients for rhythm control is feasible and safe compared with conventional oral loading with significant cost reduction. (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation [DASH-AF]; NCT04473807)., Competing Interests: Funding Support and Author Disclosures This study was funded by an unrestricted grant from AltaThera Pharmaceuticals. Special thanks to Philips Biotel for their support with the heart monitors in the study. Dr Lakkireddy is consultant for Abbott, Acutus, AltaThera, Boston Scientific, Biosense Webster, and Medtronic. Dr Pothineni has received speaking honorarium from Boston Scientific. Dr Gopinathannair has received consultancy or honoraria from Abbott Medical, Zoll Medical, and Sanofi; and is on the advisory board for Pacemate. Dr Woun Seo was an employee of AltaThera Pharmaceuticals at the time of this study initiation; and is consultant for AltaThera. Dr Natale is consultant for Medtronic, Abbott, Biosense Webster, Boston Scientific, and Acutus. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Chlamydia trachomatis , a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression., Methods: We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site., Results: The 78 C. trachomatis genomes from participants resolved into two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorectal" clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains., Discussion: The absence of large numbers of fixed SNPs between C. trachomatis genomes within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant genetic variation in different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Joseph, Bommana, Ziklo, Kama, Dean and Read.)

Chlamydia trachomatis is a sexually transmitted pathogen and a global public health concern. Little is known about the microbial composition and function across endocervical, vaginal, and rectal microbiomes in the context of C. trachomatis infection. We evaluated the microbiomes of 10 age-matched high-risk Fijian women with and without C. trachomatis using metagenomic shotgun sequencing (MSS). Lactobacillus iners and Lactobacillus crispatus dominated the vagina and endocervix of uninfected women. Species often found in higher relative abundance in bacterial vaginosis (BV)-Mageeibacillus indolicus, Prevotella spp., Sneathia spp., Gardnerella vaginalis, and Veillonellaceae spp.-were dominant in C. trachomatis-infected women. This combination of BV pathogens was unique to Pacific Islanders compared to previously studied groups. The C. trachomatis-infected endocervix had a higher diversity of microbiota and microbial profiles that were somewhat different from those of the vagina. However, community state type III (CST-III) and CST-IV predominated, reflecting pathogenic microbiota regardless of C. trachomatis infection status. Rectal microbiomes were dominated by Prevotella and Bacteroides , although four women had unique microbiomes with Gardnerella , Akkermansia , Bifidobacterium , and Brachyspira . A high level of microbial similarity across microbiomes in two C. trachomatis-infected women suggested intragenitorectal transmission. A number of metabolic pathways in the endocervix, driven by BV pathogens and C. trachomatis to meet nutritional requirements for survival/growth, 5-fold higher than that in the vagina indicated that endocervical microbial functions are likely more diverse and complex than those in the vagina. Our novel findings provide the impetus for larger prospective studies to interrogate microbial/microbiome interactions that promote C. trachomatis infection and better define the unique genitorectal microbiomes of Pacific Islanders. IMPORTANCE Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections worldwide, with a disturbing increase in annual rates. While there is a plethora of data on healthy and pathogenic vaginal microbiomes-defining microbial profiles and associations with sexually transmitted infections (STIs)-far fewer studies have similarly examined the endocervix or rectum. Further, vulnerable populations, such as Pacific Islanders, remain underrepresented in research. We investigated the microbial composition, structure, and function of these anatomic microbiomes using metagenomic shotgun sequencing among a Fijian cohort. We found, primarily among C. trachomatis-infected women, unique microbial profiles in endocervical, vaginal, and rectal microbiomes with an increased diversity and more complex microbial pathways in endocervical than vaginal microbiomes. Similarities in microbiome composition across sites for some women suggested intragenitorectal transmission. These novel insights into genitorectal microbiomes and their purported function require prospective studies to better define Pacific Islander microbiomes and microbial/microbiome interactions that promote C. trachomatis infection.

Background: Medical treatment of inappropriate sinus tachycardia (IST) remains suboptimal. Radiofrequency sinus node (RF-SN) ablation has poor success and higher complication rates., Objective: We aimed to compare clinical outcomes of the novel SN sparing hybrid ablation technique with those of RF-SN modification for IST management., Methods: This is a multicenter prospective registry comparing the SN sparing hybrid ablation strategy with RF-SN modification. The hybrid procedure was performed using an RF bipolar clamp, isolating superior vena cava/inferior vena cava with the creation of a lateral line across the crista terminalis while sparing the SN region (identified by endocardial 3-dimensional mapping). RF-SN modification was performed by endocardial and/or epicardial mapping and ablation at the site of earliest atrial activation., Results: Of the 100 patients (hybrid ablation group, n = 50; RF-SN group, n = 50), 82% were women, and the mean age was 22.8 years. Normal sinus rhythm and rate were restored in all patients in the hybrid group (vs 84% in the RF-SN group; P = .006). Hybrid ablation was associated with significantly better improvement in mean daily heart rate and peak 6-minute walk heart rate compared with RF-SN ablation. The RF-SN group had a significantly higher rate of redo procedures (100% vs 8%; P < .001), phrenic nerve injury (14% vs 0%; P = .012), lower acute pericarditis (48% vs 92%; P < .0001), permanent pacemaker implantation (50% vs 4%; P < .0001) than did the hybrid ablation group., Conclusion: The novel sinus node sparing hybrid ablation procedure appears to be more efficacious and safer in patients with symptomatic drug-resistant IST with long-term durability than RF-SN ablation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The STROKE-VT (Safety and Efficacy of Direct Oral Anticoagulant Versus Aspirin for Reduction of Risk of Cerebrovascular Events in Patients Undergoing Ventricular Tachycardia Ablation) study is a multicenter, randomized controlled trial that examined the differences in cerebrovascular events between direct oral anticoagulant (DOAC) and aspirin (ASA) use postprocedurally in patients who underwent left ventricular arrhythmia (LVA) ablation (ventricular tachycardia [VT] or premature ventricular contraction [PVC]) using radiofrequency ablation (RFA)., Background: There exists limited data regarding antiplatelet or anticoagulation strategy following LVA ablation., Methods: A total of 246 patients scheduled for LVA-RFA were randomized 1:1 postprocedurally to receive DOACs or ASA. The study's primary endpoint was the incidence of stroke or transient ischemic attack (TIA) or asymptomatic cerebrovascular events (ACEs) detected by magnetic resonance imaging at 24 hours and 30 days of follow-up. The secondary endpoints included procedure-related complications (composite of any vascular complication, pericardial complication, heart block, and thromboembolic event, excluding stroke or TIA) and in-hospital mortality., Results: There were no differences between groups regarding baseline and ablation characteristics (except the percentage of patients who underwent VT ablation, rate of amiodarone use, and total RFA time). Postprocedure cerebrovascular events (stroke and TIA) were lower in the DOAC arm versus the ASA arm (0% vs 6.5%; P < 0.001 and 4.9% vs. 18%; P < 0.001, respectively). Patients in the ASA group had more MRI-detected ACEs compared with the DOAC group both at 24-hour (23% vs 12%; P = 0.03) and 30-day (18% vs 6.5%; P = 0.006) follow-up. Acute procedure-related complications and in-hospital mortality were similar between the 2 groups., Conclusions: DOAC use following endocardial and/or epicardial ablation for LVA-RFA was associated with reduced risk of TIA or stroke and asymptomatic MRI-detected cerebrovascular events., Competing Interests: Funding Support and Author Disclosures Dr Lakkireddy has been a consultant for Abbott, Biosense Webster, Boston Scientific, Phillips, Stereotaxis, and Atricure Inc. Dr Gopinathannair has been a consultant for and has received honoraria from Abbott Medical, Biotronik, Boston Scientific, Pfizer, and Zoll Medical; and has been a physician advisor (no compensation) for HealthTrust PG, Altathera, and PaceMate. Dr Natale has been a consultant for Abbott, Biosense Webster, Boston Scientific, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Chlamydiaceae are a family of obligate intracellular, gram-negative bacteria known to readily exchange DNA by homologous recombination upon co-culture in vitro , allowing the transfer of antibiotic resistance residing on the chlamydial chromosome. Among all the obligate intracellular bacteria, only Chlamydia ( C .) suis naturally integrated a tetracycline resistance gene into its chromosome. Therefore, in order to further investigate the readiness of Chlamydia to exchange DNA and especially antibiotic resistance, C. suis is an excellent model to advance existing co-culture protocols allowing the identification of factors crucial to promote homologous recombination in vitro . With this strategy, we co-cultured tetracycline-resistant with rifamycin group-resistant C. suis , which resulted in an allover recombination efficiency of 28%. We found that simultaneous selection is crucial to increase the number of recombinants, that sub-inhibitory concentrations of tetracycline inhibit rather than promote the selection of double-resistant recombinants, and identified a recombination-deficient C. suis field isolate, strain SWA-110 (1-28b). While tetracycline resistance was detected in field isolates, rifampicin/rifamycin resistance (RifR) had to be induced in vitro . Here, we describe the protocol with which RifR C. suis strains were generated and confirmed. Subsequent whole-genome sequencing then revealed that G530E and D461A mutations in rpoB , a gene encoding for the β-subunit of the bacterial RNA polymerase (RNAP), was likely responsible for rifampicin and rifamycin resistance, respectively. Finally, whole-genome sequencing of recombinants obtained by co-culture revealed that recombinants picked from the same plate may be sibling clones and confirmed C. suis genome plasticity by revealing variable, apparently non-specific areas of recombination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Marti, Bommana, Read, Pesch, Prähauser, Dean and Borel.)

