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Pacing and Clinical Electrophysiology :... Dec 2021Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS)....
BACKGROUND
Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS). Procainamide is a sodium channel blocker used to diagnose BrS. The effects of Procainamide on the SAECG in those with BrS and the significance of Procainamide-induced LPs are unknown.
METHODS
Procainamide provocation was performed for suspected BrS with 12-lead and SAECG pre- and post-infusion. Filtered QRS duration (fQRSd), duration of low amplitude signals <40 μV (LAS40) and root-mean-square voltage in the terminal 40 ms (RMS40) were determined.
RESULTS
Data from 150 patients were included in the analysis (mean age 44.5 years, 109 males). Procainamide increased fQRSd (Pre 118.8 ± 10.5 ms, post 121.2 ± 10.2 ms, p < 0.001) and LAS40 (Pre 38.7 ± 9.8 ms, post 40.2 ± 10.5 ms, p = 0.005) and decreased RMS40 (Pre 24.6 ± 12 ms, post 22.8 ± 12 ms, p = 0.002). LPs were present in 68/150 (45%) at baseline. Fifteen patients with negative baseline SAECGs had LPs unmasked by Procainamide, but six patients had LPs at baseline that were no longer present following Procainamide. Comparing those with normal hearts (n = 48) to those with a final diagnosis of BrS (n = 38), Procainamide prolonged fQRSd to a greater extent in those with BrS. Comparing those with Procainamide-induced LPs to those with no LPs at any time did not highlight any aspect of phenotype and did not correlate with a history of ventricular arrhythmias.
CONCLUSIONS
Procainamide influences the SAECG, provoking LPs in a small proportion of patients. However, there is no evidence that Procainamide-induced LPs provide additional diagnostic information or aid risk stratification.
Topics: Adult; Brugada Syndrome; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Voltage-Gated Sodium Channel Blockers
PubMed: 34648655
DOI: 10.1111/pace.14379 -
Journal of Visualized Experiments : JoVE Sep 2021Glycosylation is a vital modification found in proteins. N-glycan profiling of glycoproteins is required to detect novel biomarker candidates and determine glycan...
Glycosylation is a vital modification found in proteins. N-glycan profiling of glycoproteins is required to detect novel biomarker candidates and determine glycan alterations in diseases. Most commercially available biopharmaceutical proteins are glycoproteins. The efficacy of these drugs is affected by glycosylation patterns. Therefore, an in-depth characterization method for the N-glycans is necessary. Here, we present a comprehensive approach for qualitative and quantitative analysis of N-glycans using hydrophilic interaction liquid chromatography equipped with fluorescence detection and tandem mass spectrometry (HILIC-FLD-MS/MS). N-glycans were released from glycoproteins with a facile method and labeled by a procainamide fluorophore tag in the strategy. Subsequently, the procainamide labeled N-glycans were analyzed by a HILIC-FLD-MS/MS technique. In this approach, N-glycan structures were confirmed by the tandem mass spectrometric analysis, whereas fluorescence detection was used for the quantitative analysis. An application for data analysis of the detected N-glycan peaks is described in the study. This protocol can be applied to any glycoprotein extracted from various species.
Topics: Chromatography, Liquid; Glycoproteins; Hydrophobic and Hydrophilic Interactions; Polysaccharides; Tandem Mass Spectrometry
PubMed: 34633372
DOI: 10.3791/62751 -
Perfusion Mar 2023Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO)...
Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.
Topics: Adult; Humans; Procainamide; Extracorporeal Membrane Oxygenation; Acecainide; Arrhythmias, Cardiac; Tachycardia, Ventricular
PubMed: 34617854
DOI: 10.1177/02676591211050606 -
Methods in Molecular Biology (Clifton,... 2022Glycan profiling is a common strategy that is used to determine the distribution of N-linked glycans, O-linked glycans and glycolipid associated complex carbohydrate...
Glycan profiling is a common strategy that is used to determine the distribution of N-linked glycans, O-linked glycans and glycolipid associated complex carbohydrate structures that are part of various cell and tissue sources. Such data are central to our understanding of functional glycomics, and this knowledge can also be used for pathway construction and other applications in the field of Systems Glycobiology. Glycans released from cell/tissue samples are often studied in their free-form. They can also be functionalized with aglycones like 2-aminobenzamide (2AB) and procainamide to enhance separation and improve ionization during liquid chromatography/mass spectrometry. Additionally, these released glycans may be permethylated in order to improve glycan quantitation. In such work, besides studying the glycans in a single sample, there is also interest in comparing multiple samples in order to determine underlying similarities and differences, for example in terms of specific epitopes that are changed when cells of the same origin differentiate along different pathways. The current chapter describes the development and usage of cGlyco ("comparative Glycomics"), an open-source program that can be used to compare data from multiple mass spectrometry runs. As an example, we apply cGlyco to compare the glycan profile of multiple MALDI-TOF glycomics profiling data collected by core-C of the Consortium for Functional Glycomics (CFG).
