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Annals of Pediatric Cardiology 2021Junctional ectopic tachycardia (JET) is more common in its postoperative form. A thorough understanding of its etiology, pathophysiology, and management strategies is... (Review)
Review
Junctional ectopic tachycardia (JET) is more common in its postoperative form. A thorough understanding of its etiology, pathophysiology, and management strategies is essential. Classically, postoperative JET is considered to arise from surgical trauma. Genetic susceptibility and an intrinsic morphologic/functional defect in the conduction system inherent in congenital heart diseases likely play a significant role. The devastating effects on postoperative hemodynamics warrant prompt attention. A multipronged management approach with general measures, pharmacotherapy, and pacing has decreased morbidity and mortality. Amiodarone and procainamide remain the preferred drugs, while ivabradine appears promising. Carefully planned randomized trials can go a long way in developing a systematic management protocol for postoperative JET.
PubMed: 34667411
DOI: 10.4103/apc.apc_35_21 -
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 -
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 -
Journal of Medicinal Chemistry Jul 2021Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized...
Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized suberoylanilide hydroxamic acid (SAHA) derivatives that chemically combine the pan-histone deacetylase inhibitor SAHA with the DNA methyltransferase inhibitor procainamide. A three- or four-step chemical synthesis was designed starting from cheap raw materials. Compared to the single drugs, the combined molecules showed a superior activity in and a potent inhibition against human HDAC6, exerting no cytotoxicity in human cell lines. These new compounds are fully active in multidrug-resistant Cambodian isolates. They target transmission of the parasite by inducing irreversible morphological changes in gametocytes and inhibiting exflagellation. The compounds are slow-acting and have an additive antimalarial effect in combination with fast-acting epidrugs and dihydroartemisinin. The lead compound decreases parasitemia in mice in a severe malaria model. Taken together, this novel fused molecule offers an affordable alternative to current failing antimalarial therapy.
Topics: Antimalarials; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Hydroxamic Acids; Malaria, Falciparum; Molecular Structure; Plasmodium falciparum; Procainamide; Structure-Activity Relationship
PubMed: 34185525
DOI: 10.1021/acs.jmedchem.1c00821 -
Journal of Alzheimer's Disease : JAD 2021Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with...
Safety of Memantine in Combination with Potentially Interactive Drugs in the Real World: A Pharmacovigilance Study Using the Japanese Adverse Drug Event Report (JADER) Database.
BACKGROUND
Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with some specific drugs such as amantadine or dextromethorphan due to potential interactions that might augment the adverse effects of memantine.
OBJECTIVE
This notification has not been validated in real-world data, which we aim to address using a large self-reporting database from Japan.
METHODS
We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database reported between April 2004 and March 2019 for detecting the neuropsychiatric adverse event (AE) signals associated with memantine and other potentially interactive drugs including amantadine, dextromethorphan, cimetidine, ranitidine, procainamide, quinidine, acetazolamide, citrate, and bicarbonate. Drug-drug interactions between memantine and these drugs were assessed using multiplicative and additive models.
RESULTS
There was no statistically robust evidence to support multiplicative or additive interactions between memantine and the aforementioned drugs to increase the reporting of any included neuropsychiatric AEs or AE categories.
CONCLUSION
The real-world JADER data did not raise the concern about the interactive increase in the neuropsychiatric AEs in patients with dementia taking memantine in combination with amantadine or dextromethorphan, suggesting there may be no urgent need to prohibit the co-administration of these drugs presently.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Alzheimer Disease; Databases, Factual; Drug Interactions; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Excitatory Amino Acid Antagonists; Female; Humans; Japan; Male; Memantine; Pharmacovigilance; Retrospective Studies
PubMed: 34151816
DOI: 10.3233/JAD-210524 -
Cureus Apr 2021Myocardial ischemia may lead to lethal arrhythmias. Treatment of these arrhythmias without addressing the cause of ischemia may be futile. The length of resuscitation is...
BACKGROUND
Myocardial ischemia may lead to lethal arrhythmias. Treatment of these arrhythmias without addressing the cause of ischemia may be futile. The length of resuscitation is an important parameter for determining when to stop resuscitation but with shockable rhythms and reversible cause of the cardiac arrest, the decision to terminate resuscitation is complex. Case Summary: A patient with a three-month history of shortness of breath with effort developed pulseless ventricular tachycardia (VT) at the early stages of a stress test. In coronary angiography, a critical lesion in the right coronary artery (RCA) was observed and treated with two stents. During the procedure and for a total of five hours, the patient had more than 100 separate episodes of VT and ventricular fibrillation (VF) that were treated by 150 defibrillations, artificial ventilation, intra-aortic counter-pulsation balloon insertion, and multiple drugs. One hour after the initial stenting procedure, thrombosis of the RCA was demonstrated and treated successfully with angioplasty. Use of procainamide resolved the arrhythmias and the patient recovered completely without neurological deficit, ejection fraction of 45%, and is asymptomatic at one year following the event.
DISCUSSION
Our case shows that with a revisable cause of cardiac arrest, resuscitation should be directed at maintaining perfusion of essential organs and treating the reversible cause. Without re-opening the RCA, we could not have saved the patient's life. The use of an extracorporeal membrane oxygenator, if available, should be considered in similar cases. Finally, the quality of cardiopulmonary resuscitation determines the neurological outcome regardless of the length of resuscitation, as was evident in our patient who recovered completely.
PubMed: 33954068
DOI: 10.7759/cureus.14255 -
Diagnostics (Basel, Switzerland) Feb 2021In the last few years, cardiac magnetic resonance (CMR) imaging has progressively acquired a central role in the diagnosis and management of patients with ventricular...
In the last few years, cardiac magnetic resonance (CMR) imaging has progressively acquired a central role in the diagnosis and management of patients with ventricular arrhythmias (VA) [...].
PubMed: 33672729
DOI: 10.3390/diagnostics11020357 -
PLoS Neglected Tropical Diseases Feb 2021African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional...
African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naïve tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type N-glycans. In overlay assays, these sugars were differentially recognized by the mannose receptor and DC-SIGN C-type lectins. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host.
Topics: Animals; Chromatography, Liquid; Concanavalin A; Glycoproteins; Glycoside Hydrolases; Insect Vectors; Lectins, C-Type; Polysaccharides; Saliva; Salivary Glands; Salivary Proteins and Peptides; Tandem Mass Spectrometry; Trypanosoma; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 33529215
DOI: 10.1371/journal.pntd.0009071 -
Diagnostics (Basel, Switzerland) Jan 2021Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy...
Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients (age 53.0 [42.0-58.0]; 52% female, left ventricular ejection fraction 55 ± 9%) were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced (mean change systolic BP -12 ± 9 mmHg; diastolic BP -4 ± 9 mmHg), while the baseline heart rate (HR) remained relatively unchanged (mean HR change -1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function.
PubMed: 33513676
DOI: 10.3390/diagnostics11020178