The obligate intracellular pathogen Chlamydia trachomatis ( Ct ) is the leading cause of bacterial sexually transmitted infections and blindness globally. To date, Ct urogenital strains are considered tryptophan prototrophs, utilizing indole for tryptophan synthesis within a closed-conformation tetramer comprised of two α (TrpA)- and two β (TrpB)-subunits. In contrast, ocular strains are auxotrophs due to mutations in TrpA, relying on host tryptophan pools for survival. It has been speculated that there is strong selective pressure for urogenital strains to maintain a functional operon. Here, we performed genetic, phylogenetic, and novel functional modeling analyses of 595 geographically diverse Ct ocular, urethral, vaginal, and rectal strains with complete operon sequences. We found that ocular and urogenital, but not lymphogranuloma venereum, TrpA-coding sequences were under positive selection. However, vaginal and urethral strains exhibited greater nucleotide diversity and a higher ratio of nonsynonymous to synonymous substitutions [Pi(a)/Pi(s)] than ocular strains, suggesting a more rapid evolution of beneficial mutations. We also identified nonsynonymous amino acid changes for an ocular isolate with a urogenital backbone in the intergenic region between TrpR and TrpB at the exact binding site for YtgR-the only known iron-dependent transcription factor in Chlamydia -indicating that selective pressure has disabled the response to fluctuating iron levels. In silico effects on protein stability, ligand-binding affinity, and tryptophan repressor (TrpR) affinity for single-stranded DNA (ssDNA) measured by calculating free energy changes (ΔΔ G ) between Ct reference and mutant tryptophan operon proteins were also analyzed. We found that tryptophan synthase function was likely suboptimal compared to other bacterial tryptophan prototrophs and that a diversity of urogenital strain mutations rendered the synthase nonfunctional or inefficient. The novel mutations identified here affected active sites in an orthosteric manner but also hindered α- and β-subunit allosteric interactions from distant sites, reducing efficiency of the tryptophan synthase. Importantly, strains with mutant proteins were inclined toward energy conservation by exhibiting an altered affinity for their respective ligands compared to reference strains, indicating greater fitness. This is not surprising as l-tryptophan is one of the most energetically costly amino acids to synthesize. Mutations in the tryptophan repressor gene ( trp R) among urogenital strains were similarly detrimental to function. Our findings indicate that urogenital strains are evolving more rapidly than previously recognized with mutations that impact tryptophan operon function in a manner that is energetically beneficial, providing a novel host-pathogen evolutionary mechanism for intracellular survival. IMPORTANCE Chlamydia trachomatis ( Ct ) is a major global public health concern causing sexually transmitted and ocular infections affecting over 130 million and 260 million people, respectively. Sequelae include infertility, preterm birth, ectopic pregnancy, and blindness. Ct relies on available host tryptophan pools and/or substrates to synthesize tryptophan to survive. Urogenital strains synthesize tryptophan from indole using their intact tryptophan synthase (TS). Ocular strains contain a trp A frameshift mutation that encodes a truncated TrpA with loss of TS function. We found that TS function is likely suboptimal compared to other tryptophan prototrophs and that urogenital stains contain diverse mutations that render TS nonfunctional/inefficient, evolve more rapidly than previously recognized, and impact operon function in a manner that is energetically beneficial, providing an alternative host-pathogen evolutionary mechanism for intracellular survival. Our research has broad scientific appeal since our approach can be applied to other bacteria that may explain evolution/survival in host-pathogen interactions., (Copyright © 2021 Bommana et al.)

Background: Smartphone technologies have been recently developed to assess heart rate and rhythm, but their role in accurately detecting atrial fibrillation (AF) remains unknown., Objective: We sought to perform a meta-analysis using prospective studies comparing Smartwatch technology with current monitoring standards for AF detection (ECG, Holter, Patch Monitor, ILR)., Methods: We performed a comprehensive literature search for prospective studies comparing Smartwatch technology simultaneously with current monitoring standards (ECG, Holter, and Patch monitor) for AF detection since inception to November 25th, 2019. The outcome studied was the accuracy of AF detection. Accuracy was determined with concomitant usage of ECG monitoring, Holter monitoring, loop recorder, or patch monitoring., Results: A total of 9 observational studies were included comparing smartwatch technology, 3 using single-lead ECG monitoring, and six studies using photoplethysmography with routine AF monitoring strategies. A total of 1559 patients were enrolled (mean age 63.5 years, 39.5% had an AF history). The mean monitoring time was 75.6 days. Smartwatch was non-inferior to composite ECG monitoring strategies (OR 1.06, 95% CI 0.93 - 1.21, p=0.37), composite 12 lead ECG/Holter monitoring (OR 0.90, 95% CI 0.62 - 1.30, p=0.57) and patch monitoring (OR 1.28, 95% CI 0.84 - 1.94, p=0.24) for AF detection. The sensitivity and specificity for AF detection using a smartwatch was 95% and 94%, respectively., Conclusions: Smartwatch based single-lead ECG and photoplethysmography appear to be reasonable alternatives for AF monitoring.

Purpose: Use of oral anticoagulation (OAC) in patients with a history of intracranial hemorrhage (ICH) is often considered high risk as OAC-related ICH is associated with high mortality rates. Left atrial appendage closure with a WATCHMAN device is an alternative management strategy to OAC to decrease thrombotic risk in atrial fibrillation patients; however use of OAC followed by dual antiplatelet therapy (DAPT) or DAPT therapy alone is required for 6 months post-procedurally. In this study, we examined the safety of WATCHMAN implantation followed by 6 months of anti-thrombotic therapy in patients with a history of ICH., Methods: This is a retrospective analysis of 63 patients with a history of ICH prior to WATCHMAN implantation (Group I) and 95 patients without a history of ICH who underwent WATCHMAN placement (Group II). The primary outcome was death, stroke, or major bleeding within 6 months of WATCHMAN placement., Results: The average CHA 2 DS 2 -VASc of Group I was 4.9 ± 1.7 vs 4.7 ± 1.4 for Group II (p = 0.34). The most common type of ICH in Group I was an intracerebral hemorrhage (57%). The median time between ICH and WATCHMAN implantation in Group I patients was 212 days. A total of 19% of Group I patients were managed with DAPT alone post-procedurally vs. 3% in Group II (p < 0.001). Similar to 89% of Group II (p = 0.19), 95% of Group I patients were free of the primary outcome at 6 months. No Group I patients had recurrent ICH within 6 months after WATCHMAN implantation., Conclusion: In a retrospective, multicenter series of patients with a history of ICH prior to WATCHMAN implantation, WATCHMAN placement was performed safely with 6-month outcomes that were similar to patients without a history of ICH, encompassing the time during which a patient with a history of ICH would need antithrombotic therapy to facilitate WATCHMAN placement.