Topics: Chromatography, Liquid; Glycomics; Glycoproteins; Polysaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34611866
DOI: 10.1007/978-1-0716-1685-7_5 -
International Heart Journal Sep 2021High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However,... (Observational Study)
Observational Study
High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.
Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Aortic Valve Stenosis; Atrioventricular Block; Bundle-Branch Block; Cardiac Electrophysiology; Electrocardiography; Female; Heart Valve Prosthesis; Humans; Male; Pacemaker, Artificial; Point-of-Care Testing; Predictive Value of Tests; Procainamide; Recurrence; Retrospective Studies; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34544981
DOI: 10.1536/ihj.21-145 -
Pharmaceutics Jul 2021In this study, possible changes in the expression of rat organic cationic transporters (rOCTs) and rat multidrug and toxin extrusion proteins (rMATEs) following...
Effects of 1α,25-Dihydroxyvitamin D on the Pharmacokinetics of Procainamide and Its Metabolite N-Acetylprocainamide, Organic Cation Transporter Substrates, in Rats with PBPK Modeling Approach.
In this study, possible changes in the expression of rat organic cationic transporters (rOCTs) and rat multidrug and toxin extrusion proteins (rMATEs) following treatment with 1α,25-dihydroxyvitamin D (1,25(OH)D) were investigated. Rats received intraperitoneal administrations of 1,25(OH)D for four consecutive days, and the tissues of interest were collected. The mRNA expression of rOCT1 in the kidneys was significantly increased in 1,25(OH)D-treated rats compared with the control rats, while the mRNA expressions of rOCT2 and rMATE1 in the kidneys, rOCT1 and N-acetyltransferase-II (NAT-II) in the liver, and rOCT3 in the heart were significantly decreased. Changes in the protein expression of hepatic rOCT1 and renal rOCT2 and rMATE1 were confirmed by western blot analysis. We further evaluated the pharmacokinetics of procainamide (PA) hydrochloride and its major metabolite N-acetyl procainamide (NAPA) in the presence of 1,25(OH)D. When PA hydrochloride was administered intravenously at a dose 10 mg/kg to 1,25(OH)D-treated rats, a significant decrease in renal and/or non-renal clearance of PA and NAPA was observed. A physiological model for the pharmacokinetics of PA and NAPA in rats was useful for linking changes in the transcriptional and translational expressions of rOCTs and rMATE1 transporters to the altered pharmacokinetics of the drugs.
PubMed: 34452094
DOI: 10.3390/pharmaceutics13081133 -
Advanced Emergency Nursing Journal
PubMed: 34397494
DOI: 10.1097/TME.0000000000000368 -
Advanced Emergency Nursing JournalAtrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic...
Atrial fibrillation/flutter (AF) remains the most common rhythm disturbance in adult patients presenting to emergency departments (EDs). Although pharmacologic cardioversion has been established as safe and effective in recent-onset AF, its use in U.S. EDs is uncommon. The purpose of this study was to assess the safety and efficacy of intravenous (IV) procainamide for pharmacologic cardioversion in patients presenting to the ED with AF of <48-hr duration. Patients presenting to the ED with recent-onset AF (<48 hr) undergoing a cardioversion strategy with IV procainamide from 2017 to 2019 were reviewed. Clinical outcomes assessed included rates of cardioversion, hospital admission, stroke, and return ED visits for arrhythmia or serious adverse events. A total of 64 patients received procainamide therapy-60.9% achieved cardioversion and 35.9% were admitted to the hospital. The mean dose was 1062.4 mg (12.1 mg/kg). No patients returned to the ED secondary to stroke and 9.4% experienced complications attributed to procainamide, the most common being hypotension. Within 30 days of therapy, 20.3% of patients returned to the ED secondary to arrhythmia recurrence. Patients experiencing cardioversion with procainamide were less likely to be admitted to the hospital (25.6% vs. 52.0%; p = 0.04) or receive a rate control agent (17.9% vs. 64.0%; p = 0.001). There was no significant difference in the rate of 30-day return between those who experienced pharmacologic cardioversion and those who did not (p = 0.220). The implementation of a procainamide-based acute cardioversion strategy for patients presenting to the ED with recent-onset AF resulted in a 60% cardioversion rate, which was associated with a significantly higher rate of discharge from the ED. Transient hypotension was the most common adverse event. Further investigation into ED-based protocols for management of recent-onset AF is necessary to better understand their safety and efficacy.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Procainamide; Retrospective Studies
PubMed: 34397493
DOI: 10.1097/TME.0000000000000358 -
The American Journal of Emergency... Feb 2022Flecainide is a commonly used IC antiarrhythmic. Clinical presentations of Flecainide toxicity are not commonly described.
