Publications by authors named "Christian Steinberg"

183 Publications

Variant Re-interpretation in Survivors of Cardiac Arrest with Preserved Ejection Fraction (CASPER Registry) by Clinicians and Clinical Commercial Laboratories.

Circ Genom Precis Med 2021 May 7. Epub 2021 May 7.

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

- Following an unexplained cardiac arrest, clinical genetic testing is increasingly becoming standard of care. Periodic review of variant classification is required, as re-interpretation can change the diagnosis, prognosis, and management of patients and their relatives. - This study aimed to develop and validate a standardized algorithm to facilitate clinical application of the 2015 American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) guidelines for the interpretation of genetic variants. The algorithm was applied to genetic results in the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER), to assess the rate of variant re-classification over time. Variant classifications were then compared to the classifications of two commercial laboratories to determine the rate and identify sources of variant interpretation discordance. - Thirty-one percent of participants (40/131) had at least one genetic variant with a clinically significant reclassification over time. Variants of uncertain significance were more likely to be downgraded (73%) to benign than upgraded to pathogenic (27%, p= 0.03). For the second part of the study, 50% (70/139) of variants had discrepant interpretations (excluding benign variants), provided by at least one team. - Periodic review of genetic variant classification is a key component of follow-up care given rapidly changing information in the field. There is potential for clinical care gaps with discrepant variant interpretations, based in the interpretation and application of current guidelines. The development of gene and disease specific guidelines and algorithms may provide an opportunity to further standardize variant interpretation reporting in the future.
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http://dx.doi.org/10.1161/CIRCGEN.120.003235DOI Listing
May 2021

Metatranscriptomic comparison of endophytic and pathogenic Fusarium-Arabidopsis interactions reveals plant transcriptional plasticity.

Mol Plant Microbe Interact 2021 Apr 15. Epub 2021 Apr 15.

University of Massachusetts Amherst, Biochemistry and Molecular Biology, 240 Thatcher Road, Amherst, Amherst, Massachusetts, United States, 01003;

Plants are continuously exposed to beneficial and pathogenic microbes, but how plants recognize and respond to friends versus foes remains poorly understood. Here, we compared the molecular response of independently challenged with a endophyte Fo47 versus a pathogen Fo5176. These two strains share a core genome of about 46 Mb, in addition to unique 1,229 and 5,415 accessory genes. Metatranscriptomic data reveal a shared pattern of expression for most plant genes (~80%) in responding to both fungal inoculums at all time points from 12 to 96 h post inoculation (HPI). However, the distinct responding genes depict transcriptional plasticity, as the pathogenic interaction activates plant stress responses and suppresses plant growth/development related functions, while the endophytic interaction attenuates host immunity but activates plant nitrogen assimilation. The differences in reprogramming of the plant transcriptome are most obvious in 12 HPI, the earliest time point sampled and are linked to accessory genes in both fungal genomes. Collectively, our results indicate that the and interaction displays both transcriptome conservation and plasticity in the early stages of infection, providing insights into the fine-tuning of gene regulation underlying plant differential responses to fungal endophytes and pathogens.
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http://dx.doi.org/10.1094/MPMI-03-21-0063-RDOI Listing
April 2021

Defining idiopathic ventricular fibrillation: A systematic review of diagnostic testing yield in apparently unexplained cardiac arrest.

Heart Rhythm 2021 Mar 26. Epub 2021 Mar 26.

Center for Cardiovascular Innovation, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with apparently unexplained cardiac arrest (UCA) after varying degrees of evaluation. This is largely due to the lack of a standardized approach to UCA.

Objective: We sought to develop an evidence-based diagnostic algorithm for IVF by systematically examining the yield of diagnostic testing in UCA probands.

Methods: Studies reporting the yield of diagnostic testing in UCA were identified in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and conference abstracts. Their methodological quality was assessed by the National Institutes of Health quality assessment tool. Meta-analyses were performed using the random effects model.

Results: A total of 21 studies were included. The pooled comprehensive diagnostic testing yield was 43% (95% confidence interval 39%-48%). A lower yield was seen when only definite diagnoses based on the prespecified criteria were used (32% vs 47%; P = .15). Epinephrine challenge, Holter monitoring, and family screening were associated with low yield (<5%), whereas cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge were associated with high yield (≥5%). Coronary spasm provocation, electrophysiology study, and systematic genetic testing were reported to be abnormal in a high proportion of UCA probands (>10%).

Conclusion: We developed a stepwise algorithm for UCA evaluation and criteria to assess the strength of IVF diagnosis on the basis of the diagnostic yield of UCA testing.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.030DOI Listing
March 2021

Twiddler Syndrome without Lead Dislodgment Discovered by Remote Monitoring.

Case Rep Cardiol 2021 6;2021:8816524. Epub 2021 Feb 6.

Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec, Canada.

