Factor For Arrhythmias Research Articles

Characterization of an N-terminal Nav1.5 channel variant \u2013 a potential risk factor for arrhythmias and sudden death?

BackgroundAlterations in the SCN5A gene encoding the cardiac sodium channel Nav1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance.MethodsMutant as well as wild type GFP tagged Nav1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique.ResultsElectrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Nav1.5 current over the entire voltage window.ConclusionThe results support the assumption that the detected sequence aberration alters Nav1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.

Effects of a high-fat diet on intracellular calcium (Ca2+) handling and cardiac remodeling in Wistar rats without hyperlipidemia

ABSTRACT A high-fat diet is often associated with cardiovascular diseases. Research has suggested that consumption of a high-fat diet for 10 weeks is associated with cardiac dysfunction, including arrhythmias, through alterations in cardiac remodeling and myocardial intracellular calcium (Ca2+) handling. In this study, rats were randomly divided into two groups: the standard diet (N = 5) and high-fat diet (N = 5) groups. To evaluate the effects of a high-fat diet on cardiac remodeling, we investigated the myocardium obtained from male Wistar rats fed a high-fat diet or standard diet for ten weeks via scanning electron microscopy, polarization microscopy, and RT-PCR. We found that compared with the standard diet cohort, the high-fat diet cohort exhibited increased levels of SERCA2a and SERCA2b mRNA and a decreased level of PLB mRNA (P < .05). These findings showed that a high-fat diet may lead to cardiac upregulation of Ca2+ transport-related genes in the sarcoplasmic reticulum. Additionally, we observed endocardial injury accompanied by focal dense layered collagen, increased spacing between endocardial cells that was often filled with collagen debris, and increased amounts of collagen fibers among enlarged cardiomyocytes in the high-fat diet cohort. The abnormal intracellular calcium (Ca2+) handling and cardiac remodeling may be contributing factors in arrhythmias and sudden cardiac death in high-fat diet-fed rats.

Роль психоэмоциональных нагрузок в возникновении нарушений ритма сердца

Objective: to determine the prevalence of cardiac arrhythmias in the structure of visits to the cardiologist. Materials and methods: within two years a doctor-cardiologist turned 4373 patients. 652 of them had arrhythmia (522 men and 130 women), that was 14.9% of those who applied for medical assistance. There were some patients (545) among 652 participants, who had significant rhythm disturbance according to the Holter ECG, the number of ventricular and supraventricular extrasystoles exceeded the acceptable rate. These patients were divided into 3 groups to assess the frequency of ventricular and supraventricular arrhythmias: Group 1: patients with a primary rhythm disturbance according to the type of ventricular arrhythmia – 96 people (80 men and 16 women). Their average age was 68 years (18–89). Group 2: patients with a primary rhythm disturbance according to the type of supraventricular extrasystole – 343 people (271 men and 72 women). Their average age was 67 years (17–83).Group 3: patients with complex arrhythmias (supraventricular and ventricular premature beats) – 106 patients (94 men and 12 women). Their average age was 65 years (18–87). Compulsory medical examination for the patient included a complete medical examination with the filling of a formalized medical history; laboratory studies (clinical blood analysis, biochemical blood-potassium, sodium, magnesium, chlorine, glucose, lipid spectrum, creatinine, total protein, coagulation profile, thyroid hormones T3, T4, TTG); instrumental examinations (ECG, daily monitoring of Holter ECG, radiography of the chest, echocardiography). 48 patients (8.84 %) had no apparent causes of arrhythmias. These patients were directed to magnetic resonance imaging (MRI) of the heart for the purpose of clarifying the nature of the arrhythmia. Results: the prevalence of cardiac arrhythmias in the structure of visits to the cardiologist was 14.9%. The main etiological factors of arrhythmia were: ischemic heart disease (IHD) and arterial hypertension (AH). In the group with supraventricular arrhythmias, patients with a history of pulmonary embolism, heart failure II–IV FC, permanent cardiac pacing, oncology, thyroid disease (hyperthyroidism), hyperkalemia and hypercholesterolemia as well as exacerbation of diseases of the gastrointestinal tract were much more likely to meet. In the group with combined rhythm disturbances, patients with acquired heart defects and hypercholesterolemia were dominating; and in the group with ventricular arrhythmias, there were more patients with a prosthetic aortic valve. In the group with ventricular arrhythmias, smokers with burdened heredity in CAD were significantly more likely to meet, and in the group with supraventricular arrhythmias, there were significantly more women in the state of early perimenopause. The main provoking factor was a psycho-emotional stress. Conclusions: the identification of the nature of arrhythmias according to traditional methods was difficult in 48 patients (8.84%), MRI of the heart allowed to establish probable cause rhythm disturbances in 32 patients in this category (2/3 of all surveyed). This draws attention to the high frequency of detection of MRI signs of myocarditis (1/3 of the surveyed).