Introduction: Prospective studies on rivaroxaban and apixaban have shown the safety and efficacy of direct anticoagulation agents (DOAC)s used peri-procedurally during radiofrequency ablation (RFA) of atrial fibrillation (AF). Studies comparing the two agents have not been performed., Methods: Consecutive patients from a prospective registry who underwent RFA of AF between April 2012 and March 2015 and were on apixaban or rivaroxaban were studied. Clinical variables and outcomes were noted., Results: There were a total of 358 patients (n = 56 on apixaban and n = 302 on rivaroxaban). There were no differences in baseline characteristics between both groups. The last dose of rivaroxaban was administered the night before the procedure in 96% of patients. In patients on apixaban, 48% of patients whose procedure was in the afternoon took the medication on the morning of the procedure. TIA/CVA occurred in 2 patients (0.6%) in rivaroxaban group with none in apixaban group (p = 0.4). There was no difference in the rate of pericardial effusion between apixaban and rivaroxaban groups [1.7% vs 0.6% (p = 0.4)]. Five percent of patients in both groups had groin complications (p = 0.9). In apixaban group, all groin complications were small hematomas except one patient who had a pseudoaneurysm (1.6%). One pseudo-aneurysm, 1 fistula and 3 large hematomas were noted in patients on rivaroxaban (1.7%) with the rest being small hematomas. DOACs were restarted post procedure typically 4 h post hemostasis., Conclusions: Peri-procedural uninterrupted use of apixaban and rivaroxaban during AF RFA is safe and there are no major differences between both groups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lakkireddy receives speaker honoraria from St. Jude Medical, Boehringer Ingelheim, Jansen, and Bristol Meyers Squibb., (Copyright © 2020 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Single-chamber leadless pacemakers (LPs) have been shown to be an effective alternative to conventional transvenous pacemakers (CTPs), but their benefit in the context of cardioinhibitory vasovagal syncope (CI-VVS) is unknown., Objective: The purpose of this study was to evaluate the safety and efficacy of LP compared with dual-chamber CTP for CI-VVS., Methods: We conducted a multicenter, retrospective study comparing patients who received LP or dual-chamber CTP for drug-refractory CI-VVS. CI-VVS was diagnosed clinically and supported by cardiac monitoring and head-up tilt table testing. The primary efficacy endpoint was freedom from syncope during follow-up. Secondary endpoints included device efficacy and safety estimated by device-related major and minor adverse events (AEs)., Results: Seventy-two patients (24 LP, 48 CTP; age 32 ± 5.5 years; 90% female; syncope frequency 7.6 ± 3.4 per year) were included. At 1 year, 91% of patients (22/24) in the LP group and 94% of patients (43/48) in the CTP group met the primary efficacy endpoint (P = .7). Device efficacy endpoint was met in 92% of the LP group and 98% of the CTP group (P = .2). Early major AEs occurred in 2 of 24 in the LP group and 3 of 48 in the CTP group (P = .4). Late major AEs occurred in 0 of 24 in the LP group and 2 of 48 in the CTP group (P = 1)., Conclusion: In patients with CI-VVS, single-chamber LP demonstrated equivalent efficacy in reducing syncopal events compared to dual-chamber CTP, with a similar safety profile., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Warfarin is deemed safe compared to bridging with heparin in the peri-procedure setting while implanting cardiac devices. The timing of discontinuation and re-initiation of direct anticoagulant agents (DOACs) such as dabigatran, apixaban, and rivaroxaban in the peri-procedural setting in comparison to warfarin is not well studied., Objective: We wanted to compare three DOAC agents with warfarin during cardiac device implantation., Methods: Consecutive patients on treatment with dabigatran, rivaroxaban, or apixaban (group A) undergoing a cardiac device generator change, upgrade, or new implantation procedure were compared to those on warfarin (group B). Incidence of hematoma, infection, effusion, stroke, and other complications were noted at 1 day, 1 week, and 3 months., Results: A total of 311 patients in group A underwent the above procedures with 73 patients on dabigatran, 153 on rivaroxaban, and 85 on apixaban. There were 467 patients on warfarin in group B. Mean age of the total population was 68 ± 12 years with 67% males and > 80% Caucasians. The last dose of the DOAC was the night prior to the procedure and resumed the night of the procedure (single dose interruption for apixaban and dabigatran and no un-interruption for rivaroxaban). There was no difference noted in the incidence of minor or major hematoma (9% vs 8.5%, p = 0.7). No stroke occurred in either group., Conclusion: Use of DOAC agents with transient interruption of one dose is as safe as warfarin in the peri-procedural setting during implantation of cardiac devices.

Background: Electrical isolation of the left atrial appendage (LAA) may provide incremental benefits for arrhythmia management in patients undergoing radiofrequency ablation (RFA) for persistent atrial fibrillation (AF)., Objective: The aim of this study was to compare efficacy and safety of endocardial ablation and LAA exclusion with LARIAT device for electrical and mechanical exclusion of LAA., Methods: We compared patients who underwent endocardial LAA isolation during index RFA for persistent AF and underwent a repeat RFA to patients who underwent LAA exclusion with LARIAT device followed by RFA for AF in this multicenter registry. Efficacy of electrical and mechanical isolation of LAA was assessed., Results: We included 182 patients of which 91 patients underwent endocardial LAA isolation during RFA for AF, and 91 patients underwent LAA exclusion with LARIAT device followed by RFA for AF. Baseline characteristics were similar except for higher CHA 2 DS 2- VASc score, coronary artery disease, and prior stroke rate in LARIAT arm. Persistence of electrical isolation (measured at beginning of second procedure) after LARIAT procedure was higher than one-time AF-RFA (96.7% vs 52.8%, p < 0.01). Acute pulmonary vein isolation rates were similar in both arms. AF recurrence rate after second isolation attempts at 1 year was similar in both arms. No difference in major complications was noted between both arms., Conclusions: LAA exclusion with LARIAT device appears to be more efficacious as compared to one-time endocardial ablation, but not compared to repeat isolation, in achieving complete electrical isolation of LAA for persistent AF.

Background: Premature ventricular contractions are a common clinical presentation that drives further diagnostic workup. We hypothesize the presence of underlying inflammation is often unrecognized in these patients with a potential for continued disease progression if not diagnosed and treated early in the disease course., Methods: This is a single-center, prospective study including 107 patients with frequent symptomatic premature ventricular contractions (>5000/24 h) and no known ischemic heart disease. Patients underwent a combination of laboratory testing, 18F-fluorodeoxyglucose positron emission tomography scan, cardiac magnetic resonance imaging, and biopsy. Patients were diagnosed with myocarditis based on a multidisciplinary approach and treated with immunosuppressive therapy., Results: The mean age of the cohort was 57±15 years, 41% were males, and left ventricular ejection fraction was 47±11.8%. Positive positron emission tomography scan was seen in 51% (55/107), of which 51% (28/55) had preserved left ventricle function. Based on clinical profile, 18F-fluorodeoxyglucose-positron emission tomography imaging, cardiac magnetic resonance, and histological data 58% patients (32/55) received immunosuppressive therapy alone and 25.4% (14/55) received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% (31/46) over a mean follow-up of 6±3 months. In patients with left ventricle systolic dysfunction, 37% (10/27) showed an improvement in mean left ventricular ejection fraction of 13±6%., Conclusions: Approximately 51% of patients presenting with frequent premature ventricular contractions have underlying myocardial inflammation in this cohort. 18F-fluorodeoxyglucose-positron emission tomography scan can be a useful modality for early diagnosis and treatment with immunosuppressive therapy in selected patients can improve clinical outcomes.