Twiddler syndrome is an uncommon yet dangerous phenomenon usually resulting in lead displacement with loss of capture of cardiac implantable electronic devices. In this case report, we present an interesting case of Twiddler syndrome without lead dislodgment which was detected by an alert triggered by an increase in impedance on remote monitoring.
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http://dx.doi.org/10.1155/2021/8816524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884166PMC
February 2021

SCN5A-C683R exhibits combined gain-of-function and loss-of-function properties related to adrenaline-triggered ventricular arrhythmia.

Exp Physiol 2021 Mar 5;106(3):683-699. Epub 2021 Feb 5.

IUCPQ-UL Research Center, Laval University, Québec, QC, Canada.

New Findings: What is the role of SCN5A-C683R? SCN5A-C683R is a novel variant associated with an uncommon phenotype of adrenaline-triggered ventricular arrhythmia in the absence of a distinct ECG phenotype. What is the main finding and its importance? Functional studies demonstrated that Na 1.5/C683R results in a mixed electrophysiological phenotype with gain-of-function (GOF) and loss-of-function (LOF) properties compared with Na 1.5/wild type. Gain-of-function properties are characterized by a significant increase of the maximal current density and a hyperpolarizing shift of the steady-state activation. The LOF effect of Na 1.5/C683R is characterized by increased closed-state inactivation. Electrophysiological properties and clinical manifestation of SCN5A-C683R are different from long-QT-3 or Brugada syndrome and might represent a distinct inherited arrhythmia syndrome.

Abstract: Mutations of SCN5Ahave been identified as the genetic substrate of various inherited arrhythmia syndromes, including long-QT-3 and Brugada syndrome. We recently identified a novel SCN5A variant (C683R) in two genetically unrelated families. The index patients of both families experienced adrenaline-triggered ventricular arrhythmia with cardiac arrest but did not show a specific ECG phenotype, raising the hypothesis that SCN5A-C683R might be a susceptibility variant and the genetic substrate of distinct inherited arrhythmia. We conducted functional cellular studies to characterize the electrophysiological properties of Na 1.5/C683R in order to explore the potential pathogenicity of this novel variant. The C683R variant was engineered by site-directed mutagenesis. Na 1.5/wild type (WT) and Na 1.5/C683R were expressed in tsA201 cells. Electrophysiological characterization of C683R was performed using the whole-cell patch-clamp technique. Adrenergic stimulation was mimicked by exposure to the protein kinase A activator 8-CPT-cAMP. The impact of β-blockers was tested by exposing Na 1.5/WT and Na 1.5/C683R currents to propranolol and nadolol. C683R resulted in a co-association of gain-of-function and loss-of-function properties of Na 1.5. Gain-of-function properties were characterized by a significant increase of the maximal Na 1.5 current density compared with Na 1.5/WT (861 ± 309 vs. 627 ± 489 pA/pF; P < 0.05, n ≥ 9) that was potentiated in Na 1.5/C683R with 8-CPT-cAMP stimulation (869 ± 287 vs. 607 ± 320 pA/pF; P < 0.05, n ≥ 12). C683R also resulted in a significant hyperpolarizing shift in the voltage of steady-state activation (-65.4 ± 3.0 vs. -57.2 ± 4.8 mV; P < 0.001), resulting in an increased window current compared with WT. The loss-of-function effect of Na 1.5/C683R was characterized by significantly increased closed-state inactivation compared with Na 1.5/WT (P < 0.05). C683R is a novel SCN5A variant resulting in a co-association of gain-of-function and loss-of-function properties of the cardiac sodium channel Na 1.5. The phenotype is characterized by adrenaline-triggered ventricular arrhythmias. Electrophysiological properties and clinical manifestations are different from long-QT-3 or Brugada syndrome and might represent a distinct inherited arrhythmia syndrome.
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http://dx.doi.org/10.1113/EP089088DOI Listing
March 2021

Phenol-rich fulvic acid as a water additive enhances growth, reduces stress, and stimulates the immune system of fish in aquaculture.

Sci Rep 2021 Jan 8;11(1):174. Epub 2021 Jan 8.

Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, 12587, Germany.

Aquaculture has become imperative to cover the demands for dietary animal protein. Simultaneously, it has to overcome prejudices from excessive use of antibiotics and environmental impacts. Natural supplements are traditionally applied orally. In this study, we demonstrated another pathway: the gills. Humic substances are immunostimulants and a natural part of every aquatic ecosystem, making them ideal to be used as bath stimulants. Five and 50 mg C/L of a fulvic acid-rich humic substance was added for 28 days to the water of juvenile rainbow trout (Oncorhynchus mykiss). This fulvic acid is characterized by a high content of phenolic moieties with persistent free radicals and a high electron exchange capacity. The high concentration of the fulvic acid significantly increased growth and reduced the food conversion ratio and the response to a handling-stressor. Phagocytosis and potential killing activity of head kidney leukocytes were increased, as well as the total oxyradical scavenging capacity (TOSC) and lysozyme activity in the gills. In conclusion, immunostimulation via gills is possible with our fulvic acid, and the high phenolic content improved overall health and stress resistance of fish.
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http://dx.doi.org/10.1038/s41598-020-80449-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794407PMC
January 2021

The Hearts in Rhythm Organization: A Canadian National Cardiogenetics Network.