Early Postoperative Arrhythmias after Paediatric Cardiac Surgery

Background: The radical change in techniques in paediatric cardiac surgery has dramatically reduced the morbidity and mortality. The different varieties of arrhythmia that are frequently observed in postoperative period in our country are still not well documented.Objectives: To determine the incidence and risk factors of arrhythmia immediately after cardiac surgery in paediatric age group.Materials and method: It was a prospective study. A total of 100 paediatric patients (age &lt;18 years) who underwent cardiac surgery at Dhaka Shishu Hospital between 2013 and 2016 were selected purposivelyResults: Out of 100 patients maximum 41% were from 13-72 months age group. The mean age was 49.73±37.17 months with range of 0.5-231 months, 58% patients were male and rest were female. Postoperatively 31% subjects were arrhythmic and of these the highest number of patients suffered from junctional ectopic tachycardia. Out of these 100 patients, 39% were diagnosed as VSD followed by TOF (35%). Among 31 arrhythmic patients 59.83%, 41.93% and 3.22% manifested onset of arrhythmia at 1st, 1st to 2nd and 2nd to 7th postoperative period respectively. In this study age, body weight, cyanosis, CPB time, postoperative acidosis, ventilation support days, hypertension on arrival in ICU as well as ICU stay days were recognized as significant risk factors (p &lt;0.05).Conclusion: Proper and careful monitoring of younger patient with lower body weight undergoing corrective cardiac surgery with long cardiopulmonary bypass (CPB) time may reduce the episodes of post operative arrhythmia. These patients may require high inotropic support post operatively. So, medical prevention and early diagnosis as well as proper management may improve the operative outcome.Delta Med Col J. Jan 2018 6(1): 22-28

Influence of RyR2 Inhibition Kinetics on Calcium Sparks and Waves in a 3D Model of a Cardiac Cell

Although excess Ca2+ release through RyR2 in diastole is a key factor in arrhythmia, not all RyR2 antagonists have an antiarrhythmic action. Flecainide, carvedilol and dantrolene are RyR2 inhibitors with an anti-arrhythmic blocking action whereas tetracaine is a RyR2 inhibitor with a pro-arrhythmic action. Block by these agents is known to have different RyR2 blocking kinetics and different effects on Ca2+ sparks and waves. However, it is not clear how the different RyR2 blocking kinetics produce different calcium release properties in intact cells.We have developed a 3D model of Ca2+ dynamics, which is based on realistic morphological parameters and RyR2 kinetics. By including different kinetic models for block of RyR2, we find that open state block of RyR2 stabilises Ca2+ release. In contrast, the closed state block of RyR2 has the effect of increasing the positive feedback of Ca2+ on SR Ca2+ release; the net result is an increase in the amplitude of Ca2+ sparks, destabilization of SR Ca2+ cycling.