Endocardial LAAO has been increasingly utilized in atrial fibrillation (AF) patients who are not suitable for long term oral anticoagulation. While overall procedural complications have decreased, rare complications like contiguous vessel and valve injury may be more frequently seen in the future with increase in the procedure volume. We performed a systematic search using predefined terms which reviewed all cases published in literature of contiguous vessel (pulmonary artery, pulmonary vein and left circumflex artery) and mitral valve injury caused by LAAO devices. Our results showed that Amplatzer Cardiac Plug (ACP) and Amplatzer Amulet devices were the most commonly used devices. Pulmonary artery perforation was the most commonly seen collateral vessel injury associated with LAAO. Close proximity of left atrial appendage to pulmonary artery was noted in all cases of pulmonary artery injury. Pulmonary artery injury commonly manifests as pericardial tamponade with hemodynamic collapse and is often fatal. Most common denominator of all the reviewed cases was the presence of an oversized LAAO device. In conclusion, collateral vessels and valve injury can be seen after LAAO mostly with double lobe devices such as ACP or Amulet. Increased awareness by the operators along with proper imaging and investigations could potentially mitigate such rare complications associated with LAAO.

Background: Dofetilide is a class III antiarrhythmic drug commonly used for treatment of atrial fibrillation. Drug guidelines mandate a 3-month waiting period before initiating dofetilide after amiodarone use. Whether patients with an implantable cardioverter-defibrillator (ICD) can be rapidly switched from amiodarone to dofetilide is not known., Objective: The purpose of this study was to evaluate whether rapid switching from amiodarone to dofetilide is safe in atrial fibrillation patients with an ICD., Methods: In this retrospective observational study, we assessed the feasibility and the short- and long-term safety of rapid switching from amiodarone to dofetilide in hospitalized atrial fibrillation with an ICD., Results: The study included a total of 179 patients who were followed for 12.6 ± 2.2 months. All patients had drug initiation during hospitalization. Dofetilide resulted in successful cardioversion in 66% (118/179). Twenty percent of patients (36/179) required dofetilide dose adjustments in the initiation phase because of QT prolongation and decreased creatinine clearance. A total of 6.1% of patients (11/179) required drug discontinuation. The incidence of torsades de pointes was 1.1% (2/179) during initiation. One patient (0.5%) had self-terminating ventricular tachycardia at follow-up. No other significant adverse events were noted during follow-up., Conclusion: Atrial fibrillation patients with an ICD can be rapidly switched to dofetilide after 7 days of discontinuation of amiodarone without significant arrhythmia-related complications. Prospective studies with large sample sizes, especially of women, should be performed to further validate these findings., (Copyright © 2019. Published by Elsevier Inc.)

Chlamydiae are globally widespread obligate intracellular bacteria, which several species are a well-recognized threat to human and animal health. In Australia, the most successful chlamydial species are the infamous koala pathogen C. pecorum, and C. psittaci, an emerging pathogen associated with zoonotic events. Little is known about infections caused by other chlamydial organisms in Australian livestock or wildlife. Considering that these hosts can be encountered by humans at the animal/human interface, in this study, we investigated genetic diversity of chlamydial organisms infecting Australian domesticated and wild ungulates. A total of 185 samples from 129 domesticated (cattle, horses, sheep, and pigs) and 29 wild (deer) ungulate hosts were screened with C. pecorum and C. psittaci species-specific assays, followed by a screen with pan-Chlamydiales assay. Overall, chlamydial DNA was detected in 120/185 (65%) samples, including all ungulate hosts. Species-specific assays further revealed that C. pecorum and C. psittaci DNA were detected in 27% (50/185) and 6% (11/185) of the samples, respectively, however from domesticated hosts only. A total of 46 "signature" 16S rRNA sequences were successfully resolved by sequencing and were used for phylogenetic analyses. Sequence analyses revealed that genetically diverse novel as well as traditional chlamydial organisms infect an expanded range of ungulate hosts in Australia. Detection of the C. psittaci and C. pecorum in livestock, and novel taxa infecting horses and deer raises questions about the genetic make-up and pathogenic potential of these organisms, but also concerns about risks of spill-over between livestock, humans, and native wildlife., (© 2019 Blackwell Verlag GmbH.)

Chlamydia pecorum and Chlamydia abortus are related ruminant pathogens endemic to different global regions. Potential co-infections combined with the lack of species-specific serological assays challenge accurate diagnosis. Serological screening revealed low C. abortus seropositivity with the peptide-based ELISA (1/84; 1.2%) in Australian sheep yet moderate seropositivity in a Swiss flock with history of C. abortus-associated abortions (17/63; 26.9%). By whole cell antigen complement fixation tests (CFT) and ELISA, chlamydial seropositivity was significantly higher in all groups, suggesting cross-reactivity between these two chlamydial species and non-specificity of the tests. However, only C. pecorum DNA could be detected by qPCR in Chlamydia seropositive Australian animals screened, suggesting chlamydial seropositivity was due to cross-reactivity with endemic C. pecorum infections. These results suggest ascribing Chlamydia seropositivity to chlamydial species in livestock using whole-cell antigen CFT or ELISA should be treated with caution; and that peptide-based ELISA and qPCR provide greater chlamydial species-specificity.

Chlamydia are a genus of successful obligate intracellular pathogens spread across humans, wildlife, and domesticated animals. The most common species reported in livestock in this genus are Chlamydia abortus , Chlamydia psittaci , Chlamydia suis , and Chlamydia pecorum . Chlamydial infections trigger a series of inflammatory disease-related sequelae including arthritis, conjunctivitis, pneumonia, and abortion. Other bacteria in the phylum Chlamydiae have also been reported in livestock and wildlife but their impact on animal health is less clear. Control of chlamydial infections relies on the use of macrolides, fluoroquinolones, and tetracyclines. Tetracycline resistance (TET R ) reported for porcine C. suis strains in association with the use of tetracycline feed is a potentially significant concern given experimental evidence highlighting that the genetic elements inferring TET R may be horizontally transferred to other chlamydial species. As documented in human Chlamydia trachomatis infections, relapse of infections, bacterial shedding post-antibiotic treatment, and disease progression despite chlamydial clearance in animals have also been reported. The identification of novel chlamydiae as well as new animal hosts for previously described chlamydial pathogens should place a renewed emphasis on basic in vivo studies to demonstrate the efficacy of existing and new antimicrobial treatment regimes. Building on recent reviews of antimicrobials limited to C. trachomatis and C. suis , this review will explore the use of antimicrobials, the evidence and factors that influence the treatment failure of chlamydial infections in animals and the future directions in the control of these important veterinary pathogens.