CJC Open 2020 Nov 29;2(6):652-662. Epub 2020 May 29.

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background: The Hearts in Rhythm Organization (HiRO) is a team of Canadian inherited heart rhythm and cardiomyopathy experts, genetic counsellors, nurses, researchers, patients, and families dedicated to the detection of inherited arrhythmias and cardiomyopathies, provision of best therapies, and protection from the tragedy of sudden cardiac arrest.

Methods: Recently, existing disease-specific registries were merged into the expanded National HiRO Registry, creating a single common data set for patients and families with inherited conditions that put them at risk for sudden death in Canada. Eligible patients are invited to participate in the registry and optional biobank from 20 specialized cardiogenetics clinics across Canada.

Results: Currently, there are 4700 participants enrolled in the National HiRO Registry, with an average of 593 participants enrolled annually over the past 5 years. The capacity to enable knowledge translation of research findings is built into HiRO's organizational infrastructure, with 3 additional working groups (HiRO Clinical Care Committee, HiRO Active Communities Committee, and HiRO Annual Symposium Committee), supporting the organization's current goals and priorities as set alongside patient partners.

Conclusion: The National HiRO Registry aims to be an integrated research platform to which researchers can pose novel research questions leading to a better understanding, detection, and clinical care of those living with inherited heart rhythm and cardiomyopathy conditions and ultimately to prevent sudden cardiac death.
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http://dx.doi.org/10.1016/j.cjco.2020.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710951PMC
November 2020

Application of low dosage of copper oxide and zinc oxide nanoparticles boosts bacterial and fungal communities in soil.

Sci Total Environ 2021 Feb 26;757:143807. Epub 2020 Nov 26.

Institute of Environmental Sciences (CML), Leiden University, Leiden 2300, RA, the Netherlands; National Institute of Public Health and the Environment (RIVM), Center for Safety of Substances and Products, Bilthoven 3720 BA, the Netherlands.

With the expanding nanotechnology, nanoparticles (NPs) embedded products are used in the agricultural sector to improve soil fertility. Thus, two typical metal oxides NPs and their mixtures were applied in different doses to evaluate the impacts on soil microbes. CuO and ZnO NPs boosted soil microbial communities as reflected by the increased number of extractable bacterial or fungal groups and the enlarged values of Chao 1, ACE, and Shannon indices. Relative abundance of some susceptible taxa such as Sphingomonadales increased with increasing concentrations of ZnO NPs, while IMCC26256 decreased with increasing concentrations of CuO NPs. The mixture of CuO and ZnO NPs did not show more promotional effects on the soil bacterial community than the sum of individual effects. Increased soil organic carbon mitigated the impacts on soil bacteria for CuO NPs, but not for ZnO NPs. As micro-nutrients, the ions released from CuO and ZnO NPs had the potential to promote soil microbial community richness and diversity. However, the positive impacts of MNPs were impaired at dosage higher than 250 mg kg soil (213.08 mg kg soil of Cu, 162.73 mg kg soil of Zn). Thus, the application dose and soil type other than the coexistence of MNPs should be considered before the wide use in increasing agricultural productivity.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143807DOI Listing
February 2021

Reaction of Substituted Phenols with Lignin Char: Dual Oxidative and Reductive Pathways Depending on Substituents and Conditions.

Environ Sci Technol 2020 12 26;54(24):15811-15820. Epub 2020 Nov 26.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, Massachusetts 01003, United States.

Biomass chars are known to be intrinsically redox-reactive toward some organic compounds, but the mechanisms are still unclear. To address this, a char made anoxically at 500 °C from dealkaline lignin was reacted either in the fresh state or after 180-day aging in air with -nitrophenol (NO-P), -hydroxybenzaldehyde (CHO-P), phenol (H-P), or -methoxyphenol (MeO-P). The reactions were carried out under oxic or anoxic conditions. Degradation occurred in all cases. Both oxidation and reduction products were identified, with yields dependent on the presence or absence of air during reaction or storage. They included oligomers, amines, and ring-hydroxylated compounds, among others. Exposure to air suppressed sorption, annihilated reducing sites, and provided a source of reactive oxygen species that assisted degradation. Sorption suppression was due to the incorporation of hydrophilic groups by chemisorption of oxygen, and possibly blockage of sites by products. Fresh char has comparable electron-donating and accepting capacity, whereas there is a preponderance of electron-accepting over donating capacity in aged char. Under anoxic conditions, both oxidation and reduction occurred. Under oxic conditions or after aging in air, oxidation predominated, and linear free energy relationships were found between the rate constant and the Hammett or Brown substituent electronic parameter or the standard electrode potential of the phenol. The results demonstrate that chars possess heterogeneous redox activities depending on reaction pairs, reaction conditions, and aging.
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http://dx.doi.org/10.1021/acs.est.0c04991DOI Listing
December 2020

Phylogenomic analysis of a 55.1 kb 19-gene dataset resolves a monophyletic Fusarium that includes the Fusarium solani Species Complex.

Phytopathology 2020 Nov 17. Epub 2020 Nov 17.