Anti-Arrhythmic Block of Ryr2 by Flecainide Versus Pro-Arrhythmic Block by Tetracaine in a 3D Model of a Cardiac Cell

Although excess Ca2+ release through RyR2 in diastole is a key factor in arrhythmia, not all RyR2 antagonists have an antiarrhythmic action. Our previous studies comparing the anti-arrhythmic blocking action of flecainide with the pro-arrhythmic blocking action of tetracaine found that flecainide reduced the amount of Ca2+ released during localised diastolic release events (Ca2+ sparks) but increased their frequency. As a result, flecainide had no effect on overall SR Ca2+ leak or SR Ca2+ content. However, the likelihood that each Ca2+ spark could generate an arrhythmogenic Ca2+ wave was reduced because the Ca2+ sparks were smaller. In contrast, tetracaine decreased spark-mediated SR Ca2+ leak but significantly increased SR Ca2+ content, Ca2+ released during a spark and frequency of Ca2+ waves. These results suggested that the flecainide-induced reduction in Ca2+ spark size contributes to its anti-arrhythmic action by reducing the probability of saltatory wave propagation between adjacent Ca2+ release sites. We developed 3D models of Ca2+ dynamics, which are linked to whole cell ionic current models of ventricular and sinoatrial node. By including a kinetic model for tetracaine and flecainide block of RyR2, we find that open state block of flecainide stabilises Ca2+ release. In contrast, the closed state block by tetracaine has the effect of increasing the positive feedback of Ca2+ on SR Ca2+ release; the net result is an increase in the amplitude of Ca2+ sparks, destabilization of SR Ca2+ cycling and cardiac arrhythmia.

Pulmonary Valve Preservation Strategies for Tetralogy of Fallot Repair

was affirmed in a significant number of patients who tolerated the persistent effects of right ventricular volume overload for many years. In a significant number of postoperative patients, however, long-term complications of pulmonary regurgitation, residual ventricular septal defects (VSD), distal pulmonary artery stenosis, right ventricular dysfunction, atrial or ventricular arrhythmias, and exercise intolerance 2-5 required further operative intervention to address the residual defects, perform concomitant arrhythmia surgery, and pulmonary valve insertion.

Genetic Polymorphisms and Haplotypes of the Human Cardiac Sodium Channel α Subunit Gene (SCN5A) in Japanese and their Association with Arrhythmia

Genetic variations in cardiac ion channels have been implicated not only as the causes of inherited arrhythmic syndromes, but also as genetic risk factors for some acquired arrhythmias. To elucidate the potential roles of genetic polymorphisms of the alpha subunit of the voltage-gated sodium channel type V (SCN5A) in cardiac rhythm disturbance, the entire SCN5A coding exons and their flanking introns were sequenced in 166 Japanese arrhythmic patients and 232 healthy controls. We detected 69 genetic variations, including 54 novel ones. Out of the 12 novel nonsynonymous single nucleotide polymorphisms (SNPs), p.Leu1988Arg was found at a frequency of 0.015. The other 11 SNPs were rare (0.001), with 6 found in arrhythmic patients and 5 in healthy controls. The frequency of a novel intronic SNP, c.703+130G>A, was significantly higher in the patients than in the controls, suggesting this SNP is associated with an unknown risk factor for arrhythmia. Following linkage disequilibrium analysis, the haplotype structure of SCN5A was inferred using high-frequency SNPs. The frequency of the haplotype harbouring both p.Leu1988Arg and the common SNP p.His558Arg (haplotype GG) was significantly lower in the patients than in the controls. This finding suggests that this haplotype (GG) might have been positively selected in the controls because of its protective effect against arrhythmias. This study provides fundamental information necessary to elucidate the effect of genetic variations in SCN5A on channel function and cardiac rhythm in Japanese, and probably in the Asian population.