Background: Percutaneous left atrial appendage exclusion (LAAE) has evolved as an alternative strategy for stroke prevention in atrial fibrillation (AF). Recent observational data have suggested that epicardial LAAE can have substantial impact on arrhythmia burden and hemodynamic profile., Objectives: The authors aimed to study the impact of epicardial versus endocardial LAAE on systemic blood pressure in hypertensive AF patients., Methods: This was a prospective, nonrandomized study comparing 247 patients who underwent epicardial LAAE with 124 patients with endocardial exclusion. Clinical outcomes were measured at 3 months and 1 year. Primary outcome was improvement in systolic blood pressure (SBP) between both groups compared with baseline. Secondary outcome included changes in diastolic pressures (DBP), serum electrolytes, and creatinine., Results: There was no significant difference in baseline SBP between epicardial and endocardial groups. SBP was significantly lower in the epicardial group both at 3 months (122 ± 11.8 mm Hg vs. 129.7 ± 8.2 mm Hg; p < 0.001) and 1 year (123 ± 11.6 mm Hg vs. 132.2 ± 8.8 mm Hg; p < 0.001) compared with the endocardial group. An adjusted multivariate linear mixed effects model demonstrated that epicardial LAAE significantly decreased SBP by 7.4 mm Hg at 3 months and by 8.9 mm Hg at 1 year (p < 0.0001). There was a trend toward lower DBP with epicardial LAAE at 3 months by 1.3 mm Hg (p = 0.2) and at 1 year by 1.8 mm Hg (p = 0.09). There was no significant difference in serum electrolytes and creatinine between both groups., Conclusions: In hypertensive AF patients, epicardial LAAE significantly decreases SBP both at 3 and 12 months compared with endocardial exclusion., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is limited data regarding effect of prolonged radiation exposure during electrophysiological (EP) procedures on direct DNA damage. Comet test has shown to assess DNA damage following radiation exposure., Methods: We performed a single-center prospective observational study assessing direct DNA damage using the quantitative comet assay in patients undergoing cardiac resynchronization (CRT) and atrial fibrillation (AF) catheter ablation procedures. Venous comet assay was performed pre, immediately post procedure and at 3-month duration in twenty-two (N=22) patients who underwent catheter ablation for symptomatic AF and fourteen (N=14) patients who underwent CRT implantation., Results: The median [interquartile range (IQR)] fluoroscopy time, radiation dose and dose area product (DAP) were 34.3 (27.97 - 45.48) minutes, 853.07 (611.36 - 1334.76) mGy and 16,994.10 (9,023.65 - 58,845.00) UGym2 in the ablation group and 30.05 (18.75 - 37.33) minutes, 345.00 (165.09 - 924.79) mGy and 11,837.20 [7182.67 - 35567.75] UGym2 in the CRT group. When compared with pre-procedure, there was a statistically significant increase in median (IQR) DNA migration on comet assay in the ablation group immediately post procedure [+6.55 µm (0.78, 10.25, p=0.02)] that subsequently decreased at 3 months [-1.00 µm (-2.20, 0.78), p=0.03] but not in the CRT group., Conclusion: There was a significant increase in DNA damage as detected by comet assay immediately post procedure that normalized at 3 months in patients undergoing AF ablation. Further large prospective studies are warranted to evaluate the impact of this prolonged radiation exposure and DNA damage on long-term follow up.

Background: Left atrial (LA) strain (ε) and ε rate (SR) analysis by 2-dimensional speckle tracking echocardiography is a novel method for functional assessment of the LA., Objective: The purpose of this study was to determine the impact of left atrial appendage (LAA) exclusion by Lariat epicardial ligation on mechanical function of the LA by performing ε and SR analysis before and after the procedure., Methods: A total of 66 patients who underwent successful LAA exclusion were included in the study. Of these 66 patients, 32 had adequate paired data for ε and SR analysis. SR during ventricular systole (LA-SRs) represents LA reservoir function, and SR during early ventricular diastole (LA-SRe) represents LA conduit function. ε and SR were determined from apical 4- and 2-chamber views using the electrocardiographic QRS as a reference point. LA volume index as surrogate for LA remodeling was measured from apical views., Results: Mean patient age was 70 ± 9.2 years. LAA ligation resulted in improved reservoir function (LA-SRs: pre 0.72, confidence interval [CI] 0.63-0.83 vs post 0.81, CI 0.73-0.98; P = .043) and conduit function (LA-SRe: pre 0.74, CI 0.67-0.99 vs post 0.89, CI 0.82-1.07; P = .025). LA volume index improved significantly with the Lariat (pre 35.4, CI 29.4-37.2 vs post 29.2, CI 28.2-35.9; P <.023)., Conclusion: LAA exclusion seems to improve mechanical function of the LA and results in reverse LA remodeling., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrioventricular node (AVN) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LPs) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTPs)., Objectives: The purpose of this study was to compare the feasibility and safety of LP with those of single-chamber CTP in patients with AF undergoing AVN ablation., Methods: We conducted a multicenter observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs single-chamber CTP) between February 1, 2014 and November 15, 2016. The primary efficacy end points were acceptable sensing (R wave amplitude ≥5.0 mV) and pacing thresholds (≤2.0 V at 0.4 ms) at follow-up. Safety end points included device-related major and minor (early <1 month, late >1 month) adverse events., Results: A total of 127 patients with LP (n = 60) and CTP (n = 67) were studied. The median follow-up was 12 months (interquartile range 12-18 months). Ninety-five percent of the LP group and 97% of the CTP group met the primary efficacy end point at follow-up (57 of 60 vs 65 of 67; P = .66). There was 1 major adverse event (loss of pacing and sensing) in the LP group and 2 (lead dislodgement) in the CTP group (1 of 60 vs 2 of 67; P = 1.00). There were 6 minor adverse events (5 early and 1 late) in the LP group and 3 (early) in the CTP group (6 of 60 vs 3 of 67; P = .30)., Conclusion: Our results demonstrate the feasibility and safety of LP compared with CTP in patients undergoing AVN ablation for AF., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Lamydia pecorum is a globally recognised livestock pathogen that is capable of causing severe and economically significant diseases such as arthritis in sheep and cattle. Relatively little information is available on the clinical progression of disease and the long-term effects of asymptomatic and symptomatic chlamydiosis in sheep. Recent studies in calves indicate that endemic C. pecorum infections may reduce growth rates. To investigate the clinical health parameters and production impacts of endemic C. pecorum infection in an Australian commercial lamb flock, we performed bimonthly sampling and clinical health assessments on 105 Border Leicester lambs from two to ten months of age. Chlamydial status was investigated via serology and species-specific quantitative PCR. Throughout the study period, conjunctivitis remained a persistent clinical feature while signs of arthritis (e.g. palpable synovial joint effusions) resolved in a subset of lambs while persisting in others. Clinical disease and C. pecorum infection were highest at six months of age (weaning). As previously reported, peak seroconversion tends to occur two months after the onset of clinical symptoms (6 months of age), with lambs clearing chlamydial infection by 10 months of age, despite ongoing disease still being present at this time. Notably, the presence of chlamydial infection did not affect lamb mass or growth rates throughout the study. At necropsy, C. pecorum was not detected within the joints of lambs with chronic arthritis. Molecular analysis of the strains in this flock suggest that the infecting strains circulating in this flock are clonal C. pecorum pathotypes, denoted ST 23, commonly associated with conjunctivitis and polyarthritis in Australian sheep. This study provides a platform for further research in the epidemiology and disease transmission dynamics of C. pecorum infections in sheep., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Chlamydia pecorum is a globally significant livestock pathogen causing pathology and production losses. The on-farm infection and serological dynamics and the relevance of existing diagnostic tools for diagnosing C. pecorum in livestock remains poorly characterized. In this study, we characterized the antigen and antibody dynamics of this pathogen in a longitudinal study of prime lamb production, utilizing the infection focused C. pecorum -specific 16S rRNA qPCR assay and serology based chlamydial Complement fixation Test (CFT)., Methods: The study consisted of 76 Border Leicester mixed sex lambs (39 females and 37 males) that were sampled bimonthly from 2-10 months of age in a commercial farm operating in Central NSW, Australia. Blood/plasma was analysed for CFT antibodies, and swabs from conjunctival, rectal and vaginal sites were analysed for C. pecorum shedding using qPCR. We assessed the temporal and overall dynamics of C. pecorum in lambs, including detailed description and comparison of qPCR and CFT, the timing of first detection by either diagnostic method, the lag between infection and antibody response; and the distribution of qPCR load and CFT antibody titre over time., Results: Over the study period, C. pecorum was highly prevalent (71.0% by qPCR, 92.1% by CFT, 96.0% by both), with 21.1% (16/76) lambs shedding ≥1, 000 qPCR copies/µl (denoted as high shedders). C. pecorum shedding (as evidence of infection) were first observed at two months of age (14.4%) with a significant peak of infection occurring at six months of age (34.2%), whereas seroconversions peaked at eight months of age (81.5%). 52.6% of C. pecorum qPCR and CFT positive lambs became qPCR negative by 10 months of age, indicating clearance of chlamydial infection. Although CFT is utilised for on-farm detection of active infection, we confirm that it lagged behind qPCR detection (average lag 1.7 ± 2.1 months) and that the proportion of qPCR positives simultaneously identified by CFT was low with 2/11 (18.1%), 0/13, 17/25 (68.0%), 5/7 (71.4%) and 1/10 (10.0%) concurrent seroconversions occurring at two, four, six, eight and 10 months of age, respectively., Discussion: This work reveals rapid rates of C. pecorum infection and widespread exposure during lamb production. The comparison of molecular and serological diagnostic agreement longitudinally, supports the use of qPCR as an important ancillary tool for the detection of active infections in conjunction with chlamydial CFT for routine veterinary diagnostics. Development of rapid Point-of-Care (POC) tools for diagnosing active infection would be valuable for producers and veterinarians., Competing Interests: The authors declare there are no competing interests.

