The use of dipeptide supplementation as a means of mitigating the negative effects of dietary soybean meal on Zebrafish Danio rerio.

Soybean meal (SBM) inclusion in aquaculture diets has been found to negatively affect growth and induce intestinal inflammation in fish. The objective of this study was to determine the effect of health-promoting dipeptide supplementation into SBM-based feeds on growth performance, intestinal health, and muscle free amino acid composition, an indicator of dietary amino acid availability, in a zebrafish model. There were five treatment groups in this study. The first group ((+) Control) received a fishmeal-based diet. The second group ((-) Control) received SBM-based diet. The last three groups (Ala-Glu, Car, and Ans) were fed SBM-based diets, supplemented with alanyl-glutamine, carnosine, and anserine respectively. The Ala-Glu and Car groups experienced a significantly higher weight gain than the (-) Control group, weighing 35.38% and 33.96% more, respectively at the conclusion of the study. There were no significant differences in gene expression among the groups, but Ala-Glu had the highest expression of both nutrient absorption genes measured, PepT1 and fabp2. Ala-Glu had significantly longer intestinal villi, and a significantly higher villus length-to-width ratio than the (-) Control group. The Car group had a significantly higher post-prandial tissue concentration of lysine, compared to the (-) Control group. The increase in villus surface area and expression of nutrient absorption genes represent an improvement in intestinal absorptive capacity in the Ala-Glu group. The results from this study provide support for the use of alanyl-glutamine and carnosine supplementation as a means of improving growth performance of zebrafish fed with a high level SBM-based diet.

Berberine alters gut microbial function through modulation of bile acids.

BACKGROUND: Berberine (BBR) is a plant-based nutraceutical that has been used for millennia to treat diarrheal infections and in contemporary medicine to improve patient lipid profiles. Reduction in lipids, particularly cholesterol, is achieved partly through up-regulation of bile acid synthesis and excretion into the gastrointestinal tract (GI). The efficacy of BBR is also thought to be dependent on structural and functional alterations of the gut microbiome. However, knowledge of the effects of BBR on gut microbiome communities is currently lacking. Distinguishing indirect effects of BBR on bacteria through altered bile acid profiles is particularly important in understanding how dietary nutraceuticals alter the microbiome. RESULTS: Germfree mice were colonized with a defined minimal gut bacterial consortium capable of functional bile acid metabolism (Bacteroides vulgatus, Bacteroides uniformis, Parabacteroides distasonis, Bilophila wadsworthia, Clostridium hylemonae, Clostridium hiranonis, Blautia producta; B4PC2). Multi-omics (bile acid metabolomics, 16S rDNA sequencing, cecal metatranscriptomics) were performed in order to provide a simple in vivo model from which to identify network-based correlations between bile acids and bacterial transcripts in the presence and absence of dietary BBR. Significant alterations in network topology and connectivity in function were observed, despite similarity in gut microbial alpha diversity (P = 0.30) and beta-diversity (P = 0.123) between control and BBR treatment. BBR increased cecal bile acid concentrations, (P < 0.05), most notably deoxycholic acid (DCA) (P < 0.001). Overall, analysis of transcriptomes and correlation networks indicates both bacterial species-specific responses to BBR, as well as functional commonalities among species, such as up-regulation of Na+/H+ antiporter, cell wall synthesis/repair, carbohydrate metabolism and amino acid metabolism. Bile acid concentrations in the GI tract increased significantly during BBR treatment and developed extensive correlation networks with expressed genes in the B4PC2 community. CONCLUSIONS: This work has important implications for interpreting the effects of BBR on structure and function of the complex gut microbiome, which may lead to targeted pharmaceutical interventions aimed to achieve the positive physiological effects previously observed with BBR supplementation.

Can intestinal absorption of dietary protein be improved through early exposure to plant-based diet?