University of Cordoba, Genetics, Campus Rabanales, Edif. C5, Cordoba, Spain, 14071;

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. Previously (Geiser et al. 2013; Phytopathology 103:400-408. 2013), the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani Species Complex (FSSC). Subsequently, this concept was challenged by one research group (Lombard et al. 2015 Studies in Mycology 80: 189-245) who proposed dividing Fusarium into seven genera, including the FSSC as the genus Neocosmospora, with subsequent justification based on claims that the Geiser et al. (2013) concept of Fusarium is polyphyletic (Sandoval-Denis et al. 2018; Persoonia 41:109-129). Here we test this claim, and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species recently described as Neocosmospora were recombined in Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural and practical taxonomic option available.
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http://dx.doi.org/10.1094/PHYTO-08-20-0330-LEDOI Listing
November 2020

Ventricular Arrhythmia in Septal and Apical Hypertrophic Cardiomyopathy: The French-Canadian Experience.

Front Cardiovasc Med 2020 22;7:548564. Epub 2020 Oct 22.

Division of Cardiology, Multidisciplinary Cardiovascular Department, Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ-UL), Université Laval, Québec City, QC, Canada.

Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients ( = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.
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http://dx.doi.org/10.3389/fcvm.2020.548564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642600PMC
October 2020

The contrasting role of minerals in biochars in bisphenol A and sulfamethoxazole sorption.

Chemosphere 2021 Feb 3;264(Pt 1):128490. Epub 2020 Oct 3.

Faculty of Environment Science & Engineering, Kunming University of Science & Technology, Kunming, Yunnan, 650500, China; Faculty of Life Sciences, Institute of Biology, Freshwater & Stress Ecology, Humboldt-University at Berlin, Arboret Späthstr. 80/81, 12437, Berlin, Germany.

Biochars are one of carbon-rich substances that have attracted enormous attention because of its values in energy storage, carbon sequestration, and environment remediation. Apart from the carbon structure, biochars also contain inherent mineral component and polar functional groups. However, the importance of the inherent minerals to the stability of biochars as well as the sorption of organic compounds remains unclear. In this work, the demineralized treatment by the hydrofluoric acid was employed to remove the inorganic minerals from biochars produced at 300 and 500 °C. The inorganic minerals in biochars were identified and quantified by XRD, XPS and SEM-EDS techniques. Approximately 75% of biochar minerals belonged to the Si- and Al-containing minerals, which connected with carbon skeletons. The impact of these minerals to bisphenol A (BPA) and sulfamethoxazole (SMX) sorption was investigated. The mineral removal decreased BPA sorption but increased SMX sorption. Moreover, the relative contributions of surface adsorption and partition processes were quantified for both compounds through isotherm modeling. The BPA sorption was regulated by the joint effect of adsorption and partition, while more than 82% of the SMX sorption was dominated by the partition process. Such understanding of biochar minerals and carbon structure to the migration of organic contaminants will benefit biochar production and application.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128490DOI Listing
February 2021

Findings of remote monitoring of implantable cardioverter defibrillators during the COVID-19 pandemic.

Pacing Clin Electrophysiol 2020 11 26;43(11):1366-1372. Epub 2020 Oct 26.

Department of Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada.

Background: Monitoring of cardiac implantable electronic devices was highly impacted by the COVID-19 pandemic considering the high volume of in-person visits for regular follow-up. Recent recommendations highlight the important role of remote monitoring to prevent exposure to the virus. This study compared remote monitoring of implantable cardioverter defibrillators (ICDs) in patients whose in-person annual visit was substituted for a remote monitoring session with patients who were already scheduled for a remote monitoring session.

Methods: This was a cross-sectional observational study of 329 consecutive patients between 20 March and 24 April 2020. Group 1 included 131 patients whose in-person annual visit was substituted for a remote monitoring session. Group 2 included 198 patients who underwent a remote monitoring session as scheduled in their usual device follow-up. The time interval since the last in-person visit was 13.3 ± 3.2 months in group 1 and 5.9 ± 1.7 months in group 2 (P < .01).

Results: In group 1, 15 patients (11.5%) experienced a clinical event compared to 15 patients (7.6%) in group 2 (P = .25). Nineteen patients (14.5%) required a physician intervention in group 1 compared to 19 patients (9.6%) in group 2 (P = .22). Two patients (1.5%) in group 1 and four patients (2.0%) in group 2 required an early in-person follow-up visit during the pandemic (P > .99).

Conclusion: Remote monitoring of ICDs is useful to identify clinical events and allows physicians to treat patients appropriately during the COVID-19 pandemic regardless of the time interval since their last in-person visit. It reduces significantly in-person visit for regular follow-up.
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http://dx.doi.org/10.1111/pace.14086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675613PMC
November 2020

Can the properties of engineered nanoparticles be indicative of their functions and effects in plants?