Background: We sought to investigate and compare the safety and efficacy of two commonly used antiarrhythmic drugs, Dofetilide (DF) and Sotalol (SL), during inpatient drug initiation in patients with symptomatic atrial fibrillation (AF)., Methods: We performed a single center retrospective study of consecutive patients, admitted for initiation of either DF or SL, for AF between 2012 and 2015. Rates of successful cardioversion, QT interval prolongation, adverse events and drug discontinuations were calculated and compared. A two-tailed p value less than 0.05 was considered statistically significant., Results: Of 378 patients, 298 (78.8%) received DF and 80 (21.2%) SL, mean age was 64 ± 11 years, 90% were Caucasians and 66% were males. Among the patients who remained in AF upon admission (DF: 215/298 (72%) vs. SL: 48/80 (60%)), no significant differences were noted in pharmacological cardioversion rates (DF: 125/215(58%) vs. SL: 30/48 (62.5%); p = 0.58). Baseline QTc was similar between the groups, with higher dose dependent QTc prolongation with DF (472.25± 31.3 vs. 458± 27.03; p = 0.008). There were no significant differences in the rates of adverse events such as bradycardia (7.4% vs. 11.3%; p = 0.26), Torsades de pointes (1.3% vs. 1.2%; p = 1.00), and drug discontinuation (9.0% vs. 5.0%; p = 0.47) between the two groups.

Objectives: The present study describes the use of octreotide (OCT) in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC) who have gastrointestinal (GI) bleeding related to arteriovenous malformations (AVMs), as well as its effect on OAC tolerance and subsequent rebleeding., Background: AVMs cause significant GI bleeding, especially in patients with AF who are receiving OAC for stroke prevention. OCT has been shown to minimize recurrent GI bleeds related to AVMs., Methods: In a multicenter, observational study, 38 AF patients with contraindications to OAC because of AVM-related GI bleeding were started on 100 μg of subcutaneous OCT twice daily. OAC was resumed in all patients within 48 h. Incidence of recurrent GI bleeds was calculated, and hemoglobin levels were recorded at enrollment and at 3 and 6 months' follow-up., Results: After a median follow-up of 8 months, 36 patients (mean age 69 ± 8.0 years; mean CHA 2 DS 2 -VASc score 3 ± 1 and mean HAS-BLED score 3 ± 1) were available for analysis. All were able to successfully resume OAC, and 28 of 36 (78%) remained on OAC at the conclusion of the study, whereas 8 underwent left atrial appendage closure with subsequent OAC discontinuation. No systemic thromboembolic events occurred in follow-up. Of the 28 patients who continued receiving OAC, 19 (68%) were free of recurrent GI bleed, 4 had minor GI bleeds, 4 required transfusion, and 1 required colectomy for GI bleeding. Mean hemoglobin levels in all patients receiving OAC were significantly higher at 3- and 6-month follow-up than at baseline (p < 0.001)., Conclusions: Subcutaneous OCT therapy is an attractive option in AF patients receiving OAC who have AVM-related GI bleeds. It allows successful reinitiation of OAC as a bridge to left atrial appendage exclusion or short-term relief from bleeding., (Copyright © 2017. Published by Elsevier Inc.)

Chlamydia pecorum is a globally recognised livestock pathogen due to the significant clinical and economic impact it poses to livestock producers. Routine serological diagnosis is through a complement fixation test (CFT), which is often criticised for cross-reactivity, poor sensitivity and specificity. Although serology remains the preferred method in veterinary diagnostic laboratories, serological assays based on surface antigens of C. pecorum have not been established until now. In this study, we evaluated the use of two chlamydial recombinant protein antigens (PmpG and MOMP-G) by a direct IgG ELISA method for detection of ovine anti-chlamydial antibodies. Using the Pepscan method we then identified B cell epitopes across PmpG and MOMP-G proteins, in lambs with (a) naturally occurring asymptomatic C. pecorum infections (b) C. pecorum-associated polyarthritis and (c) recombinant PmpG and MOMP-G vaccine. Plasma IgG antibodies to PmpG in natural infection of lambs were detected earlier in infection than CFT and served as an acute phase marker. Antibodies to MOMP-G IgG were significantly heightened in lambs with C. pecorum-associated polyarthritis. PmpG and MOMP-G specific B-cell epitope mapping revealed epitope responses in immunised lambs cluster with some of the epitope responses in naturally infected lambs. B-cell epitope mapping further revealed that lambs with polyarthritis recognised several unique PmpG (50% frequency, peptide 8, 25, 40, 41 and 50) and MOMP (50% frequency, peptide 50) epitopes in comparison to asymptomatic infections. The findings of this study will have implications towards improved serodiagnosis of C. pecorum infections in livestock and inform the downstream development of alternative peptide-based antigens for future C. pecorum vaccine studies.

Background: A significant proportion of patients treated with warfarin for atrial fibrillation (AF) become warfarin ineligible (WI) due to major bleeding events (MBE) or systemic thromboembolism (STE). We report a large multicenter real-world experience of the use of direct oral antagonists (DOACs) in these WI patients., Methods: We report the outcomes of 263 WI patients treated with DOACs. The primary objective was to evaluate clinical outcomes of STE and MBE with DOACs. Secondary objective was to assess clinical predictors of repeat MBE and STE on DOACs., Results: Note that 63% (166 of 263) patients had a repeat MBE on DOACs. Repeat MBE was significantly higher in patients with prior gastrointestinal bleeding (74.5% vs. 30%, P < 0.0001). Five percent (12 of 263) developed repeat STE. Higher mean CHA2DS2VASC (6.5 ± 1.7 vs. 3.3 ± 1.6 = 0.001) score was associated with repeat STE. About 34% (57 of 166) of patients had an intervention to manage repeat MBE. LAAO devices were successfully used in 67% (12 of 18) high-risk patients who underwent major interventions to manage MBE., Conclusion: In WI patients rechallenged with DOACs, a significant proportion developed repeat MBE. LAAO devices seem reasonable in those patients who undergo major interventions to manage MBE with cautious and temporary continuation of DOAC., (© 2017 Wiley Periodicals, Inc.)

Introduction: Restoration of normal sinus rhythm by radiofrequency ablation (RFA) in atrial fibrillation (AF) patients can result in a reduction of left atrial (LA) volume and pulmonary vein (PV) dimensions. It is not clear if this PV size reduction represents a secondary effect of overall LA volume reduction or true PV stenosis. We assessed the relationship between LA volume reduction and PV orifice area pre- and post-RFA., Methods: A retrospective cohort study was conducted at a tertiary care academic hospital. Pre- and post-RFA cardiac computed tomography (CT) studies of 100 consecutive AF patients were reviewed. Studies identifying obvious segmental PV narrowing were excluded. Left atrial volumes and PV orifice cross-sectional areas (PVOCA) were measured using proprietary software from the CT scanner vendor (GE Healthcare, Waukesha, WI)., Results: The cohort had a mean age of 60 ± 8 years, 73% were male, and 90% were Caucasian. Non-paroxysmal AF was present in 76% of patients with a mean duration from diagnosis to RFA of 55 ± 54 months. Mean procedural time was 244 ± 70 min. AF recurred in 27% at 3 month follow-up. Pre-RFA LA volumes were 132 ± 60 ml and mean PVOCA was 2.89 ± 2.32 cm 2 . In patients with successful ablation, mean LA volume decreased by 10% and PVOCA decreased by 21%. PVOCA was significantly reduced in patients with successful RFA compared to those who had recurrence (2.18 ± 1.12 vs. 2.8 ± 1.9 cm 2 , p = 0.04) but reduction in LA volume between groups was not significant (118 ± 42 vs. 133 ± 54 ml, p=0.15)., Conclusions: The study demonstrates that both PV orifice dimensions and LA volume are reduced after successful AF ablation. These data warrant a reassessment of criteria for diagnosing PV stenosis based on changes in PV caliber alone, ideally incorporating LA volume changes.