Nutritional Programming (NP) has been studied as a means of mitigating the negative effects of dietary plant protein (PP), but the optimal timing and mechanism behind NP are still unknown. The objectives of this study were: 1) To determine whether zebrafish (Danio rerio) can be programmed to soybean meal (SBM) through early feeding and broodstock exposure to improve SBM utilization; 2) To determine if NP in zebrafish affects expression of genes associated with intestinal nutrient uptake; 3) To determine if early stage NP and/or broodstock affects gene expression associated with intestinal inflammation or any morphological changes in the intestinal tract that might improve dietary SBM utilization. Two broodstocks were used to form the six experimental groups. One broodstock group received fishmeal (FM) diet (FMBS), while the other was fed ("programmed with") SBM diet (PPBS). The first ((+) Control) and the second group ((-) Control) received FM and SBM diet for the entire study, respectively, and were progeny of FMBS. The last four groups consisted of a non-programmed (FMBS-X-PP and PPBS-X-PP) and a programmed group (FMBS-NP-PP and PPBS-NP-PP) from each of the broodstocks. The programming occurred through feeding with SBM diet during 13-23 dph. The non-control groups underwent a PP-Challenge, receiving SBM diet during 36-60 dph. During the PP-Challenge, both PPBS groups experienced significantly lower weight gains than the (+) Control group. NP in early life stages significantly increased the expression of PepT1 in PPBS-NP-PP, compared to PPBS-X-PP. NP also tended to increase the expression of fabp2 in the programmed vs. non-programmed groups of both broodstocks. The highest distal villus length-to-width ratio was observed in the dual-programmed group, suggesting an increase in surface area for nutrient absorption within the intestine. The results of this study suggest that NP during early life stages may increase intestinal absorption of nutrients from PP-based feeds.

Nutritional programming improves dietary plant protein utilization in zebrafish Danio rerio.

Nutritional Programming (NP) has been shown to counteract the negative effects of dietary plant protein (PP) by introducing PP at an early age towards enhancement of PP utilization during later life stages. This study explored the effect of NP and its induction time on growth, expression of appetite-stimulating hormones, and any morphological changes in the gut possibly responsible for improved dietary PP utilization. At 3 days post-hatch (dph) zebrafish were distributed into 12 (3 L) tanks, 100 larvae per tank. This study included four groups: 1) The control (NP-FM) group received fishmeal (FM)-based diet from 13-36 dph and was challenged with PP-based diet during 36-66 dph; 2) The NP-PP group received NP with dietary PP in larval stage via live food enrichment during 3-13 dph followed by FM diet during 13-36 dph and PP diet during 36-66 dph; 3) The T-NP group received NP between 13-23 dph through PP diet followed by FM diet during 23-36 dph and PP diet during 36-66 dph; and 4) The PP group received PP diet from 13-66 dph. During the PP challenge the T-NP group achieved the highest weight gain compared to control and PP. Ghrelin expression in the brain was higher in T-NP compared to NP-FM and NP-PP, while in the gut it was reduced in both NP-PP and T-NP groups. Cholecystokinin expression showed an opposite trend to ghrelin. The brain neuropeptide Y expression was lower in NP-PP compared to PP but not different with NP-FM and T-NP groups. The highest villus length to width ratio in the middle intestine was found in T-NP compared to all other groups. The study suggests that NP induced during juvenile stages improves zebrafish growth and affects digestive hormone regulation and morphology of the intestinal lining-possible mechanisms behind the improved PP utilization in pre-adult zebrafish stages.

Thyroid cytopathology: updates and molecular testing.

The utility of fine needle aspiration (FNA) is well described in the context of evaluating thyroid lesions. Among the various international systems of classification of thyroid cytology, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has also provided a sound framework to standardize the reporting of FNA cytology results. New molecular evidence and clinical studies demonstrated the need for revision of the nomenclature resulting in introduction of new categories, such as the noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Indeterminate thyroid cytology results pose a challenge for further management and the continued development of molecular markers may aid in the management of indeterminate thyroid lesions.

SMARTA: Automated testing apparatus for visual discrimination tasks.