Ecotoxicol Environ Saf 2020 Dec 19;205:111128. Epub 2020 Aug 19.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, MA, 01003, United States. Electronic address:

The extensive applicability of engineered nanoparticles (ENPs) in various fields such as environment, agriculture, medicine or biotechnology has mostly been attributed to their better physicochemical properties as compared with conventional bulk materials. However, functions and biological effects of ENPs change across different scenarios which impede the progress in their risk assessment and safety management. This review thus intends to figure out whether properties of ENPs can be indicators of their behavior through summarizing and analyzing the available literature and knowledge. The studies have indicated that size, shape, solubility, specific surface area, surface charge and surface reactivity constitute a more accurate measure of ENPs functions and toxic effects in addition to mass concentration. Effects of ENPs are also highly dependent on dose metrics, species and strains of organisms, environmental conditions, exposure route and duration. Searching correlations between properties and functions or biological effects may serve as an effective way in understanding positive and negative impacts of ENPs. This will ensure safe design and sustainable future use of ENPs.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111128DOI Listing
December 2020

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of -Catecholaminergic Polymorphic Ventricular Tachycardia.

Circulation 2020 Sep 22;142(10):932-947. Epub 2020 Jul 22.

Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada (K.N., J.W., A.S.T., A.C.S., J.M., J.D.R.).

Background: Genetic variants in calsequestrin-2 () cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of -CPVT was sought through an international multicenter collaboration.

Methods: Genotype-phenotype segregation in -CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure.

Results: A total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic variant, were identified. Among homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to heterozygotes, homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; =0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; <0.001) increased hazard in genotype-positive family members. In vitro turbidity assays revealed that p.R33Q and all 6 candidate dominant missense variants evaluated exhibited filamentation defects, but only p.R33Q convincingly failed to dimerize. Structural analysis revealed that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket considered critical for back-to-back binding of dimers.

Conclusions: This international multicenter study of -CPVT redefines its heritability and confirms that pathogenic heterozygous variants may manifest with a CPVT phenotype, indicating a need to clinically screen these individuals. A dominant mode of inheritance appears intrinsic to certain missense variants because of their location and function within the CASQ2 filament structure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484339PMC
September 2020

Chromosome-Scale Genome Assembly of Strain Fo47, a Fungal Endophyte and Biocontrol Agent.

Mol Plant Microbe Interact 2020 Sep 28;33(9):1108-1111. Epub 2020 Jul 28.

MOE Key Laboratory for Intelligent Networks & Network Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

Here, we report a chromosome-level genome assembly of Fo47 (12 pseudomolecules; contig N: 4.52 Mb), generated using a combination of PacBio long-read, Illumina paired end, and high-throughput chromosome conformation capture sequencing data. Although causes vascular wilt to over 100 plant species, the strain Fo47 is classified as an endophyte and is widely used as a biocontrol agent for plant disease control. The Fo47 genome carries a single accessory chromosome of 4.23 Mb, compared with the reference genome of f. sp. Fol4287. The high-quality assembly and annotation of the Fo47 genome will be a valuable resource for studying the mechanisms underlying the endophytic interactions between and plants as well as for deciphering the genome evolution of the species complex.
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http://dx.doi.org/10.1094/MPMI-05-20-0116-ADOI Listing
September 2020

Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) Study.

Can J Cardiol 2020 08 28;36(8):1269-1277. Epub 2020 May 28.

Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary-prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of this study was to assess the incidence of ICD therapies at 30, 60, and 180 days after implantation.

Methods: Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) was a retrospective cohort study conducted at 2 Canadian university centres enrolling patients with new implantation of a primary-prevention ICD. Device programming was standardised according to current guidelines. A total of 803 patients were enrolled.

Results: The cumulative rates of appropriate ICD therapies at 30, 60, and 180 days were 0.12%, 0.50%, and 0.75%, respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, < 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation.

Conclusions: The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary-prevention ICD recipients.
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http://dx.doi.org/10.1016/j.cjca.2020.05.029DOI Listing
August 2020

Clinical assessment of AF pattern is poorly correlated with AF burden and post ablation outcomes: A CIRCA-DOSE sub-study.

J Electrocardiol 2020 May - Jun;60:159-164. Epub 2020 Mar 21.

Montreal Heart Institute, Department of Medicine, Université de Montréal, Canada.

Background: Contemporary guidelines recommend that atrial fibrillation (AF) be classified into paroxysmal and persistent AF based on clinical assessment, with these categorizations forming the basis of therapeutic recommendations. While pragmatic, clinical assessment may introduce misclassification errors, which may impact treatment decisions. We sought to determine the relationship between AF classification, baseline AF burden, and post-ablation arrhythmia outcomes.

Design: The current study is a sub-analysis of a prospective, parallel-group, multicenter, single-blinded randomized clinical trial. All 346 patients enrolled in CIRCA-DOSE received an implantable cardiac monitor a median of 72 days prior to ablation. AF was classified as low burden paroxysmal, high burden paroxysmal, or persistent based on clinical assessment prior to device implantation. Prior to ablation patients were re-classified using the same definitions based on device monitoring data. Correlation between classifications, AF burden, and post-ablation arrhythmia outcomes were assessed.