Arthritis and kerato-conjunctivitis caused by Chlamydia pecorum in lambs are difficult to diagnose and treat. We tested the ability of a prototype C. pecorum vaccine (SC-vaccine), comprised of C. pecorum major outer membrane protein (MOMP-G) and polymorphic membrane protein G (PmpG), to trigger a Chlamydia-specific humoral and cell-mediated immune response in lambs and pregnant ewes. Vaccinations with the SC-vaccine (one and two injections) were very well tolerated by all ewes and lambs. Although the overall immune responses of ewes to SC-vaccination was poor, their lambs showed stronger antigen-specific immune response than lambs from control vaccine ewes. SC-vaccination in lambs triggered production of systemic anti-MOMP-G and anti-PmpG IgG antibodies and secretory IgA in the ocular mucosa. Double vaccination caused statistically significant increases in the height and duration of the humoral response. Antigen-specific IFN-γ was produced in the peripheral blood mononuclear cells of vaccinated lambs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: In patients who undergo implantable cardiac defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD), data is unclear whether their ICD generator needs to be replaced at end of life if their left ventricular ejection fraction (EF) improves. Despite improvement in EF, the underlying scar may represent a potential substrate for ventricular arrhythmias., Methods: Data on 280 patients who underwent ICD implantation for primary prevention of SCD was obtained from two centers. Patients were followed for any improvement in EF to ≥35%. All arrhythmic events during follow-up, including appropriate and inappropriate shocks/ATP, were recorded., Results: Thirty percent (n = 86/280) of patients improved their EF to >35% of which 41% (n = 37) underwent a generator change by the study ending period with the rest not yet at ERI. Mean baseline EF in patients with and without target EF improvement was 26 ± 7 and 23 ± 7% (p = 0.2). After excluding patients whose arrhythmic events data were unavailable, the final sample consisted of 62 patients in the EF improvement group and 156 patients in the group without EF improvement. In the group with EF improvement, appropriate events (shock + ATP) were noted in 19% of patients (n = 12/62) and inappropriate shocks and ATP in 6% of (n = 4/62) patients after their EF improved to >35%. Four patients received appropriate therapies when their EF was low prior to improvement. In contrast, in patients who had no improvement in EF, 27% (n = 43/156) received an appropriate therapy (p = 0.6) while 11% (n = 18/156) (p = 0.2) received inappropriate shocks and ATP. All-cause mortality was higher in patients without subsequent improvement in EF versus those with EF improvement (31 vs. 15% (p = .005)., Conclusions: There was no significant difference in the number of appropriate therapies received by each group. Patients continue to be at high risk for sudden cardiac death despite improvement in EF.

Background: Use of corticosteroids before and after atrial fibrillation (AF) ablation can decrease acute inflammation and reduce AF recurrence., Purpose: To assess the efficacy of oral prednisone in improving the outcomes of pulmonary vein isolation with radiofrequency ablation and its effect on inflammatory cytokine., Methods: A total of 60 patients with paroxysmal AF undergoing radiofrequency ablation were randomized (1:1) to receive either 3 doses of 60 mg daily of oral prednisone or a placebo. Inflammatory cytokine levels (TNF-α, IL-1, IL6, IL-8) were measured at baseline, prior to ablation, immediately after ablation, and 24 hours post ablation. Patients underwent 30 day event monitoring at 3 months, 6 months and 12 months post procedure., Results: Immediate post ablation levels of inflammatory cytokines were lower in the steroid group when compared to the placebo group; IL-6: 9.0 ±7 vs 15.8 ±13 p=0.031; IL-8: 10.5 ±9 vs 15.3 ±8; p=0.047 respectively. Acute PV reconnection rates during the procedure (7/23% vs 10/36%; p = 0.39), and RF ablation time (51±13 vs 56±11 min, p = 0.11) trended to be lower in the placebo group than the steroid group. There was no difference in the incidence of early recurrence of AF during the blanking period and freedom from AF off AAD at 12 months between both groups (5/17% vs 8/27%; p = 0.347 and 21/70% vs 18/60%; p=0.417 in placebo and steroid groups respectively)., Conclusion: Although oral corticosteroids have significant effect in lowering certain cytokines, it did not impact the clinical outcomes of AF ablation.

Background: There have been an increasing number of atrial fibrillation (AF) patients with Watchman left atrial appendage occlusion (LAAO) device, requiring catheter ablation (CA) for maintenance of normal sinus rhythm. In this study, we describe our experience with the feasibility and safety of CA in patients with a preexisting Watchman LAAO device., Methods: This was a retrospective multicenter AF registry of 60 patients with Watchman LAAO device who underwent CA for AF. Baseline clinical and procedural characteristics of the included subjects were retrieved from review of medical records and were analyzed., Results: The mean age was 72.7 ± 4.9 years and the mean CHADS2 score was 2.3 ± 0.6. All patients had successful pulmonary vein isolation (PVI). The left atrial appendage (LAA) was electrically active in 34 (56%) while reentrant tachycardia and AF triggers were seen in 17 (28%) patients. Electrical isolation was attempted in these 17 patients with only 10 achieving complete LAA isolation. Repeat imaging showed new peri-device leaks in 30% (12/40) patients, while new significant peri-device leaks (≥5 mm) were noted in 10% (10/40) of patients after RFA, respectively, requiring continuation of oral anticoagulation. There were a higher proportion of patients with severe peri-device leaks (≥5 mm) after LAA isolation. However, >50% of those leaks sealed off on follow-up transesophageal echocardiogram., Conclusion: AF ablation is a feasible and safe in patients with preexisting Watchman LAAO device. Electrical isolation of the LAA could be difficult and when attempted can result in increased risk of short-term peri-device leak and recurrence of AT/AF in almost all patients., (© 2016 Wiley Periodicals, Inc.)

The objective of this study was to examine the clinical determinants of incidence and prognosis of arrhythmias in the setting of acute brain injury. Acute brain injury is known to cause electrocardiographic abnormalities and cardiac arrhythmias. The relation between partial brain tissue oxygen (PBTO) and intracranial pressure (ICP) with arrhythmia incidence and prognosis remains unknown. Consecutive patients with acute brain injury and intracranial bleed admitted to the neurosurgical intensive care unit were enrolled in the study. Baseline characteristics [demographics, medical history, etiology of brain injury, Glasgow Coma Scale (GCS) score, blood pressure, and respiratory rate] were documented. Patient's telemetry recordings were reviewed for daily mean heart rates and arrhythmias. If arrhythmia was noted, PBTO levels at the beginning of arrhythmia, ICP, brain tissue temperature, and outcomes were recorded. A total of 106 subjects (53% men, age 39 ± 18 years, 65 traumatic and 41 nontraumatic brain injuries) were studied. Overall, 62% of subjects developed a total of 241 arrhythmia episodes. Ventricular arrhythmias were associated with significantly higher daily mean heart rates, low PBTO levels, and low GCS scores, whereas atrial arrhythmias were associated with lower daily mean heart rates, normal PBTO levels, and higher GCS and ICP. Three or more episodes of arrhythmia predicted worse outcomes, including mortality (P = 0.001). In patients with acute brain injury, poor PBTO levels are associated with higher incidence of ventricular tachyarrhythmias. In contrast, atrial tachyarrhythmias occur in patients with normal PBTO levels and higher ICP. Incidence of ventricular arrhythmia in those with poor PBTO is associated with increased mortality.