BACKGROUND
Flecainide is a commonly used IC antiarrhythmic. Clinical presentations of Flecainide toxicity are not commonly described.
CASE REPORT
A 62 year old man on dialysis presented for evaluation of outpatient bradycardia and hypotension. In the ED, patient had wide-complex rhythm with heart rates ranging from 76 to 127. The previous day, Flecainide and Metoprolol were discontinued and patient was dialyzed and discharged. The patient was treated empirically for possible hyperkalemia. No significant change in ECG was noted with administration of calcium. Sodium bicarbonate produced questionable benefit. Potassium level was 4.6 mmol/L. Cardiac rhythm fluctuated between sinus rhythm and wide complex tachycardia in the ED & ICU. Flecainide level was 2.1 μg/ml (normal <1 μg/ml). Toxicity developed despite previous discontinuation and dialysis prior to presentation because of Flecainide's large volume of distribution and lipopholicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although Flecainide toxicity is uncommon, it has a high mortality rate, requiring early identification and treatment. Flecainide toxicity can develop in patients with hepatic or renal insufficiency, and can manifest with ventricular tachycardia or bradycardia. If suspicion of Flecainide toxicity arises, lidocaine and procainamide should be avoided to prevent further sodium channel blockade. Absence of response to calcium for a very wide complex QRS should raise clinicians' suspicion that WCT is not due to hyperkalemia, emphasizing the importance of reviewing patients' home medications. Sodium bicarbonate should be administered early to treat widened QRS. Amiodarone, intralipid emulsion therapy and ECMO may be considered in severe cases.
Topics: Anti-Arrhythmia Agents; Electrocardiography; Flecainide; Humans; Hyperkalemia; Male; Middle Aged; Tachycardia
PubMed: 34391584
DOI: 10.1016/j.ajem.2021.08.004 -
European Heart Journal. Case Reports Jun 2021Brugada syndrome (BrS) is a genetically heterogeneous channelopathy that may lead to sudden death. We report a novel mutation of the ankyrin-B gene that is probably...
BACKGROUND
Brugada syndrome (BrS) is a genetically heterogeneous channelopathy that may lead to sudden death. We report a novel mutation of the ankyrin-B gene that is probably related to the occurrence of BrS in two brothers.
CASE SUMMARY
First, we present the case of a 27-year-old male who was admitted to the hospital with acute myocarditis. The patient showed left ventricular dysfunction and was given carvedilol. Six days later, while asymptomatic and afebrile, the patient exhibited an electrocardiogram (ECG) with repolarization 'saddleback' ST changes in V2. A procainamide provocative test was performed with a response for Type 1 Brugada ECG pattern. Genetic testing revealed a novel mutation, c.5418T>A (+/-) (p.His1806Gln), in the ankyrin-B gene encoding. His 34 years old brother had an ECG J point elevation in leads V1 and V2 of 1 mm not fulfilling diagnostic criteria for Brugada ECG pattern. He also experienced arrhythmia-related syncope. Flecainide provocation test changed ECG towards a Type 1 Brugada pattern. A subcutaneous implantable defibrillator (ICD) was implanted. Patient 1 remains asymptomatic while Patient 2 experienced an appropriate ICD shock during follow-up.
DISCUSSION
In this case series, two brothers with BrS exhibited the same mutation of the ankyrin-B gene. Ankyrin-B is associated with the stability of plasma membrane proteins in the voltage-gated ion channels. Our finding provides a foundation for further investigation of this mutation in relation to BrS. Moreover, the timing of its presentation raises concerns as to whether myocarditis or beta-blockers are associated with the presentation of BrS ECG.
PubMed: 34222783
DOI: 10.1093/ehjcr/ytab225