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JACC. Clinical Electrophysiology Aug 2022The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient.
BACKGROUND
The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient.
OBJECTIVES
This study sought to improve Brugada syndrome diagnosis by using deep learning (DL) to continuously monitor for Brugada type 1 in 24-hour ambulatory 12-lead ECGs (Holters).
METHODS
A convolutional neural network was trained to classify Brugada type 1. The training cohort consisted of 10-second standard/high precordial leads from 12-lead ECGs (n = 1,190) and 12-lead Holters (n = 380) of patients with definite and suspected Brugada syndrome. The performance of the trained model was evaluated in 2 testing cohorts of 10-second standard/high precordial leads from 12-lead ECGs (n = 474) and 12-lead Holters (n = 716).
RESULTS
DL achieved a receiver-operating characteristic area under the curve of 0.976 (95% CI: 0.973-0.979) in classifying Brugada type 1 from 12-lead ECGs and 0.975 (95% CI: 0.966-0.983) from 12-lead Holters. Compared with cardiologist reclassification of Brugada type 1, DL had similar performance and produced robust results in experiments evaluating scalability and explainability. When DL was applied to consecutive 10-second, clean ECGs from 24-hour 12-lead Holters, spontaneous Brugada type 1 was detected in 48% of patients with procainamide-induced Brugada syndrome and in 33% with suspected Brugada syndrome. DL detected no Brugada type 1 in healthy control patients.
CONCLUSIONS
This novel DL model achieved cardiologist-level accuracy in classifying Brugada type 1. Applying DL to 24-hour 12-lead Holters significantly improved the detection of Brugada type 1 in patients with procainamide-induced and suspected Brugada syndrome. DL analysis of 12-lead Holters may provide a robust, automated screening tool before procainamide challenge to aid in the diagnosis of Brugada syndrome.
Topics: Brugada Syndrome; Deep Learning; Electrocardiography; Humans; Procainamide; Wearable Electronic Devices
PubMed: 35981788
DOI: 10.1016/j.jacep.2022.05.003 -
Turkish Journal of Chemistry 2022Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed...
Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed diseases such as cancer. Identifying these changes is crucial in discovering new biomarkers for the early diagnosis of cancer. One of the main steps of -glycan analysis is to release -glycans from glycoproteins by specific enzymes. The study compares common denaturing agent combinations used in -glycan release methods. In the study, human plasma was used to test the release methods of -glycans containing different detergent combinations. The released -glycans were labeled with the procainamide tag, purified using cellulose-containing solid-phase extraction cartridges, and analyzed by high-performance liquid chromatography-hydrophilic interaction liquid chromatography equipped with fluorescence detection (HPLC-HILIC-FLD). The results showed that the sodium dodecyl sulfate and sodium deoxycholate (SDS + SDC) detergent combination provided the highest average FLD signal areas and intensities in the -glycan analysis. The protocol with SDS resulted in more reproducible average FLD signal areas and intensities. It was also found that the average signal FLD signal areas and intensities of the detected -glycans were reduced when SDS and SDC were used with 1,4-dithiothreitol (DTT) reducing agents. In addition, deglycosylation of glycoproteins with various denaturing agents resulted in relatively minor variation in human plasma -glycosylation profiles.
PubMed: 37529735
DOI: 10.55730/1300-0527.3457 -
Global Heart 2022Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the...
BACKGROUND
Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population.
METHODS
Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene () promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and promoter methylation with incident CVD.
RESULTS
During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03-1.44, = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30-0.82, = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at promoter as a whole was significantly associated with incident CVD ( < 0.05).
CONCLUSIONS
Increased proANP and hypomethylation at promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the gene may participate in the mechanisms of CVD.
Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; China; DNA Methylation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptides; Procainamide; Promoter Regions, Genetic
PubMed: 35586748
DOI: 10.5334/gh.1116 -
Experimental Physiology Aug 2022What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be...
