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https://www.readbyqxmd.com/read/28912179/classification-epidemiology-and-global-burden-of-cardiomyopathies
#1
REVIEW
William J McKenna, Barry J Maron, Gaetano Thiene
In the past 25 years, major advances were achieved in the nosography of cardiomyopathies, influencing the definition and taxonomy of this important chapter of cardiovascular disease. Nearly, 50% of patients dying suddenly in childhood or adolescence or undergoing cardiac transplantation are affected by cardiomyopathies. Novel cardiomyopathies have been discovered (arrhythmogenic, restrictive, and noncompacted) and added to update the World Health Organization classification. Myocarditis has also been named inflammatory cardiomyopathy...
September 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28904293/characteristics-of-electromechanical-window-in-anesthetized-rabbit-models-of-short-qt-and-long-qt-syndromes
#2
Vudhiporn Limprasutr, Nakkawee Saengklub, Pradtana Meedech, Anusak Kijtawornrat, Robert L Hamlin
The current regulatory guidelines recommend the use of QT interval to assess the risk of arrhythmogenic potential of new chemical entities. Recently, the electromechanical window (EMW), the difference in duration between electrical and mechanical systole, has been proposed as markers for drug-induced torsades de pointes (TdP); however, data of EMW in short QT model are not available. This study aimed to characterize the EMW as a marker for drug-induced ventricular arrhythmias in anesthetized rabbit model of long QT syndrome type 2 (LQT2) and short QT syndrome (SQTS) infused with reference compounds known to lengthen or shorten QT intervals...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28827816/circadian-pattern-of-short-term-variability-of-the-qt-interval-in-primary-prevention-icd-patients-eu-cert-icd-methodological-pilot-study
#3
David J Sprenkeler, Anton E Tuinenburg, Henk J Ritsema van Eck, Marek Malik, Markus Zabel, Marc A Vos
OBJECTIVE: Short-term variability of the QT-interval (STV-QT) was shown to be associated with an increased risk of ventricular arrhythmias. We aimed at investigating (a) whether STV-QT exhibits circadian pattern, and (b) whether such pattern differs between patients with high and low arrhythmia risk. METHODS: As part of the ongoing EU-CERT-ICD study, 24h high resolution digital ambulatory 12-lead Holter recordings are collected prior to ICD implantation for primary prophylactic indication...
2017: PloS One
https://www.readbyqxmd.com/read/28827789/positional-cloning-of-quantitative-trait-nucleotides-for-blood-pressure-and-cardiac-qt-interval-by-targeted-crispr-cas9-editing-of-a-novel-long-non-coding-rna
#4
Xi Cheng, Harshal Waghulde, Blair Mell, Eric E Morgan, Shondra M Pruett-Miller, Bina Joe
Multiple GWAS studies have reported strong association of cardiac QT-interval to a region on HSA17. Interestingly, a rat locus homologous to this region is also linked to QT-intervals. The high resolution positional mapping study located the rat QT-interval locus to a <42.5kb region on RNO10. This region contained no variants in protein-coding sequences, but a prominent contiguous 19bp indel polymorphism was noted within a novel predicted long non-coding RNA (lncRNA), which we named as Rffl-lnc1. To assess the candidacy of this novel lncRNA on QT-interval, targeted CRISPR/Cas9 based genome-engineering approaches were applied on the rat strains used to map this locus...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28814790/in-silico-investigation-of-a-kcnq1-mutation-associated-with-short-qt-syndrome
#5
Ismail Adeniran, Dominic G Whittaker, Aziza El Harchi, Jules C Hancox, Henggui Zhang
Short QT syndrome (SQTS) is a rare condition characterized by abnormally 'short' QT intervals on the ECG and increased susceptibility to cardiac arrhythmias and sudden death. This simulation study investigated arrhythmia dynamics in multi-scale human ventricle models associated with the SQT2-related V307L KCNQ1 'gain-of-function' mutation, which increases slow-delayed rectifier potassium current (IKs). A Markov chain (MC) model recapitulating wild type (WT) and V307L mutant IKs kinetics was incorporated into a model of the human ventricular action potential (AP) for investigation of QT interval changes and arrhythmia substrates...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812984/modelling-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-3-in-the-human-ventricles
#6
Cunjin Luo, Kuanquan Wang, Henggui Zhang
Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current IK1) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3...
August 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28759457/genetic-causes-of-sudden-cardiac-death-in-children-inherited-arrhythmogenic-diseases
#7
Gaetano Vacanti, Riccardo Maragna, Silvia G Priori, Andrea Mazzanti
PURPOSE OF REVIEW: In this chapter we will discuss the most recent and relevant evidences published in the field of inherited arrhythmogenic disorders, focusing on the so called 'channelopathies' that are associated with sudden cardiac death (SCD) in children: long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). RECENT FINDINGS: We will discuss the latest diagnostic criteria for channelopathies released by the European Society of Cardiology, the new data on BrS in children and the recent evidence supporting a genotype-specific therapy for LQTS type 3...
October 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28711067/pa-6-inhibits-inward-rectifier-currents-carried-by-v93i-and-d172n-gain-of-function-kir2-1-channels-but-increases-channel-protein-expression
#8
Yuan Ji, Marlieke G Veldhuis, Jantien Zandvoort, Fee L Romunde, Marien J C Houtman, Karen Duran, Gijs van Haaften, Eva-Maria Zangerl-Plessl, Hiroki Takanari, Anna Stary-Weinzinger, Marcel A G van der Heyden
BACKGROUND: The inward rectifier potassium current IK1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased IK1, short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC50 = 14 nM with inside-out patch clamp methodology) and specific IK1 inhibitor that interacts with the cytoplasmic pore region of the KIR2...