This article introduces the open-source Subject-Mediated Automatic Remote Testing Apparatus (SMARTA) for visual discrimination tasks, which aims to streamline and ease data collection, eliminate or reduce observer error, increase interobserver agreement, and automate data entry without the need for an internet connection. SMARTA is inexpensive and easy to build, and it can be modified to accommodate a variety of experimental designs. Here we describe the utility and functionality of SMARTA in a captive setting. We present the results from a case study of color vision in ruffed lemurs (Varecia spp.) at the Duke Lemur Center in Durham, North Carolina, in which we demonstrate SMARTA's utility for two-choice color discrimination tasks, as well as its ability to streamline and standardize data collection. We also include detailed instructions for constructing and implementing the fully integrated SMARTA touchscreen system.

Acute Hemodynamic Effects of Biventricular Pacing After Left Ventricular Assist Device.

BACKGROUND: Despite cardiac resynchronization therapy (CRT), some patients with heart failure progress and undergo left ventricular assist device (LVAD) implantation. Management of CRT after LVAD implantation has not been well studied. The purpose of this study was to determine whether RV pacing or biventricular pacing measurably affects acute hemodynamics in patients with an LVAD and a CRT device. METHODS AND RESULTS: Seven patients with CRT and LVAD underwent right heart catheterization. Pressures and oximetry were measured and LVAD parameters were recorded during 3 different conditions: RV pacing alone, biventricular pacing, and intrinsic atrioventricular conduction. Paired t tests were used to evaluate changes within subjects. There were no significant changes in right atrial pressure, pulmonary arterial pressures, pulmonary capillary wedge pressure, cardiac index, or any LVAD parameter (P > .05). CONCLUSIONS: Our data suggest that CRT probably has no acute hemodynamic effect in patients with LVADs, but further study is needed.

The Effectiveness of Intravenous Golimumab Administered Directly After Infliximab in Rheumatoid Arthritis Patients.

PURPOSE: For patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF. METHODS: Patient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy. FINDINGS: Significant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p < 0.05). Limited changes were observed through the RAPID3 and PtGA. CONCLUSIONS: Findings from this study indicate that intravenous golimumab is effective in managing RA in a population of patients switching directly from infliximab (mean last dose 7.4 mg/kg).

Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify additional rare variants and novel genes potentially contributing to AD. METHODS: Whole exome sequencing was performed on 23 multi-generational families with an average of eight affected subjects. Exome sequencing was filtered for rare, nonsynonymous and loss-of-function variants. Alterations predicted to have a functional consequence and located within either a previously reported AD gene, a linkage peak (LOD>2), or clustering in the same gene across multiple families, were prioritized. RESULTS: Rare variants were found in known AD risk genes including AKAP9, CD33, CR1, EPHA1, INPP5D, NME8, PSEN1, SORL1, TREM2 and UNC5C. Three families had five variants of interest in linkage regions with LOD>2. Genes with segregating alterations in these peaks include CD163L1 and CLECL1, two genes that have both been implicated in immunity, CTNNA1, which encodes a catenin in the cerebral cortex and MIEF1, a gene that may induce mitochondrial dysfunction and has the potential to damage neurons. Four genes were identified with alterations in more than one family include PLEKHG5, a gene that causes Charcot-Marie-Tooth disease and THBS2, which promotes synaptogenesis. CONCLUSION: Utilizing large families with a heavy burden of disease allowed for the identification of rare variants co-segregating with disease. Variants were identified in both known AD risk genes and in novel genes.

Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease.

Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4076 NHW and 1157 AA cases and controls. We confirm three previously associated ABCA7 risk variants and extend two of these associations to other populations, an intronic variant in NHW (P=3.0×10-3) (originally reported in a Belgian population), and a splice variant originally associated in the Icelandic population, which was significantly associated in the NHW cohort (P=1.2×10-6) and nominally associated in the AA cohort (P=0.017). We also identify a 3'-UTR splice variant that segregates in four siblings of one family and is nominally associated with LOAD (P=0.040). Multiple variants in ABCA7 contribute to LOAD risk.