NEW FINDINGS
What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be approximated by specific changes on an electrocardiogram (ECG)? What are the main finding and its importance? The triangulation of the ventricular action potential seen when antiarrhythmic drugs induce a greater lengthening of the late repolarization compared to the initial repolarization in epicardium is closely approximated by a greater prolongation of the T wave upslope relative to the interval between the J point and the start of the T wave (the JT interval) on the ECG. These findings may improve the power of ECG assessments in predicting the drug-induced arrhythmia resulting from slowed phase 3 repolarization.
ABSTRACT
Antiarrhythmic drugs prescribed to treat atrial fibrillation can occasionally precipitate ventricular tachyarrhythmia through a prominent slowing of the phase 3 repolarization. The latter results in the triangular shape of ventricular action potential, indicating high arrhythmic risk. However, clinically, the utility of triangulation assessments for predicting arrhythmia is limited owing to the invasive nature of the ventricular action potential recordings. This study examined whether the triangulation effect can be detected indirectly from electrocardiogram (ECG) analysis. Epicardial monophasic action potentials and the ECG were simultaneously recorded in perfused guinea-pig hearts. With antiarrhythmics (dofetilide, quinidine, procainamide and flecainide), a prolongation of the initial repolarization seen in the action potential recordings was closely approximated by lengthening of the interval between the J point and the start of the T wave (the JT interval) on the ECG, whereas a prolongation of the late repolarization was paralleled by widening of the T wave upslope. Dofetilide, quinidine and procainamide induced a prominent slowing of the phase 3 repolarization in epicardium, leading to triangulation of the action potential. These effects were accompanied by a greater prolongation of the T wave upslope compared to the JT interval. Flecainide elicited a proportional prolongation of the initial and the late ventricular repolarization, and therefore failed to induce triangulation, based on analysis of both epicardial action potential and ECG profiles. Collectively, these findings suggest that the ratio between the durations of the T wave upslope and the JT interval may represent the ECG metric of the ventricular action potential triangulation induced by antiarrhythmic drugs.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Electrocardiography; Flecainide; Guinea Pigs; Pericardium; Procainamide; Quinidine
PubMed: 35561081
DOI: 10.1113/EP090349 -
Analytical Chemistry May 2022Sialic acids have diverse biological roles, ranging from promoting up to preventing protein and cellular recognition in health and disease. The various functions of...
Sialic Acid Derivatization of Fluorescently Labeled -Glycans Allows Linkage Differentiation by Reversed-Phase Liquid Chromatography-Fluorescence Detection-Mass Spectrometry.
Sialic acids have diverse biological roles, ranging from promoting up to preventing protein and cellular recognition in health and disease. The various functions of these monosaccharides are owed, in part, to linkage variants, and as a result, linkage-specific analysis of sialic acids is an important aspect of glycomic studies. This has been addressed by derivatization strategies using matrix-assisted laser desorption/ionization mass spectrometry (MS) or sialidase digestion arrays followed by liquid chromatography (LC)-MS. Despite this, these approaches are unable to simultaneously provide unambiguous assignment of sialic acid linkages and assess further isomeric glycan features within a single measurement. Thus, for the first time, we present the combination of procainamide fluorescent labeling with sialic acid linkage-specific derivatization via ethyl esterification and amidation for the analysis of released plasma -glycans using reversed-phase (RP)LC-fluorescence detection (FD)-MS. As a result, α2,3- and α2,6-sialylated -glycans, with the same mass prior to derivatization, are differentiated based on retention time, precursor mass, and fragmentation spectra, and additional sialylated isomers were also separated. Furthermore, improved glycan coverage and protocol precision were found via the novel application using a combined FD-MS quantification approach. Overall, this platform achieved unambiguous assignment of -glycan sialic acid linkages within a single RPLC-FD-MS measurement, and by improving their retention on RPLC, this technique can be used for future investigations of released -glycans as an additional or orthogonal method to current analytical approaches.
Topics: Chromatography, Reverse-Phase; N-Acetylneuraminic Acid; Polysaccharides; Sialic Acids; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35482581
DOI: 10.1021/acs.analchem.1c02610 -
Pediatric Critical Care Medicine : a... Jul 2022To characterize the prevalence, associations, management, and outcomes of supraventricular tachycardia (SVT) in neonates with congenital diaphragmatic hernia (CDH).
