Effects of acute alcohol consumption on cardiac excitation, conduction, and repolarization: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW).
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SUBMITTER: Brunner S
PROVIDER: S-EPMC8166672 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Effects of acute alcohol consumption on cardiac excitation, conduction, and repolarization: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW).
Brunner Stefan S Drobesch Cathrine C Herbel Rebecca R Sinner Moritz F MF
Clinical research in cardiology : official journal of the German Cardiac Society 20210318 6
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Project description:AimsAlcohol is a risk factor for cardiac arrhythmias. Retrospective analyses suggest supraventricular arrhythmias consecutive to acute alcohol consumption, but prospective data are limited. We intended to prospectively associate acute alcohol consumption with cardiac arrhythmias.Methods and resultsAt the 2015 Munich Octoberfest, we enrolled 3028 voluntary participants who received a smartphone-based ECG and breath alcohol concentration (BAC) measurements. ECGs were analysed for cardiac arrhythmias (sinus tachycardia, sinus arrhythmia, premature atrial/ventricular complexes, atrial fibrillation/flutter) and respiratory sinus arrhythmia. By multivariable adjusted logistic regression we associated BACs with cardiac arrhythmias. Similarly, we analysed 4131 participants of the community-based KORA S4 Study (Co-operative Health Research in the Region of Augsburg) and associated cardiac arrhythmias with chronic alcohol consumption. In our acute alcohol cohort (mean age 34.4 ± 13.3 years, 29% women), mean BAC was 0.85 ± 0.54 g/kg. Cardiac arrhythmias occurred in 30.5% (sinus tachycardia 25.9%; other arrhythmia subtypes 5.4%). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall (odds ratio (OR) per 1-unit change 1.75, 95% confidence interval (CI) 1.50-2.05; P < 0.001) and sinus tachycardia in particular (OR 1.96, 95%CI 1.66-2.31; P < 0.001). Respiratory sinus arrhythmia measuring autonomic tone was significantly reduced under the influence of alcohol. In KORA S4, chronic alcohol consumption was associated with sinus tachycardia (OR 1.03, 95%CI 1.01-1.06; P = 0.006).ConclusionsAcute alcohol consumption is associated with cardiac arrhythmias and sinus tachycardia in particular. This partly reflects autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday heart syndrome.Clinicaltrials.org accession numberNCT02550340.
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Project description:BackgroundThere is increasing evidence that the effects of Huntington's disease (HD) extend beyond the central nervous system. In particular, significant cardiac dysfunction has been described in transgenic mouse models and suggested in symptomatic patients, in whom cardiac involvement could provide an independent risk for sudden cardiac death.MethodsStandard 12-lead electrocardiograms (ECGs) obtained at screening from 590 early symptomatic (Stage 1 and 2) HD patients participating in a multi-site Phase III study were analyzed.ResultsEvaluating only those ECGs in individuals not on medications or with potentially contributing medical conditions, the prevalence of bradycardia was 28.3% (marked in 5.8%), prolonged QRS 4.9%, intraventricular conduction delay 3.4%, right bundle branch block 1.3%, and QTc prolongation 3.7%.ConclusionSignificant cardiac abnormalities, characterized primarily by conduction abnormalities, were found in a larger than expected number of patients. Abnormal intraventricular conduction may lead to increased risk for arrhythmia and may be compounded by prescription of QT-prolonging medications.
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Project description:PurposeMidostaurin (PKC412) is a multitargeted tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 receptor (FLT3), c-KIT, and other receptors. Midostaurin is active in patients with acute myeloid leukemia and systemic mastocytosis. Although no substantive risk for cardiac abnormalities has been observed with midostaurin in clinical studies thus far, some TKIs have been shown to affect cardiac repolarization. Here we evaluated midostaurin's effect on cardiac repolarization.MethodsThis phase I study evaluated the effect of midostaurin (75 mg twice daily for 2 days; 75 mg once on day 3) on the heart rate-corrected QT (QTc) interval in a parallel design with active (moxifloxacin) and placebo control arms in healthy volunteers.ResultsThe maximum mean QTc change from baseline corrected using Fridericia's correction (QTcF) for midostaurin compared with placebo was 0.7 ms at 24 h post dose on day 3. The highest upper bound of the 1-sided 95% CI was 4.7 ms, which excluded 10 ms, demonstrating a lack of QTcF prolongation effect. Assay sensitivity was demonstrated by modeling the moxifloxacin plasma concentration versus QTcF change from baseline, which showed a clear positive increase in QTcF with increasing moxifloxacin plasma concentrations, as expected based on previous studies. In the 4-day evaluation period, a minority of participants (34.6%) experienced an adverse event; 97.0% were grade 1. No grade 3 or 4 adverse events were reported.ConclusionMidostaurin demonstrated a good safety profile in healthy volunteers, with no prolonged cardiac repolarization or other changes on the electrocardiogram.
