Electrocardiographic imaging demonstrates electrical synchrony improvement by dynamic atrioventricular delays in patients with left bundle branch block and preserved atrioventricular conduction

Aims: Cardiac resynchronization therapy programmed to dynamically fuse pacing with intrinsic conduction using atrioventricular (AV) timing algorithms (e.g. SyncAV) has shown promise; however, mechanistic data are lacking. This study assessed the impact of SyncAV on electrical dyssynchrony across various pacing modalities using non-invasive epicardial electrocardiographic imaging (ECGi). Methods and results: Twenty-five patients with left bundle-branch block (median QRS duration (QRSd) 162.7 ms) and intact AV conduction (PR interval 174.0 ms) were prospectively enrolled. ECGi was performed acutely during biventricular pacing with fixed nominal AV delays (BiV) and using SyncAV (optimized for the narrowest QRSd) during: BiV + SyncAV, LV-only single-site (LVSS + SyncAV), MultiPoint pacing (MPP + SyncAV), and LV-only MPP (LVMPP + SyncAV). Dyssynchrony was quantified via ECGi (LV activation time, LVAT; RV activation time, RVAT; LV electrical dispersion index, LVEDi; ventricular electrical uncoupling index, VEU; and biventricular total activation time, VVtat). Intrinsic conduction LVAT (124 ms) was significantly reduced by BiV pacing (109 ms) (P = 0.001) and further reduced by LVSS + SyncAV (103 ms), BiV + SyncAV (103 ms), LVMPP + SyncAV (95 ms), and MPP + SyncAV (90 ms). Intrinsic RVAT (93 ms), VVtat (130 ms), LVEDi (36 ms), VEU (50 ms), and QRSd (163 ms) were reduced by SyncAV across all pacing modes. More patients exhibited minimal LVAT, VVtat, LVEDi, and QRSd with MPP + SyncAV than any other modality. Conclusion: Dynamic AV delay programming targeting fusion with intrinsic conduction significantly reduced dyssynchrony, as quantified by ECGi and QRSd for all evaluated pacing modes. MPP + SyncAV achieved the greatest synchrony overall but not for all patients, highlighting the value of pacing mode individualization during fusion optimization

Optimization of left ventricular pacing site plus multipoint pacing improves remodeling and clinical response to cardiac resynchronization therapy at 1 year

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Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The Roles of Realistic Cardiac Structure in Conduction and Conduction Block: Studies of Novel Micropatterned Cardiac Cell Cultures

<p>The role of cardiac tissue structure in both normal and abnormal impulse conduction has been extensively studied by researchers in cardiac electrophysiology. However, much is left unknown on how specific micro- and macroscopic structural features affect conduction and conduction block. Progress in this field is constrained by the inability to simultaneously assess intramural cardiac structure and function, as well as the intrinsic complexity and variability of intact tissue preparations. Cultured monolayers of cardiac cells, on the other hand, present a well-controlled in vitro model system that provides the necessary structural and functional simplifications to enable well-defined studies of electrical phenomena. In this thesis, I developed a novel, reproducible cell culture system that accurately replicates the realistic microstructure of cardiac tissues. This system was then applied to systematically explore the influence of natural structure (e.g. tissue boundaries, expansions, local fiber directions) on normal and arrhythmogenic electrical conduction.</p><p>Specifically, soft lithography techniques were used to design cell cultures based on microscopic DTMRI (diffusion tensor magnetic resonance imaging) measurements of fiber directions in murine ventricles. Protein micropatterns comprised of mosaics of square pixels with angled lines that followed in-plane cardiac fiber directions were created to control the adhesion and alignment of cardiac cells on a two-dimensional substrate. The high accuracy of cell alignment in the resulting micropatterned monolayers relative to the original DTMRI-measured fiber directions was validated using immunofluorescence and image processing techniques.</p><p>Using this novel model system, I first examined how specific structural features of murine ventricles influence basic electrical conduction. (1) Realistic ventricular tissue boundaries, either alone or with (2) microscopic fiber directions were micropatterned to distinguish their individual functional roles in action potential propagation. By optically mapping membrane potentials and applying low-rate pacing from multiple sites in culture, I found that ventricular tissue boundaries and fiber directions each shaped unique spatial patterns of impulse propagation and additively increased the spatial dispersion of conduction velocity.</p><p>To elucidate the roles that natural tissue structure play in arrhythmogenesis, I applied rapid-rate pacing from multiple sites in culture in an attempt to induce unidirectional conduction block remote from the pacing site--a precursor to reentry. The incidence of remote block was found to be highly dependent on the direction of wave propagation relative to the underlying tissue structure, and with a susceptibility that was synergistically increased by both realistic tissue boundaries and fiber directions. Furthermore, all instances of remote block in these micropatterned cultures occurred at the anterior and posterior junctions of the septum and right ventricular free wall. At these sites, rapid excitation yielded more abrupt conduction slowing and promoted wavefront-waveback interactions that ultimately evolved into transmural lines of conduction block. The location and shape of these lines of block was found to strongly correlate with the spatial distribution of the electrotonic source-load mismatches introduced by ventricular structures, such as tissue expansions and sharp turns in fiber direction.</p><p>In summary, the overall objective of the work described in this thesis was to reveal the distinct influences of realistic cardiac tissue structure on action potential conduction and conduction block by engineering neonatal rat cardiomyocyte monolayers that reproducibly replicated the anatomical details of murine ventricular cross-sections. In the future, this novel model system is expected to further our understanding of structure-function relationships in normal and structurally diseased hearts, and possibly enable the development of novel gene, cell, and ablation therapies for cardiac arrhythmias.</p>Dissertatio