OBJECTIVES
To characterize the prevalence, associations, management, and outcomes of supraventricular tachycardia (SVT) in neonates with congenital diaphragmatic hernia (CDH).
DESIGN
Retrospective chart and cardiology code review within a cohort of patients with CDH was used to define a subpopulation with atrial arrhythmia. SVT mechanisms were confirmed by electrocardiogram analysis. Cox proportional hazard regression identified risk factors for SVT and association with clinical outcomes.
SETTING
Medical Surgical ICU in a single, tertiary center, Boston Children's Hospital.
PATIENTS
Eligible patients included neonates presenting with classic Bochdalek posterolateral CDH between 2005 and 2017, excluding newborns with Morgagni hernia or late diagnoses of CDH (>28 d).
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
SVT arose in 25 of 232 neonates with CDH, (11%); 14 of 25 infants (56%) had recurrent SVT; atrioventricular node-dependent tachycardia was the most frequent mechanism (32%). The majority (71%) of SVT episodes received intervention. Nine patients (36%) received preventative antiarrhythmic medications. SVT was associated with lower Apgar score at 1 min, structural heart disease, larger defect size, extracorporeal membrane oxygenation (ECMO) support, and prostaglandin therapy for ductal patency as well as hospital stay greater than or equal to 8 weeks and use of supplemental oxygen at discharge.
CONCLUSIONS
SVT can occur in neonates with CDH and frequently requires treatment. Odds of occurrence are increased with greater CDH disease severity, ECMO, and prostaglandin use. In unadjusted logistic regression analysis, SVT was associated with adverse hospital outcomes, underscoring the importance of recognition and management in this vulnerable population.
Topics: Child; Hernias, Diaphragmatic, Congenital; Humans; Infant; Infant, Newborn; Prevalence; Prostaglandins; Retrospective Studies; Tachycardia, Supraventricular
PubMed: 35353075
DOI: 10.1097/PCC.0000000000002952 -
Analytical Biochemistry Jun 2022Sialylated and core-fucosylated N-glycans in human transferrin (HTF) are used as glycan biomarkers due to their increased or decreased characteristics in certain...
Sialylated and core-fucosylated N-glycans in human transferrin (HTF) are used as glycan biomarkers due to their increased or decreased characteristics in certain diseases. However, their absolute quantities remain unclear. In this study, N-glycans of HTF were identified by UPLC and LC-MS/MS using fluorescence tags [2-aminobenzamide (AB) and procainamide (ProA)] and columns [HILIC and anion exchange chromatography-HILIC (AXH)]. The structures of 14 (including five core-fucosylated) N-glycans in total comprising two non-, six mono-, four di-, and two tri-sialylated N-glycans were identified. The quantities (%) of each N-glycan relative to the total N-glycans (100%) were obtained. HILIC and AXH were better for peak identification and separability except for desialylation, respectively. Specifically, sialylated (in ProA-HILIC and ProA-AXH by UPLC or LC-MS/MS) and core-fucosylated (in AB-HILIC and ProA-AXH by UPLC) N-glycans were efficiently identified. Seven neuraminidase-treated (including three core-fucosylated) N-glycans were efficiently identified in ProA-AXH, even their poor separation. Additionally, ProA-AXH was more efficient for the estimation of the absolute quantities of N-glycans from the results of fluorescence intensity (by UPLC) and relative quantity (by LC-MS/MS). These results first demonstrate that ProA is useful for identifying and quantifying sialylated, core-fucosylated, and neuraminidase-treated desialylated N-glycans in HTF using AXH by UPLC and LC/MS.
Topics: Chromatography, Liquid; Humans; Neuraminidase; Polysaccharides; Tandem Mass Spectrometry; Transferrin
PubMed: 35331694
DOI: 10.1016/j.ab.2022.114650 -
The American Journal of Emergency... May 2022With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac...