July 15, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28685701/the-role-of-quinidine-in-the-pharmacological-therapy-of-ventricular-arrhythmias-quinidine
#9
Bojana Bozic, Teodora Vidonja Uzelac, Aleksandra Kezic, Milica Bajcetic
BACKGROUND: Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation...
July 7, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28660286/hydrocinnamic-acid-inhibits-the-currents-of-wt-and-sqt3-syndrome-related-mutants-of-kir2-1-channel
#10
Shuxi Ren, Chunli Pang, Yayue Huang, Chengfen Xing, Yong Zhan, Hailong An
Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.1. Here, we determined a monomer, hydrocinnamic acid (HA), as the effective component from 18 compounds of styrax. Our data show that HA can inhibit the currents of Kir2.1 channel in both excised inside-out and whole-cell patch with the IC50 of 5.21 ± 1.02 and 10.08 ± 0.46 mM, respectively...
June 28, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28659867/increased-short-term-beat-to-beat-qt-interval-variability-in-patients-with-impaired-glucose-tolerance
#11
Andrea Orosz, István Baczkó, Szabolcs Nyiraty, Anna E Körei, Zsuzsanna Putz, Róbert Takács, Attila Nemes, Tamás T Várkonyi, László Balogh, György Ábrahám, Péter Kempler, Julius Gy Papp, András Varró, Csaba Lengyel
Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 ± 11 years, body mass index (BMI): 31 ± 6 kg/m(2), fasting glucose: 6.0 ± 0.4 mmol/l, 120 min postload glucose: 9.0 ± 1.0 mmol/l, hemoglobin A1c (HbA1c): 5...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28640933/could-ivabradine-be-a-new-treatment-for-the-short-qt-syndrome
#12
EDITORIAL
Jules C Hancox
No abstract text is available yet for this article.
September 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28632743/in-silico-assessment-of-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-1-in-the-human-ventricles
#13
Cunjin Luo, Kuanquan Wang, Henggui Zhang
AIMS: Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1...
2017: PloS One
https://www.readbyqxmd.com/read/28617967/holter-monitored-sudden-cardiac-arrest-after-atrioventricular-junction-ablation
#14
Victor Waldmann, Eloi Marijon, Nicolas Combes
We present a case of sudden cardiac arrest 7 hours after radiofrequency ablation of the atrioventricular junction for symptomatic permanent atrial fibrillation unresponsive to medical therapy. The Holter monitoring revealed a progressive increasing of QT interval after the procedure, highlighting the repolarization instability after acute changes in heart rates associated with modification of ventricular activation, leading to occurrence of short coupling interval ventricular extra beats and finally to a "torsade de pointes...
June 15, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28611676/autonomic-modulation-in-patients-with-heart-failure-increases-beat-to-beat-variability-of-ventricular-action-potential-duration
#15
Bradley Porter, Martin J Bishop, Simon Claridge, Jonathan Behar, Benjamin J Sieniewicz, Jessica Webb, Justin Gould, Mark O'Neill, Christopher A Rinaldi, Reza Razavi, Jaswinder S Gill, Peter Taggart
Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined. Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation-recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28609477/atrial-arrhythmogenicity-of-kcnj2-mutations-in-short-qt-syndrome-insights-from-virtual-human-atria
#16
Dominic G Whittaker, Haibo Ni, Aziza El Harchi, Jules C Hancox, Henggui Zhang
Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28592292/effects-of-amiodarone-on-short-qt-syndrome-variant-3-in-human-ventricles-a-simulation-study
#17
Cunjin Luo, Kuanquan Wang, Henggui Zhang
BACKGROUND: Short QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS...
June 7, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28584788/clinical-implications-of-new-drugs-and-regimens-for-the-treatment-of-drug-resistant-tuberculosis
#18
REVIEW
Yong-Soo Kwon
The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB...
May 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28574954/short-term-variability-of-repolarization-is-superior-to-other-repolarization-parameters-in-the-evaluation-of-diverse-antiarrhythmic-interventions-in-the-chronic-atrioventricular-block-dog
#19
Alexandre Bossu, Rosanne Varkevisser, Henriette D M Beekman, Marien J C Houtman, Marcel A G van der Heyden, Marc A Vos
Short-term variability (STV), to quantify beat-to-beat variability of repolarization, is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed but also in vulnerable patients with heart failure or drug-induced long QT syndrome. In the CAVB dog model, STV can specifically distinguish between safe and unsafe drugs in proarrhythmic screening. Conversely, this dog model also offers the possibility to evaluate antiarrhythmic strategies in a setting of Torsades de Pointes (TdP) induction with a standard IKr inhibitor...
June 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28569435/the-new-kids-on-the-block-of-arrhythmogenic-disorders-short-qt-syndrome-and-early-repolarization
#20
REVIEW
Andrea Mazzanti, Katherine Underwood, Dmitriy Nevelev, Shanna Kofman, Silvia G Priori
Short QT syndrome (SQTS) is one of the rarest inheritable cardiac channelopathies, characterized by an accelerated cardiac repolarization, which is also the substrate for the development of life-threatening ventricular arrhythmias. Up to this date, fewer than 200 SQTS cases have been reported in the literature worldwide. Patients with SQTS may experience a cardiac arrest as early as in the neonatal period or as late as 80 years old. The cumulative probability of experiencing a cardiac arrest by the fifth decade of life approaches 40%, highlighting the importance of early recognition and management...
June 1, 2017: Journal of Cardiovascular Electrophysiology
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