- Retrieving hidden atrial repolarization waves from standard surface ECGs. [Journal Article]
- BEBiomed Eng Online 2018 Nov 06; 17(Suppl 2):146
- CONCLUSIONS: This extraction makes many diseases, such as acute atrial infarction or arrhythmia, become easily diagnosed.
- Prevalence and risk factors of acquired long QT syndrome in hospitalized patients with chronic kidney disease. [Journal Article]
- JIJ Investig Med 2018 Oct 26
- Patients with chronic kidney disease (CKD) have a high risk of fatal arrhythmias. The extended severe corrected QT (QTc) interval is a hallmark of ventricular arrhythmias and sudden cardiac death. Th...
Patients with chronic kidney disease (CKD) have a high risk of fatal arrhythmias. The extended severe corrected QT (QTc) interval is a hallmark of ventricular arrhythmias and sudden cardiac death. The objective of this study was to evaluate the prevalence of acquired long QT syndrome (aLQTS) in hospitalized patients with CKD and search for potential risk factors to improve clinical risk stratification in patients with CKD. Information about patients with CKD was retrospectively collected in our hospital between January 2013 and June 2017. The prevalence of aLQTS in different stages of CKD was evaluated. The common risk factors for QTc prolongation in patients with CKD were compiled, and multivariable logistic regression analysis was used to evaluate how each factor was related to aLQTS in CKD. A total of 804 patients with CKD (299 females, 37.2%) participated in our study. The prevalence of aLQTS among all 804 patients was 56.97%, and the prevalence of QTc prolongation (>500 ms) was 10.07%. Among the elderly, impaired kidney function, hemodialysis, low serum potassium and low left ventricular ejection fraction (LVEF) were associated with QTc prolongation in patients with CKD. The prevalence of aLQTS is much higher and increases with the decline of kidney function in hospitalized patients with CKD, which is related to older age, impaired kidney function, hemodialysis, serum potassium and low LVEF.
- Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy. [Journal Article]
- MGMol Genet Genomic Med 2018 Oct 21
- CONCLUSIONS: These estimates of penetrance and expressivity, for this specific variant, may be useful in clinical practice. Review of the literature indicates that individual CACNA1C variants have their own particular genotype-phenotype correlations. We suggest that, at least in respect of the particular variant reported here, "arrhythmogenic channelopathy" may be a more fitting nomenclature than long QT syndrome.
- Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration. [Journal Article]
- AAAntimicrob Agents Chemother 2018; 62(12)
- Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisin...
Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisinin-piperaquine (DHA-PQP) appears to be suitable as a candidate for MDA. However, the absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA. We conducted an interventional study in Lihir Island, Papua New Guinea, using healthy individuals age 3 to 60 years who received a standard 3-day course of DHA-PQP on 3 consecutive months. Twelve-lead electrocardiography (ECG) readings were conducted predose and 4 h after the final dose of each month. The primary safety endpoint was QT interval correction (QTc using Fridericia's correction [QTcF]) prolongation from baseline to 4 h postdosing. We compared the difference in prolongations between the third course postdose and the first course postdose. Of 84 enrolled participants, 69 (82%) participants completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (standard deviation [SD], 17.8 ms) and 17.1 ms (SD, 17.1 ms) for the first-course and third-course postdosing ECGs risk difference, -2.4 (95% confidence interval [95% CI], -6.9 to 2.1; P = 0.285), respectively. We recorded a QTcF prolongation of >60 ms from baseline in 3 (4.3%) and 2 (2.9%) participants after the first course and third course (P = 1.00), respectively. No participants had QTcF intervals of >500 ms at any time point. Three consecutive monthly courses of DHA-PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing supports the use of monthly DHA-PQP as part of malaria elimination strategies.
- Seizure-like episodes and EEG abnormalities in patients with long QT syndrome. [Journal Article]
- SSeizure 2018; 61:214-220
- CONCLUSIONS: Seizure-like episodes and EEG abnormalities were common in our cohort with cLQTS patients. However, we could not find firm evidence of epilepsy. Our findings reinforce the notion that cLQTS is a cardiocerebral channelopathy. Correct classification of seizures may be challenging to the clinician, but of vital importance for patients.
- Multiple serial ECGs aid with the diagnosis and prognosis of Brugada syndrome. [Journal Article]
- IJInt J Cardiol 2018 Aug 30
- CONCLUSIONS: Our study illustrates the need for multiple ECGs to aid with both the diagnosis and prognosis of BrS. Serial ECGs can assist with risk stratification based on the fraction of ECGs that display a spontaneous Type-I BrS ECG.
- Moxifloxacin-induced QT interval prolongation and torsades de pointes: a narrative review. [Review]
- EOExpert Opin Drug Saf 2018; 17(10):1029-1039
- Moxifloxacin is widely used for the treatment of a number of infectious diseases because of its favorable pharmacological profile and high clinical success rate. However, it is often criticized for i...