Results: There was poor agreement between clinical and device-based AF classification (Cohen's kappa: 0.192). AF classification derived from pre-ablation continuous monitoring reflected baseline and post-ablation AF burden with greater accuracy and with less overlap between the AF classes (P < 0.01 for all categorical comparisons). Patients objectively classified as "Low Burden" paroxysmal by continuous monitoring data had significantly greater freedom from recurrent AF/AT/AFL compared to those classified as "High Burden" paroxysmal (hazard ratio [HR] 0.57 for AF/AT/AFL recurrence) or persistent AF (HR 0.19 for AF/AT/AFL recurrence).

Conclusions: Classification of AF pattern based on pre-ablation continuous cardiac rhythm monitoring better predicted AF burden and freedom from recurrent AF post ablation. Despite the use of standardized definitions, classification of AF based on clinical assessment did not predict baseline AF burden, post ablation AF burden, or freedom from recurrent AF post ablation.

Trial Registration: ClinicalTrials.govNCT01913522.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.03.008DOI Listing
March 2020

Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society.

Can J Cardiol 2020 06 8;36(6):948-951. Epub 2020 Apr 8.

University of British Columbia, Vancouver, British Columbia, Canada.

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.
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http://dx.doi.org/10.1016/j.cjca.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195336PMC
June 2020

Organo-mineral complexes protect condensed organic matter as revealed by benzene-polycarboxylic acids.

Environ Pollut 2020 May 13;260:113977. Epub 2020 Jan 13.

Stockbridge School of Agriculture, University of Massachusetts, Amherst, MA, 01003, United States.

Condensed organic matters (COM) with black carbon-like structures are considered as long-term carbon sinks because of their high stability. It is difficult to distinguish COM from general organic matter by conventional chemical analysis, thus the contribution by and interaction mechanisms of organo-mineral complexes in COM stabilization are unclear and generally neglected. Molecular markers related to black carbon-like structures, such as benzene polycarboxylic acids (BPCAs), are promising tools for the qualitative and quantitative analysis of COM. In this study, one natural soil and two cultivated soils with 25 y- or 55 y-tillage activities were collected and the distribution characteristics of BPCAs were detected. All the investigated soils showed similar BPCA distribution pattern, and over 60% of BPCAs were detected in clay fraction. The extractable BPCA contents were substantially increased after mineral removal. The ratios of BPCA contents before and after mineral removal indicate the extent of COM-mineral particle interactions, and our results suggested that up to 73% COM were protected by mineral particles, and more stronger interactions were noted on clay than on silt. The initial cultivation dramatically decreased COM-clay interactions, and this interaction was recovered only slowly after 55-y cultivation. Kaolinite and muscovite are important for COM protection. But a possible negative correlation between BPCAs and reactive iron oxides of the cultivated soils suggested that iron may promote COM degradation when disturbed by tillage activities. This study provided a new angle to study the stabilization of COM and emphasized the importance of organo-mineral complexes for COM stabilization.
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http://dx.doi.org/10.1016/j.envpol.2020.113977DOI Listing
May 2020

Orthodromic atrioventricular reentrant tachycardia using a concealed isoproterenol-sensitive accessory pathway.

Indian Pacing Electrophysiol J 2020 Mar - Apr;20(2):73-77. Epub 2019 Dec 16.

Electrophysiology Division - Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Laval University, Canada.

Accessory pathways (APs) represent the substrate for atrioventricular reentrant tachycardia. Catecholamine-sensitivity is an uncommon feature of APs and has been almost exclusively been described in APs with antegrade conduction. We present the rare case of a catecholamine-dependent concealed AP that was only unmasked upon isoproterenol stimulation and successfully ablated. This case highlights the importance of systematic isoproterenol stimulation in patients referred for ablation of supraventricular tachycardia - in particular if the baseline electrophysiology study is negative. Otherwise, ablation targets may be missed. LEARNING OBJECTIVE: The absence of retrograde ventriculo-atrial conduction does not automatically exclude the presence of a concealed accessory pathway. Systematic isoproterenol stimulation should be part of any electrophysiology study for supraventricular tachycardia, to search for catecholamine-sensitive accessory pathways that may be otherwise missed.
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http://dx.doi.org/10.1016/j.ipej.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082688PMC
December 2019

Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial.

Circulation 2019 11 21;140(22):1779-1788. Epub 2019 Oct 21.

Montreal Heart Institute, Department of Medicine, Université de Montréal, Montreal, Canada (J.G.A., M.D., L.M., P.K.).

Background: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation.

Methods: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder.

Results: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively (=0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively (=0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%-100.0%) with CF-RF, 99.9% (interquartile range, 65.3%-100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%-100.0%) with Cryo-2 (=0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups (=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (<0.001 vs cryoballoon groups).

Conclusions: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913522.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042622DOI Listing
November 2019

Caseous Calcification of the Mitral Annulus: A Role for Surgery.

Ann Thorac Surg 2020 06 10;109(6):e441-e444. Epub 2019 Oct 10.