Left Ventricular Hypertrophy as a Risk Factor for Arrhythmias in Hemodialysis Patients

The contribution of left ventricular hypertrophy in determining ventricular arrhythmias (VAS) was studied in 81 chronic renal failure patients in chronic hemodialysis using two-dimensional echocardiographic and electrocardiogram Holter monitoring. The prevalence of LVH was 93% (96% in hypertensive and 87% in normotensive patients). The prevalence of VA was 48%. These arrhythmias were associated with increased cardiac mass, lack of potassium supplementation to the hemodialysis bath, and low K+ and PaO2 during dialysis. Severe forms of VA occurred in 19 of 78 patients, and the risk factors for this occurrence were (a) largely increased cardiac mass indices (exceeding in more than 40% the upper limit of normal for each sex) and (b) prolonged periods of time in hemodialysis treatment (34 +/- 5.5 vs. 17 +/- 2.7 months, p less than 0.05). Changes in potassium or oxygen content of the blood were not significantly associated with the occurrence of severe forms of VA.

Cardiac Arrhythmias and Left Ventricular Function in Respiratory Failure from Chronic Obstructive Pulmonary Disease

In 22 patients with COPD, we studied the relationship between left ventricular function and cardiac arrhythmias. Ventricular arrhythmias were detected on a 24-h ECG recorded at the beginning of the observation period and after a stable improvement of RF. Left ventricular function was evaluated by equilibrium-gated radionuclide angiocardiography measuring LVEF, PER and PFR. We found a significant decrease in the arrhythmia score after improvement of RF; LVEF and PFR were slightly depressed in six and nine patients, respectively. A "step-up" multiple regression analysis revealed a significant inverse correlation between PFR and ventricular arrhythmias during worsened RF, whereas LVEF, arterial blood gases and clinical data were not significantly predictive variables. Thus, a depressed left ventricular diastolic performance seems to be a predictive factor for arrhythmias during RF from COPD. The poor definition of the statistical model suggests that other presently unknown factors contribute to the genesis of ventricular arrhythmias.

Left Ventricular Hypertrophy as a Factor in Arrhythmias and Sudden Death

Hypertensive patients with left ventricular hypertrophy (LVH) are predisposed to sudden cardiac death. Several studies have demonstrated that complex ventricular arrhythmias, including episodes of nonsustained ventricular tachycardia, occur commonly during ambulatory electrocardiographic monitoring of hypertensive patients with LVH. The prognostic significance of such arrhythmias is not known. In other forms of cardiac hypertrophy, however, such as hypertrophic cardiomyopathy, complex ventricular arrhythmias detected during ambulatory monitoring are predictive of subsequent sudden death and there is some evidence that appropriate antiarrhythmic drug therapy may reduce mortality.

Exercise testing in patients with life-threatening ventricular tachyarrhythmias: Results and correlation with clinical and arrhythmia factors

The results of exercise treadmill stress testing were analyzed in 64 consecutive patients presenting with either ventricular fibrillation (42%) or hemodynamically significant ventricular tachycardia (58%). Underlying diseases included coronary artery disease (55%), dilated cardiomyopathy (16%), and miscellaneous disorders (29%). Patients were additionally studied with ambulatory electrocardiographic monitoring and programmed stimulation. During exercise testing, 22 patients (34%) had nonsustained and five (8%) had sustained ventricular tachycardia. No patient experienced ventricular fibrillation or a major complication during exercise testing. Patients with a history of ventricular fibrillation were significantly less likely to have exercise-induced ventricular tachycardia than those with a history of ventricular tachycardia. Other clinical factors were not associated with the results of exercise testing. The results of programmed stimulation did not correlate with the results of exercise testing. Ventricular tachycardia was commonly documented during ambulatory monitoring (72%), but this was not predictive of ventricular tachycardia during exercise. However, patients who did not have ventricular tachycardia during ambulatory monitoring were predictably unlikely to have it during exercise testing ( p < 0.002). Thus exercise testing is safe and can provoke ventricular tachycardia in a significant proportion of patients with life-threatening arrhythmias.

