Our purpose was to evaluate the efficacy of antiarrhythmic drugs (AADs) in recurrent ventricular fibrillation (VF) associated with inferolateral early repolarization pattern on the electrocardiogram.
...Although an implantable cardioverter-defibrillator is the treatment of choice, additional AADs may be necessary to prevent frequent episodes of VF and reduce implantable cardioverter-defibrillator shock burden or as a lifesaving therapy in electrical storms.
From a multicenter cohort of 122 patients (90 male subjects, age 37 +/- 12 years) with idiopathic VF and early repolarization abnormality in the inferolateral leads, we selected all patients with more than 3 episodes of VF (multiple) including those with electrical storms (> or =3 VF in 24 h). The choice of AAD was decided by individual physicians. Follow-up data were obtained for all patients using monitoring with implantable defibrillator. Successful oral AAD was defined as elimination of all recurrences of VF with a minimal follow-up period of 12 months.
Multiple episodes of VF were observed in 33 (27%) patients. Electrical storms (34 +/- 47 episodes) occurred in 16 and were unresponsive to beta-blockers (11 of 11), lidocaine/mexiletine (9 of 9), and verapamil (3 of 3), while amiodarone was partially effective (3 of 10). In contrast, isoproterenol infusion immediately suppressed electrical storms in 7 of 7 patients. Over a follow-up of 69 +/- 58 months, oral AADs were poorly effective in preventing recurrent VF: beta-blockers (2 of 16), verapamil (0 of 4), mexiletine (0 of 4), amiodarone (1 of 7), and class 1C AADs (2 of 9). Quinidine was successful in 9 of 9 patients, decreasing recurrent VF from 33 +/- 35 episodes to nil for 25 +/- 18 months. In addition, quinidine restored a normal electrocardiogram.
Multiple recurrences of VF occurred in 27% of patients with early repolarization abnormality and may be life threatening. Isoproterenol in acute cases and quinidine in chronic cases are effective AADs.
Purpose
Kv1.3 channel regulates the activity of lymphocytes, macrophages, or adipose tissue and its blockade reduces inflammatory cytokine secretion and improves insulin sensitivity in animals with ...metabolic syndrome and in genetically obese mice. Thus, Kv1.3 blockade could be a strategy for the treatment of type 2 diabetes. Elevated circulating levels of TNFα and IL-1b mediate the higher susceptibility to cardiac arrhythmia in type 2 diabetic rats. We hypothesized that Kv1.3 channel blockade with the psoralen PAP1 could have immunomodulatory properties that prevent QTc prolongation and reduce the risk of arrhythmia in type 2 diabetic rats.
Methods
Type 2 diabetes was induced to Sprague-Dawley rats by high-fat diet and streptozotocin injection. Diabetic animals were untreated, treated with metformin, or treated with PAP1 for 4 weeks. Plasma glucose, insulin, cholesterol, triglycerides, and cytokine levels were measured using commercial kits. ECG were recorded weekly, and an arrhythmia-inducing protocol was performed at the end of the experimental period. Action potentials were recorded in isolated ventricular cardiomyocytes.
Results
In diabetic animals, PAP1 normalized glycaemia, insulin resistance, adiposity, and lipid profile. In addition, PAP1 prevented the diabetes-induced repolarization defects through reducing the secretion of the inflammatory cytokines IL-10, IL-12p70, GM-CSF, IFNγ, and TNFα. Moreover, compared to diabetic untreated and metformin-treated animals, those treated with PAP1 had the lowest risk of developing the life-threatening arrhythmia
Torsade de Pointes
under cardiac challenge.
Conclusion
Kv1.3 inhibition improves diabetes and diabetes-associated low-grade inflammation and cardiac electrical remodeling, resulting in more protection against cardiac arrhythmia compared to metformin.
Background/Aims: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid ...(GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. Materials and Methods: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). Results: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. Conclusion: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.
IntroductionImplantable cardioverter-defibrillators (ICDs) can prevent sudden cardiac death due to ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The ...aim of our study was to assess the cumulative burden, evolution and potential triggers of appropriate ICD shocks during long-term follow-up, which may help to reduce and further refine individual arrhythmic risk in this challenging disease.MethodsThis retrospective cohort study included 53 patients with definite ARVC according to the 2010 Task Force Criteria from the multicentre Swiss ARVC Registry with an implanted ICD for primary or secondary prevention. Follow-up was conducted by assessing all available patient records from patient visits, hospitalisations, blood samples, genetic analysis, as well as device interrogation and tracings.ResultsFifty-three patients (male 71.7%, mean age 43±2.2 years, genotype positive 58.5%) were analysed during a median follow-up of 7.9 (IQR 10) years. In 29 (54.7%) patients, 177 appropriate ICD shocks associated with 71 shock episodes occurred. Median time to first appropriate ICD shock was 2.8 (IQR 3.6) years. Long-term risk of shocks remained high throughout long-term follow-up. Shock episodes occurred mainly during daytime (91.5%, n=65) and without seasonal preference. We identified potentially reversible triggers in 56 of 71 (78.9%) appropriate shock episodes, the main triggers representing physical activity, inflammation and hypokalaemia.ConclusionThe long-term risk of appropriate ICD shocks in patients with ARVC remains high during long-term follow-up. Ventricular arrhythmias occur more often during daytime, without seasonal preference. Reversible triggers are frequent with the most common triggers for appropriate ICD shocks being physical activity, inflammation and hypokalaemia in this patient population.