Service of Cardiac Surgery, Institut de cardiologie et de pneumologie de Québec (IUCPQ)-Université Laval, Quebec City, Quebec, Canada. Electronic address:

An 80-year-old man followed for aortic stenosis was found to have an intracardiac mass. Multiple imaging modalities were inconclusive in characterizing the mass but raised concerns about the potential malignancy of the mass. Fear of operating on an elderly patient with a potential for cardiac neoplasia led to a percutaneous transseptal biopsy that failed to provide a clear diagnosis. Cardiac valvular surgery was performed in addition to excisional biopsy of the mass that turned out to be caseous necrosis of mitral annular calcifications.
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http://dx.doi.org/10.1016/j.athoracsur.2019.08.110DOI Listing
June 2020

Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site.

Europace 2019 Nov;21(11):1725-1732

Division of Cardiology, University of British Columbia, 1033 Davie St., Rm 211, Vancouver, BC, Canada.

Aims: Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits.

Methods And Results: Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II-III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II-III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II-III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise.

Conclusion: The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II-III loop. This represents a 'mutation hotspot' in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.
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http://dx.doi.org/10.1093/europace/euz215DOI Listing
November 2019

Changes on the electrocardiogram in anorexia nervosa: A case control study.

J Electrocardiol 2019 Sep - Oct;56:64-69. Epub 2019 Jul 8.

Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, 220-1033 Davie St, Vancouver, British Columbia V6E 1M5, Canada. Electronic address:

Purpose: Anorexia nervosa is a complex psychiatric condition with increased mortality. The electrocardiogram (ECG) may show repolarization changes which may associate with an increased risk of sudden death. Up to 80% of patients may be prescribed psychopharmacotherapies which alter the ECG, potentially compounding arrhythmic risk. This study aimed to describe and improve understanding of ECG changes in eating disorders and assess the effect of psychopharmacotherapies.

Methods: Adolescent patients diagnosed with anorexia nervosa were reviewed. ECGs were reviewed by blinded expert reviewers, and repolarization parameters were compared to healthy controls. Patients on and off psychopharmacotherapies were compared.

Results: Thirty-eight anorexia nervosa patients off psychopharmacotherapies were age matched to 53 healthy controls. Heart rate was lower in anorexia nervosa patients (56 vs. 74 bpm, p < 0.001). The absolute QT interval was longer in patients compared to controls (408 vs. 383 ms, p < 0.001), but the QTc by Hodges' formula was similar between groups (401 vs. 408 ms, p = 0.16). The prevalence of T-wave flattening and inversion was also similar between groups (13% vs. 4%, p = 0.12) and T-peak to T-end interval (Tpe) was shorter in patients compared to controls (p < 0.01). ECG parameters were similar between patients on and off psychopharmacotherapies aside from off-drug patients showing lower HR (56 vs. 65, p = 0.04).

Conclusions: Autonomic and repolarization changes are evident on the ECG of anorexia nervosa patients, though the QTc interval was in fact similar between groups. Changes in T-wave morphology and duration may be promising metrics of repolarization effects of anorexia nervosa.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.07.006DOI Listing
July 2019

The relative importance of different carbon structures in biochars to carbamazepine and bisphenol A sorption.

J Hazard Mater 2019 07 19;373:106-114. Epub 2019 Mar 19.

Faculty of Life Sciences, Institute of Biology, Freshwater & Stress Ecology, Humboldt-University at Berlin, Arboretum, Späthstr. 80/81, 12437, Berlin, Germany.

Biochar, a carbon-rich material, has attracted immense attention owing to its applications in soil remediation. However, the mechanisms by which heterogeneous carbon structures of biochars immobilize organic contaminants are not yet fully understood. In this study, the noncondensed aromatic components in biochars were selectively removed through bleaching. Different techniques, such as C nuclear magnetic resonance, were applied to characterize the biochar compositions, and thus the role of the different carbon structures in organic contaminant sorption was discussed. The aromatic carbon structures in biochars were gradually developed and evolved from noncondensed to condensed structure with increasing pyrolytic temperatures from 300 to 700 °C. Based on elemental analysis, the carbon removed by bleaching decreased from 43.9% to 5.92% with increasing temperatures. After the surface area normalization of the apparent sorption, bleaching increased the sorption of carbamazepine and bisphenol A on biochars produced at 500 °C, but not for those produced at 300 and 700 °C. Bleaching removed noncondensed aromatics and enriched condensed aromatics, which resulted in increased sorption. However, bleaching also resulted in the blockage of micropores in biochars with abundant condensed aromatics, causing decreased sorption. The apparent sorption was determined by the balancing of these two opposite effects.
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http://dx.doi.org/10.1016/j.jhazmat.2019.03.078DOI Listing
July 2019

Pregnancy in Catecholaminergic Polymorphic Ventricular Tachycardia.

JACC Clin Electrophysiol 2019 03 26;5(3):387-394. Epub 2018 Dec 26.

Heart Rhythm Services, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Objectives: This investigation was a retrospective study of catecholaminergic polymorphic ventricular tachycardia (CPVT) patients in Canada and the Netherlands to compare pregnancy, postpartum, and nonpregnant event rates.