Thermally driven bubble evolution at a heater wire in water characterized by high-speed transmission electron microscopy.

This work investigates the early stage evolution of thermally nucleated microbubbles in water using in situ high-speed, 400 fps, transmission electron microscopy. A Pt wire Joule heater induced bubble nucleation and growth from air-saturated water at different levels of power. For all powers below Pt breakdown, the dissolved gas initiates bubble nucleation at the concave surface defects adjacent to the area of highest temperature. A combination of interfacial forces and stress relaxation drive rapid migration of the bubbles away from the nucleation site. Thermocapillary forces ultimately dominate and drive their return to the region of highest temperature. The dynamic response highlights the importance of this length and time domain, which has until now received limited direct study.

Significant Discrepancy Between Estimated and Actual Longevity in St. Jude Medical Implantable Cardioverter-Defibrillators.

BACKGROUND: Real-time estimated longevity has been reported in pacemakers for several years, and was recently introduced in implantable cardioverter-defibrillators (ICDs). OBJECTIVE: We sought to evaluate the accuracy of this longevity estimate in St. Jude Medical (SJM) ICDs, especially as the device battery approaches depletion. METHODS: Among patients with SJM ICDs who underwent generator replacements due to reaching elective replacement indicator (ERI) at our institution, we identified those with devices that provided longevity estimates and reviewed their device interrogations in the 18 months prior to ERI. Significant discrepancy was defined as a difference of more than 12 months between estimated and actual longevity at any point during this period. RESULTS: Forty-six patients with Current/Promote devices formed the study group (40 cardiac resynchronization therapy [CRT] and 6 single/dual chamber). Of these, 34 (74%) had significant discrepancy between estimated and actual longevity (28 CRT and all single/dual). Longevity was significantly overestimated by the device algorithm (mean maximum discrepancy of 18.8 months), more in single/dual than CRT devices (30.5 vs. 17.1 months). Marked discrepancy was seen at voltages ≥2.57 volts, with maximum discrepancy at 2.57 volts (23 months). The overall longevity was higher in the discrepant group of CRT devices than in the nondiscrepant group (67 vs. 61 months, log-rank P = 0.03). CONCLUSIONS: There was significant overestimation of longevity in nearly three-fourths of Current/Promote SJM ICDs in the last 18 months prior to ERI. Longevity estimates of SJM ICDs may not be reliable for making clinical decisions on frequency of follow-up, as the battery approaches depletion.

Prevalence and Electrocardiographic and Electrophysiological Characteristics of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract.

BACKGROUNDS: Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from both the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the prevalence and electrocardiographic and electrophysiological characteristics of these idiopathic intramural LVOT VAs when compared with the idiopathic endocardial and epicardial LVOT VAs. METHODS AND RESULTS: We studied 82 consecutive VAs with origins in the aortomitral continuity (n=30), LV summit (n=34), and intramural site (n=18). The maximum deflection index (the time to the maximum deflection in the precordial leads/QRS duration) was the largest in LV summit VAs (0.52±0.07), smallest in aortomitral continuity VAs (0.45±0.06), and midrange in intramural VAs (0.49±0.05). The electrocardiographic and electrophysiological characteristics of the intramural LVOT VAs were similar to those of the aortomitral continuity VAs. The intramural LVOT VAs exhibited a significantly smaller R-wave amplitude ratio in leads III to II, and ratio of the Q-wave amplitude in leads aVL to aVR, and a significantly earlier and later local ventricular activation time relative to the QRS onset at the His bundle and successful ablation sites than the LV summit VAs, respectively. CONCLUSIONS: Intramural sites account for a significant proportion of LVOT VAs. The electrocardiographic and electrophysiological characteristics of the idiopathic intramural LVOT VAs were midrange between those of the idiopathic endocardial and epicardial LVOT VAs, and more similar to those of the idiopathic endocardial LVOT VAs than those of the idiopathic epicardial LVOT VAs.

GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis.