Assessing hemodynamic response to submaximal exercise in pulmonary arterial hypertension patients using an implantable hemodynamic monitor.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease that is incurable, even with effective therapy. Long-term outcome in PAH is best preserved by targeting hemodynamic improvements to reduce risk of subsequent right ventricular (RV) failure. Methods that can assess RV adaptation to stress have important implications to better understand an individual\u27s physiology and may play a pivotal role in guiding therapy in PAH. In this novel pilot study, we evaluate the feasibility of monitoring hemodynamic response to 6-minute walk distance in patients with PAH using the CardioMEMS HF System

Identification and Determination of Drug Resistant of Candida species isolated from Hospital Acquired Infections

Background & aim: Currently, the use of antifungal azole group and yeasts resistant to these drugs is increasing. The aim of this study was to isolate and identify the yeasts obtained from candidiasis patients and furthermore determining thier antifungal resistance. Methods: In the present descriptive study, infections samples were collected from 256 patients with suspected nosocomial candidiasis, then direct exam and culture were performed. Yeast colonies were identified using phenotypic methods, polymerase chain reaction method and enzyme digestion. Data were analyzed using Descriptive statistical tests. Results: Of sixty isolated yeast, thirty-seven cases of Candida albicans (61.6%), seven cases of C. krusei and C. glabrata (11.6%) each, five cases of C. dubliniensis (8.3%) and four cases of C. tropicalis (6.6%) were indicated. The study showed that the sensitivity of C. albicans and C. cruise species to amphotericin B was negligible in disk diffusion and very sensitve in microdilution. Conclusion: Inspite of the results of antifungal susceptibility test of strains studied did not show high resistance, but screening for drug-resistant Candida isolates in Candida infection by disk diffusion and microdilution methods for new cases of drug resistance is reasonable

Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint Pacing: A feasibility study of noninvasive hemodynamics–guided device programming

International audienceBackgroundCardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint Pacing [MPP]) improves acute hemodynamics and chronic outcomes in comparison to conventional biventricular pacing (BiV), though MPP programming questions persist.ObjectivesIn this multicenter feasibility study, we evaluated the feasibility of using noninvasive systolic blood pressure (SBP) to guide MPP programming and assessed the chronic 6-month echocardiographic CRT response.MethodsPatients implanted with MPP-enabled CRT-defibrillator devices underwent noninvasive hemodynamic assessment (finger arterial pressure) during a pacing protocol that included atrial-only pacing and various BiV and MPP configurations. Each configuration was repeated 4 times, alternating with a reference pacing configuration, to calculate the SBP difference relative to reference (ΔSBP). CRT configurations with the greatest ΔSBP were programmed. An independent core laboratory analyzed baseline and 6-month echocardiograms, with CRT response defined as a 6-month reduction in LV end-systolic volume ≥ 15%.ResultsForty-two patients (71% male; LV ejection fraction 30.3% ± 7.5%; QRS duration 161 ± 19 ms; 26% had ischemic cardiomyopathy) were enrolled in 4 European centers. Relative to atrial-only pacing, the best BiV and best MPP configurations produced significant SBP elevations of 3.1 ± 4.2 (P < .01) and 4.1 ± 4.1 mm Hg (P < .01), respectively (BiV vs MPP; P < .01). Greater SBP elevations were associated with the best MPP compared with the best BiV configurations in 29 of 37 patients completing the pacing protocol (78%). Of MPP-programmed patients completing the 6-month follow-up visit, 23 of 27 (85%) were classified as CRT responders (6-month reduction in LV end-systolic volume 37.0% ± 13.6%).ConclusionAcute noninvasive hemodynamics after CRT device implantation predominantly favored MPP over BiV programming. MPP programming guided by noninvasive hemodynamics resulted in positive LV structural remodeling