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Project description:BackgroundDisorders affecting cardiac conduction are associated with substantial morbidity. Understanding the epidemiology and risk factors for conduction disorders may enable earlier diagnosis and preventive efforts.ObjectivesThe purpose of this study was to quantify contemporary frequency and risk factors for electrocardiogram (ECG)-defined cardiac conduction disorders in a large multi-institutional primary care sample.MethodsWe quantified prevalence and incidence of conduction disorders among adults receiving longitudinal primary care between 2001 and 2019, each with at least one 12-lead ECG performed prior to the start of follow-up and at least one ECG during follow-up. We defined conduction disorders using curated terms extracted from ECG diagnostic statements by cardiologists. We grouped conduction disorders by inferred anatomic location of abnormal conduction. We tested associations between clinical factors and incident conduction disease using multivariable proportional hazards regression.ResultsWe analyzed 189,163 individuals (median age 55 years; 58% female). The overall prevalence of conduction disorders was 27% among men and 15% among women. Among 119,926 individuals (median age 55 years; 51% female), 6,802 developed an incident conduction system abnormality over a median of 10 years (Q1, Q3: 6, 15 years) of follow-up. Incident conduction disorders were more common in men (8.78 events/1,000 person-years) vs women (4.34 events/1,000 person-years, P < 0.05). In multivariable models, clinical factors including older age (HR: 1.25 per 5-year increase [95% CI: 1.24-1.26]) and myocardial infarction (HR: 1.39 [95% CI: 1.26-1.54]) were associated with incident conduction disorders.ConclusionsCardiac conduction disorders are common in a primary care population, especially among older individuals with cardiovascular risk factors.
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Project description:BackgroundThe study aims to analyse the action of zingerone in diabetes-related cardiac arrhythmias.MethodsDiabetes was induced by streptozocin while treatment groups received 20 mg/kg zingerone daily. Following extra seven weeks, electrocardiography, extraction of blood, urine and heart for biochemical analysis, histopathology and immunofluorescence were undertaken.ResultsThe suppression of QT and QTc prolongation in diabetic rats was indicative of prolonged cardiac repolarisation that was greatly reduced by zingerone treatment. In addition, the reduction in PR interval attested that zingerone improved AV delay in diabetic rats. The fibrogenic transforming growth factor β1 upregulation in diabetic hearts was suppressed by zingerone. The marked glycogen deposition and muscle degeneration seen in diabetic heart sections were also alleviated by zingerone. Furthermore, zingerone prevented the decrease in of the serum anti-inflammatory cytokine adiponectin in diabetics. The heightened levels of oxidative stress markers 8-isoprostane and uric acid in diabetic rats were suppressed. In the diabetic heart, the reduced catalase activity was improved and the excessive expression of angiotensin receptor 1 was inhibited by zingerone.ConclusionCardiac delayed repolarisation and AV conduction in rats with diabetes were halted by zingerone. It appears that inhibition of cardiac fibrosis and associated inflammation-oxidative stress signalling underpins the zingerone effect.
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Project description:AimsCladribine tablets have shown significant efficacy for the treatment of relapsing multiple sclerosis, a chronic and debilitating immune-mediated disorder. This study was conducted to examine acute and/or cumulative effects of cladribine tablets 10 mg (3.5 or 5.25 mg/kg cumulative dose over 2 years) on heart rate, AV conduction and cardiac repolarization in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsCLARITY was a 96-week, double-blind, placebo-controlled, multicentre trial which evaluated the safety and efficacy of cladribine tablets 3.5 and 5.25 mg/kg body weight in patients with RRMS. A total of 135 patients were included in the ECG substudy, providing a total of 1534 post-dose ECGs. ECG data were collected 15 minutes pre-dose and between 0.5 and 3 hours post-dose at pre-study evaluation, study Day 1 and Weeks 5, 9, 13, 48 and 52.ResultsFor cladribine tablets 3.5 mg/kg, the maximum change in placebo-adjusted post-dose QTcF vs. visit-baseline (BL) was -0.42 ms (90% CI: -3.61-4.44) at Week 1 (acute effects), and 3.20 ms (90% CI: -0.08-6.33) for cladribine tablets 5.25 mg/kg. The greatest observed differences in post-dose QTcF vs. study BL occurred at Week 48 for both the 3.5 and 5.25 mg/kg doses of cladribine tablets with 5.99 ms (90% CI: 0.53-11.44) and 8.74 ms (90% CI: 3.18-14.31), respectively. No significant changes were observed in T-wave morphology in either treatment group.ConclusionsCladribine tablets 3.5 mg/kg (approved dose in Europe/other regions) did not confer clinically meaningful effects on heart rate, AV conduction and ventricular repolarization.