Background: Arthritis is an economically significant disease in lambs and is usually the result of a bacterial infection. One of the known agents of this disease is Chlamydia pecorum, a globally recognised livestock pathogen associated with several diseases in sheep, cattle and other hosts. Relatively little published information is available on the clinical, diagnostic and pathologic features of C. pecorum arthritis in sheep, hindering efforts to enhance our understanding of this economically significant disease. In this case series, a combination of standard diagnostic testing used routinely by veterinarians, such as the Chlamydia complement fixation text (CFT), veterinary clinical examinations, and additional screening via C. pecorum specific qPCR was used to describe putative chlamydial infections in five sheep flocks with suspected ovine arthritis., Case Presentation: Five separate cases involving multiple lambs (aged six to ten months) of different breeds with suspected C. pecorum arthritis are presented. In two of the five cases, arthritic lambs exhibited marked depression and lethargy. Arthritis with concurrent conjunctivitis was present in four out of five lamb flocks examined. Chlamydia CFT demonstrated medium to high positive antibody titres in all flocks examined. C. pecorum shedding was evident at multiple sites including the conjunctiva, rectum and vagina, as determined via qPCR. Two of the five flocks received antimicrobials and all flocks recovered uneventfully regardless of treatment., Conclusion: This case series highlights the features a field veterinarian may encounter in cases of suspected ovine chlamydial arthritis. Our analysis suggests a presumptive diagnosis of chlamydial arthritis in lambs can be made when there is evidence of joint stiffness with or without synovial effusion and elevated chlamydia antibody titres. C. pecorum-specific qPCR was found to be a useful ancillary diagnostic tool, detecting Chlamydia positivity in low or negative CFT titre animals. Variables such as symptom duration relative to sampling, sheep breed and farm management practices were all factors recorded that paint a complex epidemiological and diagnostic picture for this disease. These case studies serve to provide a platform for further research to improve diagnostic testing and new treatment and control strategies for C. pecorum infections in sheep.

Background: Published studies of epicardial ligation of left atrial appendage (LAA) have reported discordant results., Objective: The purpose of this study was to delineate the safety and efficacy of LAA closure with the LARIAT device., Methods: This is a multicenter registry of 712 consecutive patients undergoing LAA ligation with LARIAT at 18 US hospitals. The primary end point was successful suture deployment, no leak by intraprocedural transesophageal echocardiography (TEE), and no major complication (death, stroke, cardiac perforation, and bleeding requiring transfusion) at discharge. A leak of 2-5 mm on follow-up TEE was the secondary end point., Results: LARIAT was successfully deployed in 682 patients (95.5%). A complete closure was achieved in 669 patients (98%), while 13 patients (1.8%) had a trace leak (<2 mm). There was 1 death related to the procedure. Ten patients (1.44%) had cardiac perforation necessitating open heart surgery, while another 14 (2.01%) did not need surgery. The risk of cardiac perforation decreased significantly after the introduction of a micropuncture (MP) needle for pericardial access. Delayed complications (pericarditis requiring >2 weeks of treatment with nonsteroidal anti-inflammatory drugs/colchicine and pericardial and pleural effusion after discharge) occurred in 34 (4.78%) patients, and the risk decreased significantly with the periprocedural use of colchicine. Follow-up TEE (n = 480) showed a leak of 2-5 mm in 6.5% and a thrombus in 2.5%. One patient had a leak of >5 mm., Conclusion: LARIAT effectively closes the LAA and has acceptable procedural risks with the evolution of the use of the micropuncture needle for pericardial access and the use of colchicine for mitigating the postinflammatory response associated with LAA ligation and pericardial access., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Atrioventricular node (AVN) ablation is an effective treatment for symptomatic patients with atrial arrhythmias who are refractory to rhythm and rate control strategies where optimal ventricular rate control is desired. There are limited data on the predictors of failure of AVN ablation. Our objective was to identify the predictors of failure of AVN ablation. This is an observational single-center study of consecutive patients who underwent AVN ablation in a large academic center. Baseline characteristics, procedural variables, and outcomes of AVN ablation were collected. AVN "ablation failure" was defined as resumption of AVN conduction resulting in recurrence of either rapid ventricular response or suboptimal biventricular pacing. A total of 247 patients drug refractory AF who underwent AVN ablation at our center with a mean age of 71 ± 12 years with 46% being males were included. Ablation failure was seen in 11 (4.5%) patients. There were no statistical differences between patients with "ablation failure" versus "ablation success" in any of the baseline clinical variables. Patients with moderate-to-severe tricuspid regurgitation (TR) were much more likely to have ablation failure than those with ablation success (8 [73%] vs 65 [27%]; p = 0.003). All 11 patients with ablation failure had a successful redo procedure, 9 with right and 2 with the left sided approach. On multivariate analysis, presence of moderate-to-severe TR was found to be the only predictor of failure of AVN ablation (odds ratio 9.1, confidence interval 1.99 to 42.22, p = 0.004). In conclusion, moderate-to-severe TR is a strong and independent predictor of failure of AVN ablation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The left atrial appendage (LAA) is a well-known source of atrial natriuretic peptide (ANP) and therefore plays an important role in homeostasis. The neurohormonal impact of epicardial exclusion of the LAA with the LARIAT procedure is unknown. In this proof-of-concept study, we postulated that LAA exclusion would impact homeostasis as evidenced by changes in electrolytes and blood pressure (BP)., Methods: A total of 76 patients who underwent successful LAA exclusion were enrolled in this retrospective observational study utilizing a prospective registry. Electrolytes, BP, and heart rate (HR) were monitored before LARIAT and post-LARIAT (24 and 72 h and 6 months)., Results: There was a significant reduction of systolic BP (mmHg) at 24 h (113.3 ± 16.0; p < 0.0001) and 72 h (119.0 ± 18.4 mmHg; p < 0.0001) post-LARIAT when compared with pre-LARIAT BP (138.2 ± 21.3). The reduction in systolic BP persisted at 6-month follow-up (128.8 ± 17.3; p = 0.0005). There was significant reduction in serum sodium (mmol/L) at 24 h (135.4 ± 3.6; p < 0.0001) and 72 h (136.3 ± 3.7; p < 0.001) post-LARIAT when compared to pre-LARIAT (138.7 ± 3.2). The reduction in sodium was not persistent at 6-month follow-up (138.4 ± 3.3; p = 0.453)., Conclusions: LAA exclusion results in an early and persistent decrease in systolic BP. Additionally, there is an early decline in serum sodium, which normalizes at long-term follow-up. The underlying mechanism leading to these changes is not entirely clear; however, it is likely related to neurohormonal changes post LAA exclusion.

Background: Neurocardiogenic syncope (NCS) is a common clinical condition characterized by abrupt cardiovascular autonomic changes resulting in syncope. This is a recurring condition with mixed results from current strategies of treatment., Methods: Subjects with a diagnosis of NCS were screened and enrolled. All the participants were given a DVD containing yoga videos and were instructed to practice yoga therapy for 60 min, three times a week for 3 consecutive months. Syncope functional status questionnaire score (SFSQS) was administered at the beginning and the end of the study. The subjects were followed for 3 months and underwent repeat tilt table testing at the end of the study., Results: Of the 60 patients screened, 44 subjects were enrolled, 21 in the intervention group and 23 in the control group. Most of the participants were females, and the mean age was 21 ± 3 years. In the intervention group, who finished the yoga regimen, there was a statistically significant improvement from control phase to the intervention phase, in number of episodes of syncope (4 ± 1 vs 1.3 ± 0.7, p < 0.001) and presyncope (4.7 ± 1.5 vs 1.5 ± 0.5, p < 0.001). The mean SFSQS also decreased from 67 ± 7.8 to 29.8 ± 4.6 (p < 0.001). All subjects had positive head up tilt table (HUTT) study at the time of enrollment compared to only six patients at the completion of intervention phase (10/100 vs 6/28 %, p < 0.0001)., Conclusion: Yoga therapy can potentially improve the symptoms of presyncope and syncope in young female patients with NCS.