To identify genes and biologically relevant pathways associated with risk to develop multiple sclerosis (MS), the Genome-Wide Association Studies noise reduction method (GWAS-NR) was applied to MS genotyping data. Regions of association were defined based on the significance of linkage disequilibrium blocks. Candidate genes were cross-referenced based on a review of current literature, with attention to molecular function and directly interacting proteins. Supplementary annotations and pathway enrichment scores were generated using The Database for Annotation, Visualization and Integrated Discovery. The candidate set of 220 MS susceptibility genes prioritized by GWAS-NR was highly enriched with genes involved in biological pathways related to positive regulation of cell, lymphocyte and leukocyte activation (P=6.1E-15, 1.2E-14 and 5.0E-14, respectively). Novel gene candidates include key regulators of NF-κB signaling and CD4+ T helper type 1 (Th1) and T helper type 17 (Th17) lineages. A large subset of MS candidate genes prioritized by GWAS-NR were found to interact in a tractable pathway regulating the NF-κB-mediated induction and infiltration of pro-inflammatory Th1/Th17 T-cell lineages, and maintenance of immune tolerance by T-regulatory cells. This mechanism provides a biological context that potentially links clinical observations in MS to the underlying genetic landscape that may confer susceptibility.

Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.

BACKGROUNDS: Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. METHODS AND RESULTS: Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <-30 ms was recorded at those ablation sites. CONCLUSIONS: LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides.

The development of global vaccine stockpiles.

Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles.

Conversion of S-phenylsulfonylcysteine residues to mixed disulfides at pH 4.0: utility in protein thiol blocking and in protein-S-nitrosothiol detection.

A three step protocol for protein S-nitrosothiol conversion to fluorescent mixed disulfides with purified proteins, referred to as the thiosulfonate switch, is explored which involves: (1) thiol blocking at pH 4.0 using S-phenylsulfonylcysteine (SPSC); (2) trapping of protein S-nitrosothiols as their S-phenylsulfonylcysteines employing sodium benzenesulfinate; and (3) tagging the protein thiosulfonate with a fluorescent rhodamine based probe bearing a reactive thiol (Rhod-SH), which forms a mixed disulfide between the probe and the formerly S-nitrosated cysteine residue. S-Nitrosated bovine serum albumin and the S-nitrosated C-terminally truncated form of AdhR-SH (alcohol dehydrogenase regulator) designated as AdhR*-SNO were selectively labelled by the thiosulfonate switch both individually and in protein mixtures containing free thiols. This protocol features the facile reaction of thiols with S-phenylsulfonylcysteines forming mixed disulfides at mild acidic pH (pH = 4.0) in both the initial blocking step as well as in the conversion of protein-S-sulfonylcysteines to form stable fluorescent disulfides. Labelling was monitored by TOF-MS and gel electrophoresis. Proteolysis and peptide analysis of the resulting digest identified the cysteine residues containing mixed disulfides bearing the fluorescent probe, Rhod-SH.

A novel electrocardiographic criterion for differentiating a left from right ventricular outflow tract tachycardia origin: the V2S/V3R index.

INTRODUCTION: Although several ECG criteria have been proposed for differentiating between left and right origins of idiopathic ventricular arrhythmias (VA) originating from the outflow tract (OT-VA), their accuracy and usefulness remain limited. This study was undertaken to develop a more accurate and useful ECG criterion for differentiating between left and right OT-VA origins. METHODS AND RESULTS: We studied OT-VAs with a left bundle branch block pattern and inferior axis QRS morphology in 207 patients who underwent successful catheter ablation in the right (RVOT; n = 154) or left ventricular outflow tract (LVOT; n = 53). The surface ECGs during the OT-VAs and during sinus beats were analyzed with an electronic caliper. The V2S/V3R index was defined as the S-wave amplitude in lead V2 divided by the R-wave amplitude in lead V3 during the OT-VA. The V2S/V3R index was significantly smaller for LVOT origins than RVOT origins (P < 0.001). The area under the curve (AUC) for the V2S/V3R index by a receiver operating characteristic analysis was 0.964, with a cut-off value of ≤1.5 predicting an LVOT origin with an 89% sensitivity and 94% specificity. In the AUC and accuracy, the V2S/V3R index was superior to any previously proposed ECG criteria in an analysis of all OT-VAs. This advantage of the V2S/V3R index over the V2 transition ratio and other indices also held true for a subanalysis of 77 OT-VAs with a lead V3 precordial transition. CONCLUSION: The V2S/V3R index outperformed other ECG criteria to differentiate left from right OT-VA origins independent of the site of the precordial transition.