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Project description:A moderate alcohol consumption is demonstrated to exert a protective action in terms of cardiovascular risk. Although this property seems not to be beverage-specific, the various composition of alcoholic compounds could mediate peculiar effects in vivo. The aim of this study was to evaluate potential beer-mediated effects on the cardiovascular health in humans, using a meta-analytic approach (trial registration number: CRD42018118387). The literature search, comprising all English articles published until November, 30th 2019 in EMBASE, PubMed and Cochrane database included all controlled clinical trials evaluating the cardiovascular effects of beer assumption compared to alcohol-free beer, water, abstinence or placebo. Both sexes and all beer preparations were considered eligible. Outcome parameters were those entering in the cardiovascular risk charts and those related to endothelial dysfunction. Twenty-six trials were included in the analysis. Total cholesterol was significantly higher in beer drinkers compared to controls (14 studies, 3.52 mg/dL, 1.71-5.32 mg/dL). Similar increased levels were observed in high-density lipoprotein (HDL) cholesterol (18 studies, 3.63 mg/dL, 2.00-5.26 mg/dL) and in apolipoprotein A1 (5 studies, 0.16 mg/dL, 0.11-0.21 mg/dL), while no differences were detected in low density lipoprotein (LDL) cholesterol (12 studies, -2.85 mg/dL, -5.96-0.26 mg/dL) and triglycerides (14 studies, 0.40 mg/dL, -5.00-5.80 mg/dL) levels. Flow mediated dilation (FMD) resulted significantly higher in beer-consumers compared to controls (4 studies, 0.65%, 0.07-1.23%), while blood pressure and other biochemical markers of inflammation did not differ. In conclusion, the specific beer effect on human cardiovascular health was meta-analysed for the first time, highlighting an improvement of the vascular elasticity, detected by the increase of FMD (after acute intake), and of the lipid profile with a significant increase of HDL and apolipoprotein A1 serum levels. Although the long-term effects of beer consumption are not still understood, a beneficial effect of beer on endothelial function should be supposed.
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Project description:Spatially discordant alternans (SDA) of action potential duration (APD) has been widely observed in cardiac tissue and is linked to cardiac arrhythmogenesis. Theoretical studies have shown that conduction velocity restitution (CVR) is required for the formation of SDA. However, this theory is not completely supported by experiments, indicating that other mechanisms may exist. In this study, we carried out computer simulations using mathematical models of action potentials to investigate the mechanisms of SDA in cardiac tissue. We show that when CVR is present and engaged, such as fast pacing from one side of the tissue, the spatial pattern of APD in the tissue undergoes either spatially concordant alternans or SDA, independent of initial conditions or tissue heterogeneities. When CVR is not engaged, such as simultaneous pacing of the whole tissue or under normal/slow heart rates, the spatial pattern of APD in the tissue can have multiple solutions, including spatially concordant alternans and different SDA patterns, depending on heterogeneous initial conditions or pre-existing repolarization heterogeneities. In homogeneous tissue, curved nodal lines are not stable, which either evolve into straight lines or disappear. However, in heterogeneous itssue, curved nodal lines can be stable, depending on their initial locations and shapes relative to the structure of the heterogeneity. Therefore, CVR-induced SDA and non-CVR-induced SDA exhibit different dynamical properties, which may be responsible for the different SDA properties observed in experimental studies and arrhythmogenesis in different clinical settings.
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2025-05-06 | PXD051011 | Pride
Project description:BackgroundThe role of IKs, the slow delayed rectifier K+ current, in cardiac ventricular repolarization has been a subject of debate.Methods and resultsWe develop a detailed Markov model of IKs and its alpha-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the beta-subunit) confers kinetic properties on IKs that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand.ConclusionsBecause of its ability to form an available reserve, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.
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