Arrhythmias as predictors of sudden death

Two methods are available for exploring arrhythmias in cardiac patients who are at risk of sudden death: Holter monitoring and invasive electrophysiology. Despite numerous studies, the predictive value of these techniques, in terms of prognosis, remains poor for many reasons. Neither technique considered individually can give reliable prognostic indications simply because each technique addresses different issues which are only partially involved in the mechanism of sudden death. Invasive electrophysiology, by artificially provoking an arrhythmia, detects the potential substrate which may ultimately lead to lethal arrhythmias. Although this is an important technique it is insufficient because merely identifying the substrate for an arrhythmia does not necessarily mean that arrhythmia will occur. On the other hand, ambulatory ECG allows monitoring of spontaneous arrhythmias which may be considered as potential initiating factors in arrhythmias. However, even if initiating factors and potential substrates are present, they are not sufficient conditions to cause lethal arrhythmias to occur. When there is an opportunity to scrutinize the mechanism of arrhythmias which are indeed lethal, as in sudden death, it appears that the lethal event results from the intervention of a new factor which was either absent or not considered during preceding investigations. In coronary patients, curiously, ischemia more often provokes cardiac arrest or an electromechanical dissociation rather than a ventricular tachycardia or fibrillation. Sudden death is not infrequently of iatrogenic origin, because of the arrhythmogenic effect of powerful antiarrhythmic drugs. More important, ventricular fibrillation often occurs in the setting of a progressively increased sympathetic tone, which explains either the particular seriousness of a previously known arrhythmia or the occurrence of an arrhythmia which was never before observed. Consideration of this third factor, that is, the autonomic nervous system and its potential role in spontaneous and inducible arrhythmias, would certainly increase the accuracy of our modes of investigation and would explain the preventive effects of beta blockers with regard to the occurrence of sudden death.

Alterations of Long-Chain Free Fatty Acid and Magnesium Concentrations in Acute Myocardial Infarction

Sixteen patients with acute myocardial infarction were subjects of a study of the changes in plasma magnesium and long-chain free fatty acid (FFA) levels. In each patient, there was a sharp fall of magnesium levels and a sharp rise of FFA levels shortly after onset of pain. Magnesium and FFA values returned to normal within three days. An absolute fall in total magnesium level and a probable fall in magnesium ion concentration could be important factors in arrhythmias during the first two days. The simultaneous rise in FFA and fall in magnesium levels in a variety of pathologic and physiologic conditions affords an explanation for divergent changes in FFA and magnesium concentrations in acute myocardial infarction. The FFA rise appears to be the fall in magnesium levels, which has been previously unexplained.

Beta adrenergic and muscarinic cholinergic receptors in canine myocardium. Effects of ischemia.

Experimental myocardial ischemia produced in dogs by proximal left anterior descending coronary artery ligation is accompanied by relatively rapid (1 h) increases in the number of (-) [3H]dihydroalprenolol binding sites without changing their dissociation constants in ischemic left ventricular tissue. The changes, persist for at least 8 h and are accompanied by marked decreases in myocardial tissue ischemic region norepinephrine content. In contrast, in the same canine model 1 h of proximal left anterior descending coronary artery ligation did not result in a significant change in the number of [3H]quinuclidynl benzilate binding sites of their dissociation constants. However, the number of [3H]quinuclidynl benzilate binding sites (muscarinic cholinergic receptors) are 50--70% greater than (-) [3H]dihydroalprenolol binding sites (beta adrenergic receptors) in canine left ventricular tissue. Thus, the data suggest that proximal left anterior descending coronary artery occlusion for 1 h significantly increases the number of beta adrenergic receptors in ischemic left ventricular tissue without changing the number of muscarinic cholinergic receptors. Whether the ischemia-produced increase in cardiac beta-receptor content is causally related to increased cyclic AMP levels that develop in ischemic tissue and/or an etiologic factor in arrhythmias originating from ischemic myocardial tissue will have to be determined in additional studies.