Prevalence and clinical, electrocardiographic, and electrophysiologic characteristics of ventricular arrhythmias originating from the noncoronary sinus of Valsalva.

BACKGROUND: Idiopathic ventricular arrhythmias (VAs) can be rarely ablated from the noncoronary cusp (NCC) of the aorta. OBJECTIVE: The purpose of this study was to investigate the prevalence and the clinical, electrocardiographic, and electrophysiologic characteristics of idiopathic NCC VAs. METHODS: We studied 90 consecutive patients who underwent successful catheter ablation of idiopathic aortic root VAs (left coronary cusp [LCC] 33, right coronary cusp [RCC] 32, junction between LCC and RCC 19, NCC = 6). RESULTS: NCC VAs occurred in significantly younger patients (all <40 years old) and exhibited a shorter QRS duration (all but one <150 ms), smaller R-wave amplitude ratio in leads II and III (III/II), earlier ventricular activation in the His bundle (HB) region (all but one preceded QRS onset by >25 ms), and larger atrial to ventricular electrogram amplitude ratio (A/V) at the successful ablation site (all but one >1) than the other VAs. QRS morphology of the NCC VAs was similar to that of RCC VAs, but NCC VAs always exhibited a left bundle branch block and left superior (n = 1) or inferior axis (n = 5). All NCC VAs exhibited ventricular tachycardias, although premature ventricular contractions were dominant in the other VAs. CONCLUSION: NCC VAs were very rare (7%) and occurred in significantly younger patients than those among the other aortic root VAs. In a limited set of six patients, the ECG and electrophysiologic characteristics of NCC VAs were similar to those of RCC VAs but were characterized by narrower QRS duration, smaller III/II ratio, earlier ventricular activation in the HB region, and A/V ratio >1 at the successful ablation site.

Cardiovascular implantable electronic device implantation with uninterrupted dabigatran: comparison to uninterrupted warfarin.

BACKGROUND: While continuation of oral anticoagulation (OAC) with warfarin may be preferable to interruption and bridging with heparin for patients undergoing cardiovascular implantable electronic device (CIED) implantation, it is uncertain whether the same strategy can be safely used with dabigatran. OBJECTIVE AND METHODS: To determine the risk of bleeding and thromboembolic complications associated with uninterrupted OAC during CIED implantation, replacement, or revision, the outcomes of patients receiving uninterrupted dabigatran (D) were compared to those receiving warfarin (W). RESULTS: D was administered the day of CIED implant in 48 patients (age 66 ± 12.4 years, 13 F and 35 M, 21 ICDs and 27 PMs), including new implant in 25 patients, replacement in 14 patients, and replacement plus lead revision in 9 patients. D was held the morning of the procedure in 14 patients (age 70 ± 11 years, 4 F and 10 M, 5 ICDs and 9 PMs). W was continued in 195 patients (age 60 ± 14.4 years, 54 F, and 141 M), including new implant in 122 patients, replacement in 33 patients, and replacement plus lead revision or upgrade in 40 patients. Bleeding complications occurred in 1 of 48 patients (2.1%) with uninterrupted dabigatran (a late pericardial effusion), 0 of 14 with interrupted D, and 9 of 195 patients (4.6%) on W (9 pocket hematomas), P = 0.69. Fifty percent of bleeding complications were associated with concomitant antiplatelet medications. CONCLUSIONS: The incidence of bleeding complications is similar during CIED implantation with uninterrupted D or W. The risks are higher when OAC is combined with antiplatelet drugs.