Background: CPVT is characterized by life-threatening arrhythmias during exertion or emotional stress. The arrhythmic risk in CPVT patients during pregnancy is unknown.

Methods: Baseline demographics, genetics, treatment, and pregnancy complications were reviewed. Event rate calculations assumed a 40-week pregnancy and 24-week postpartum period.

Results: Ninety-six CPVT patients had 228 pregnancies (median 2 pregnancies per patient; range: 1 to 10; total: 175.4 pregnant patient-years). The median age of CPVT diagnosis was 40.7 years (range: 12 to 84 years), with a median follow-up of 2.9 years (range: 0 to 20 years; total 448.1 patient-years). Most patients had pregnancies before CPVT diagnosis (82%). Pregnancy and postpartum cardiac events included syncope (5%) and an aborted cardiac arrest (1%), which occurred in patients who were not taking beta-blockers. Other complications included miscarriages (13%) and intrauterine growth restriction (1 case). There were 6 cardiac events (6%) during the nonpregnant period. The pregnancy and postpartum event rates were 1.71 and 2.85 events per 100 patient-years, respectively, and the combined event rate during the pregnancy and postpartum period was 2.14 events per 100 patient-years. These rates were not different from the nonpregnant event rate (1.46 events per 100 patient-years).

Conclusions: The combined pregnancy and postpartum arrhythmic risk in CPVT patients was not elevated compared with the nonpregnant period. Most patients had pregnancies before diagnosis, and all patients with events were not taking beta-blockers at the time of the event.
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http://dx.doi.org/10.1016/j.jacep.2018.10.019DOI Listing
March 2019

Challenge and Impact of Quinidine Access in Sudden Death Syndromes: A National Experience.

JACC Clin Electrophysiol 2019 03 28;5(3):376-382. Epub 2018 Nov 28.

University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Objectives: This study sought to determine the nature of quinidine use and accessibility in a national network of inherited arrhythmia clinics.

Background: Quinidine is an antiarrhythmic medication that has been shown to be beneficial in select patients with Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation. Because of the low prevalence of these conditions and restricted access to quinidine through a single regulatory process, quinidine use is rare in Canada.

Methods: Subjects prescribed quinidine were identified through the Hearts in Rhythm Organization that connects the network of inherited arrhythmia clinics across Canada. Cases were retrospectively reviewed for patient characteristics, indications for quinidine use, rate of recurrent ventricular arrhythmia, and issues with quinidine accessibility.

Results: In a population of 36 million, 46 patients are currently prescribed quinidine (0.0000013%, age 48.1 ± 16.1 years, 25 are male). Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation constituted a diagnosis in 13 subjects (28%), 6 (13%), and 21 (46%), respectively. Overall, 37 subjects (81%) had cardiac arrest as an index event. After initial presentation, subjects experienced 7.47 ± 12.3 implantable cardioverter-defibrillator shocks prior to quinidine use over 34.3 ± 45.9 months, versus 0.86 ± 1.69 implantable cardioverter-defibrillator shocks in 43.8 ± 41.8 months while on quinidine (risk ratio: 8.7, p < 0.001). Twenty-two patients access quinidine through routes external to Health Canada's Special Access Program.

Conclusions: Quinidine use is rare in Canada, but it is associated with a reduction in recurrent ventricular arrhythmias in patients with Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation, with minimal toxicity necessitating discontinuation. Drug interruption is associated with frequent breakthrough events. Access to quinidine is important to deliver this potentially lifesaving therapy.
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http://dx.doi.org/10.1016/j.jacep.2018.10.007DOI Listing
March 2019

What the Cardiologist Should Know About Mitochondrial Cardiomyopathy?

Can J Cardiol 2019 02 29;35(2):221-224. Epub 2018 Nov 29.

Department of Cardiology, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec City, Quebec, Canada. Electronic address:

Mitochondrial diseases are a heterogeneous group of rare hereditary disorders that may manifest with single organ involvement or as multisystemic disease. The pathophysiology of mitochondrial disease is complex and related to mutations of genes encoding mitochondrial proteins that are crucial to the cellular respiratory chain. Given its almost exclusive aerobic metabolism, the heart is particularly susceptible to mitochondrial dysfunction and commonly involved in mitochondrial disorders. Various clinical presentations are described, making clinical recognition challenging. Some patients may evolve towards the early need for heart transplantation, which emphasizes the importance of appropriate diagnosis and referral to a specialized centre.
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http://dx.doi.org/10.1016/j.cjca.2018.11.018DOI Listing
February 2019

A Novel Wearable Device for Continuous Ambulatory ECG Recording: Proof of Concept and Assessment of Signal Quality.

Biosensors (Basel) 2019 Jan 21;9(1). Epub 2019 Jan 21.

Electrophysiology Division, Institut Universitaire de cardiologie et de pneumologie de Québec, Québec, G1V 4G5, QC, Canada.

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs 93% electrophysiologists rating, = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.
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http://dx.doi.org/10.3390/bios9010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468449PMC
January 2019