Moxifloxacin is widely used for the treatment of a number of infectious diseases because of its favorable pharmacological profile and high clinical success rate. However, it is often criticized for its higher risk of QTc interval prolongation (QTIP) and torsades de pointes (TdP). Areas covered: A review of published literature on moxifloxacin-related QTIP and TdP. Readers will be provided with a comprehensive overview of the prevalence, cellular mechanism, risk factors, and magnitude of QTIP of moxifloxacin. Expert commentary: In healthy subjects, moxifloxacin prolongs the QTc interval by 11.5-19.5 ms, it binds at the Tyr652 residue in the S6 pore domain of the human ether a-go-go gene related potassium channel. Considerable QTIP (30-60 ms) have also been reported in some patients, for instance the incidence of QTIP (30-60 ms) in elderly pneumonia patients was 15.5%. Moxifloxacin-induced QTIP may be of little clinical importance in healthy individuals. However, marked QTIP (>60 ms) and TdP have been reported in high-risk patients (patients who have multiple QT prolonging risk factors). Patients must be thoroughly assessed prior to the use of moxifloxacin and high-risk patients must be identified using risk assessment tools to ensure safe use of moxifloxacin and to safeguard patients' health.
- Utility of the JT Peak Interval and the JT Area in Determining the Proarrhythmic Potential of QT-Shortening Agents. [Journal Article]
- JCJ Cardiovasc Pharmacol Ther 2018 Aug 09; :1074248418791999
- Drug-induced long QT increases the risk of ventricular tachyarrhythmia known as torsades de pointes (TdP). Many biomarkers have been used to predict TdP. At present, however, there are few biomarkers...
Drug-induced long QT increases the risk of ventricular tachyarrhythmia known as torsades de pointes (TdP). Many biomarkers have been used to predict TdP. At present, however, there are few biomarkers for arrhythmias induced by QT-shortening drugs. The objective of the present study was to identify the best biomarkers for predicting arrhythmias caused by the 4 potassium channel openers ICA-105574, NS-1643, R-L3, and pinacidil. Our results showed that, at higher concentrations, all 4 potassium channel openers induced ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts, but not in rabbit hearts. The electrocardiography parameters were measured including QT/QTc, JT peak, Tp-e interval, JT area, short-term beat-to-beat QT interval variability (STV), and index of cardiac electrophysiological balance (iCEB). We found that the potassium channel openers at test concentrations shortened the QT/QTc and the JT peak interval and increased the JT area. Nevertheless, even at proarrhythmic concentrations, they did not always change STV, Tp-e, or iCEB. Receiver operating characteristic curve analysis showed that the JT peak interval representing the early repolarization phase and the JT area reflecting the dispersion of ventricular repolarization were the best predictors of VT/VF. Action potential recordings in guinea pig papillary muscle revealed that except for pinacidil, the potassium channel openers shortened APD30 in a concentration-dependent manner. They also evoked early or delayed afterdepolarizations at fast pacing rates. Patch-clamp recordings in guinea pig ventricular cardiomyocytes showed that the potassium channel openers enhanced the total outward currents during the early phase of action potential repolarization, especially at proarrhythmic concentrations. We concluded that the JT peak interval and the JT area are surrogate biomarkers identifying the risk of proarrhythmia associated with the administration of QT-shortening agents. The acceleration of early-phase repolarization and the increased dispersion of ventricular repolarization may contribute to the occurrence of arrhythmias.
- Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography. [Journal Article]
- HVHeart Vessels 2018 Jul 25
- Heterologous expression systems play a vital role in the characterization of potassium voltage-gated channel subfamily H member 2 (KCNH2) gene mutations, such as E637K which is associated with long Q...
Heterologous expression systems play a vital role in the characterization of potassium voltage-gated channel subfamily H member 2 (KCNH2) gene mutations, such as E637K which is associated with long QT syndrome type 2 (LQT2). In vivo assays using zebrafish provide a means for testing genetic variants of cardiac disease; however, limited information on the role of the E637K mutation is available from in vivo systems and their utility has yet to be fully exploited in the context of LQT2. We sought to evaluate the ability of the E637K mutant channel to restore normal repolarization in larval zebrafish with a human KCNH2 orthologue, kcnh2a-knockdown. A morpholino (MO) targeting kcnh2a was injected alone or with wild type (WT) or E637K KCNH2 cRNA into zebrafish embryos at the 1-2 cell stage. Cardiac repolarization phenotypes were screened using light microscopy and the QT interval was measured by single lead electrocardiograph (ECG) analysis at 72-h post-fertilization. In the MO alone group, 17% of zebrafish had a normal phenotype; this rate increased to 60% in the WT KCNH2 cRNA injected zebrafish and to 35% in the E637K injected zebrafish. The ECG of larval zebrafish revealed that QTc was significantly prolonged in the MO alone group compared to the control group. Co-injection of WT KCNH2 cRNA shortened the QTc interval, however, that of the E637K did not. We suggest that this in vivo cardiac assay using microscopy and ECG in larval zebrafish offers a reliable approach for risk discrimination of KCNH2 mutations.
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- QT instability, an indicator of augmented arrhythmogenesis, increases with the progression of myxomatous mitral valve disease in dogs. [Journal Article]
- JVJ Vet Cardiol 2018; 20(4):254-266
- CONCLUSIONS: Analyses of QT intervals demonstrated changes in STI, LTI, and TI. Increased QT prolongation and instability are significantly related to mortality and may be useful in determining prognosis of MMVD patients.