BACKGROUND
With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac arrest is limited. We evaluated procainamide for out-of-hospital cardiac arrests (OHCA) from the Resuscitation Outcomes Consortium (ROC).
METHODS
We included all ROC Epistry 3 OHCAs with an initial shockable rhythm that received an antiarrhythmic. We stratified cases by antiarrhythmic: procainamide, amiodarone, or lidocaine. The outcomes were prehospital return of spontaneous circulation (ROSC), ROSC in the ED, and survival to hospital discharge. We defined propensity scores based on possible confounders utilizing 1:1 propensity score matching to compare procainamide to amiodarone and lidocaine. We analyzed the matched data using logistic regression. We also used multivariable logistic regression to evaluate the association between antiarrhythmic and outcomes.
RESULTS
3087 subjects met inclusion criteria; 51 patients received only procainamide, 1776 received amiodarone, and 1418 received lidocaine. On propensity score analysis and compared to procainamide, amiodarone had similar prehospital ROSC (OR 0.7, 95% CI 0.3-1.8), ED ROSC (OR 0.6, 95% CI 0.3-1.3), and survival (OR 1.0, 95% CI 0.3-3.1). Lidocaine also had a similar prehospital ROSC (OR 0.9, 95% CI 0.4-2.2), ED ROSC (OR 1.2, 95% CI 0.5-2.7), and survival (OR 1.4, 95% CI 0.5-4.0). However, using multivariable regression, amiodarone had lower prehospital ROSC than procainamide (aOR 0.3, 95% CI 0.1-0.6).
CONCLUSIONS
While associated with increased prehospital ROSC when compared with amiodarone using multivariable regression, procainamide otherwise had similar prehospital ROSC, ED ROSC, and survival. The role of procainamide in OHCA remains unclear.
Topics: Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Emergency Medical Services; Humans; Lidocaine; Out-of-Hospital Cardiac Arrest; Procainamide; Retrospective Studies
PubMed: 35325787
DOI: 10.1016/j.ajem.2022.02.031 -
Analytical Chemistry Mar 2022Mass spectrometry-based shotgun glycomics (MS-SG) is a rapid, sensitive, label-, and immobilization-free approach for the discovery of natural ligands of glycan-binding...
Mass spectrometry-based shotgun glycomics (MS-SG) is a rapid, sensitive, label-, and immobilization-free approach for the discovery of natural ligands of glycan-binding proteins (GBPs). To perform MS-SG, natural libraries of glycans derived from glycoconjugates in cells or tissues are screened against a target GBP using catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS). Because glycan concentrations are challenging to determine, ligand affinities cannot be directly measured. In principle, relative affinities can be ranked by combining CaR-ESI-MS data with relative concentrations established by hydrophilic interaction liquid chromatography (HILIC) performed on the fluorophore-labeled glycan library. To validate this approach, as well as the feasibility of performing CaR-ESI-MS directly on labeled glycans, libraries of labeled -glycans extracted from the human monocytic U937 cells or intestinal tissues were labeled with 2-aminobenzamide (2-AB), 2-aminobenzoic acid (2-AA), or procainamide (proA). The libraries were screened against plant and human GBPs with known specificities for α2-3- and α2-6-linked sialosides and quantified by HILIC. Dramatic differences, in some cases, were found for affinity rankings obtained with libraries labeled with different fluorophores, as well as those produced using the combined unlabeled/labeled library approach. The origin of these differences could be explained by differential glycan labeling efficiencies, the impact of specific labels on glycan affinities for the GBPs, and the relative efficiency of release of ligands from GBPs in CaR-ESI-MS. Overall, the results of this study suggest that the 2-AB(CaR-ESI-MS)/2-AB(HILIC) combination provides the most reliable description of the binding specificities of GBPs for -glycans and is recommended for MS-SG applications.
Topics: Carrier Proteins; Chromatography, Liquid; Fluorescent Dyes; Glycomics; Humans; Ligands; Polysaccharides; Proteins; Spectrometry, Mass, Electrospray Ionization
PubMed: 35302744
DOI: 10.1021/acs.analchem.1c04779