Voltage-gated potassium (Kv) channels control myocardial repolarization. Pore-forming Kvα proteins associate with intracellular Kvβ subunits, which bind pyridine nucleotides with high affinity and ...differentially regulate channel trafficking, plasmalemmal localization and gating properties. Nevertheless, it is unclear how Kvβ subunits regulate myocardial K+ currents and repolarization. Here, we tested the hypothesis that Kvβ2 subunits regulate the expression of myocardial Kv channels and confer redox sensitivity to Kv current and cardiac repolarization. Co-immunoprecipitation and in situ proximity ligation showed that in cardiac myocytes, Kvβ2 interacts with Kv1.4, Kv1.5, Kv4.2, and Kv4.3. Cardiac myocytes from mice lacking Kcnab2 (Kvβ2−/−) had smaller cross sectional areas, reduced sarcolemmal abundance of Kvα binding partners, reduced Ito, IK,slow1, and IK,slow2 densities, and prolonged action potential duration compared with myocytes from wild type mice. These differences in Kvβ2−/− mice were associated with greater P wave duration and QT interval in electrocardiograms, and lower ejection fraction, fractional shortening, and left ventricular mass in echocardiographic and morphological assessments. Direct intracellular dialysis with a high NAD(P)H:NAD(P)+ accelerated Kv inactivation in wild type, but not Kvβ2−/− myocytes. Furthermore, elevated extracellular levels of lactate increased NADHi and prolonged action potential duration in wild type cardiac myocytes and perfused wild type, but not Kvβ2−/−, hearts. Taken together, these results suggest that Kvβ2 regulates myocardial electrical activity by supporting the functional expression of proteins that generate Ito and IK,slow, and imparting redox and metabolic sensitivity to Kv channels, thereby coupling cardiac repolarization to myocyte metabolism.
•Kv auxiliary Kvβ2 subunits interact with Kv1 and Kv4 channels in the murine heart.•Ablation of Kvβ2 leads to suppression of Ito, IK,slow1 and IK,slow2, and prolongs action potential duration.•Pyridine nucleotide ratios simulating hypoxic conditions enhance Kv inactivation in wild type, but not Kvβ2−/− myocytes.•Lactate increases NADH:NAD+ ratio and prolongs action potential duration in wild type, but not Kvβ2−/− hearts.
Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly ...due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.
The impact of cardiac resynchronization therapy (CRT) on clinical outcome in patients with a continuous-flow left ventricular assist device (LVAD) is currently not well understood. We conducted a ...systematic literature review and meta-analysis with an intention to summarize all published clinical evidence. We searched MEDLINE and EMBASE databases through March 2018 for studies that compared the outcomes in patients with LVAD and CRT. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects model, inverse variance method. The between-study heterogeneity was assessed using the
Q
statistic and
I
2
. A total of seven studies that included 1157 (575 CRT; 582 non-CRT) patients were identified. Our meta-analysis did not demonstrate a significant difference in the risk of mortality (pooled OR = 1.21, 95% CI 0.90–1.63,
P
= 0.21), ventricular arrhythmia incidence (pooled OR = 1.36, 95% CI 0.99–1.86,
P
= 0.06), hospitalization (pooled OR = 1.36, 95% CI 0.59–3.14,
P
= 0.48), or implantable cardioverter defibrillator therapies (pooled OR = 1.08, 95% CI 0.51–2.30,
P
= 0.84) among the CRT group compared with the non-CRT group. There was high heterogeneity with an
I
2
of 75% for ICD therapies. Among LVAD patients, CRT combined did not significantly affect mortality, re-hospitalization, ventricular arrhythmia incidence, and ICD therapies.
We present the results from a white-box machine learning approach to detect cardiac arrhythmias using electrocardiographic data. A C5.0 is trained to recognize four classes using common features. The ...four classes are (i) atrial fibrillation and atrial flutter, (ii) tachycardias (iii), sinus bradycardia and (iv) sinus rhythm. Data from 10,646 subjects, 83% of whom have at least one arrhythmia and 17% of whom exhibit a normal sinus rhythm, are used. The C5.0 is trained using 10-fold cross-validation and is able to achieve a balanced accuracy of 95.35%. By using the white-box machine learning approach, a clear and comprehensible tree structure can be revealed, which has selected the 5 most important features from a total of 24 features. These 5 features are ventricular rate, RR-Interval variation, atrial rate, age and difference between longest and shortest RR-Interval. The combination of ventricular rate, RR-Interval variation and atrial rate is especially relevant to achieve classification accuracy, which can be disclosed through the tree. The tree assigns unique values to distinguish the classes. These findings could be applied in medicine in the future. It can be shown that a white-box machine learning approach can reveal granular structures, thus confirming known linear relationships and also revealing nonlinear relationships. To highlight the strength of the C5.0 with respect to this structural revelation, the results of further white-box machine learning and black-box machine learning algorithms are presented.
Coronavirus disease 2019 (COVID-19) outbreak is a public health emergency of international concerns because of a highly pathogenic human coronavirus (HCoV), actually named severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2). Despite much emerging data about the epidemiological association between cardiovascular diseases and COVID-19, little is still known about atrial fibrillation and its optimal management in this clinical contest. The aim of our review is to describe the pharmacological interactions between cardiovascular drugs more commonly used in atrial fibrillation management and experimental COVID-19 therapies, based on EU and US summaries of product characteristics.
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