Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent.     

室性心律失常的基因诊疗

在一些发达国家,心脏骤停已成为最主要的死亡原因.快速性室性心律失常是导致心脏骤停最主要的原因,且快速性室性心律失常会增加结构性心脏病患者发病的风险.通过药物和器械治疗方法,存在较大的局限性.心脏电活动的细胞基础是动作电位.动作电位是由于时间和电压依赖性激活各种钠、钙和钾离子通道和泵产生的.心律失常机制包括折返,自律性异常和触发活动.折返是在组织水平发生的.异常的自动性和触发活动是细胞现象,能够存在于单个心肌细胞或细胞群.心律失常的发生就是上述电冲动传播从这个局部激动由细胞间传导至更多的心肌中.故研究人员提出开展基因治疗心律失常替代现有的治疗方法.在本文中,我们讨论应用基因治疗快速性室性心律失常的基本机制并总结方法.     

Evaluation of Left Ventricular Endocardial Cardiac Resynchronization Therapy in a Non-responder with Ventricular Arrhythmias

Approximately one third of patients treated with cardiac resynchronization therapy do not derive any detectable benefit. In these patients, acute invasive hemodynamic evaluation can be used for therapy optimization. This report describes the use of systematic invasive hemodynamic measurements for clinical decision making in a patient who experienced severe ventricular arrhythmias and clinical deterioration following a biventricular upgrade.     

Radiofrequency Catheter Ablation of Idiopathic Right Ventricular Outflow Tract Arrhythmias

Idiopathic ventricular arrhythmias (VA) consist of various subtypes of VA that occur in the absence of clinically apparent structural heart disease. Affected patients account for approximately 10% of all patients referred for evaluation of ventricular tachycardia (VT). Arrhythmias arising from the outflow tract (OT) are the most common subtype of idiopathic VA and more than 70–80% of idiopathic VTs or premature ventricular contractions (PVCs) originate from the right ventricular (RV) OT. Idiopathic OT arrhythmias are thought to be caused by adenosine-sensitive, cyclic adenosine monophosphate (cAMP) mediated triggered activity and, in general, manifest at a relatively early age. Usually they present as salvos of paroxysmal ventricular ectopic beats and are rarely life-threatening. When highly symptomatic and refractory to antiarrhythmic therapy or causative for ventricular dysfunction, ablation is a recommended treatment with a high success rate and a low risk of complications.     

Circadian Rhythms of Early Afterdepolarizations and Ventricular Arrhythmias in a Cardiomyocyte Model

Sudden cardiac arrest is a malfunction of the heart’s electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events are at least partially under the control of the endogenous circadian timekeeping system. However, the biophysical mechanisms linking molecular circadian clocks to cardiac arrhythmogenesis are not fully understood. Recent experiments have shown that L-type calcium channels exhibit circadian rhythms in both expression and function in guinea pig ventricular cardiomyocytes. We developed an electrophysiological model of these cells to simulate the effect of circadian variation in L-type calcium conductance. In our simulations, we found that there is a circadian pattern in the occurrence of early afterdepolarizations (EADs), which are abnormal depolarizations during the repolarization phase of a cardiac action potential that can trigger fatal ventricular arrhythmias. Specifically, the model produces EADs in the morning, but not at other times of day. We show that the model exhibits a codimension-2 Takens-Bogdanov bifurcation that serves as an organizing center for different types of EAD dynamics. We also simulated a two-dimensional spatial version of this model across a circadian cycle. We found that there is a circadian pattern in the breakup of spiral waves, which represents ventricular fibrillation in cardiac tissue. Specifically, the model produces spiral wave breakup in the morning, but not in the evening. Our computational study is the first, to our knowledge, to propose a link between circadian rhythms and EAD formation and suggests that the efficacy of drugs targeting EAD-mediated arrhythmias may depend on the time of day that they are administered.     

Development of Malignant Ventricular Arrhythmias in a Young Male with WPW Pattern

In Wolff-Parkinson-White Syndrome (WPW), presence of accessory pathways causes various tachyarrhythmias that lead to different symptoms and clinical conditions in patients. Atrial fibrillation is observed in about 20-30% of this group of patients. Life threatening malignant ventricular arrhythmias and sudden cardiac deaths are observed in patients having rapid conduction in accessory pathways and short antegrade refractory periods (<250 msn). We present a WPW syndrome case that presented to the emergency service with narrow QRS tachycardia and later developed malignant ventricular arrhythmia.     

Membrane Effects of the n-3 Fish Oil Fatty Acids,which Prevent Fatal Ventricular Arrhythmias

Fish oil fatty acids are known to exert beneficial effects on the heart and vascular systems. We have studied the membrane effects on ion channel conductance by the n-3 fish oil fatty acids that account for these beneficial effects. We have confirmed that these fatty acids prevent fatal cardiac arrhythmias in a reliable dog model of sudden cardiac death. This finding was followed by experiments indicating that the n-3 fatty acids electrically stabilize heart cells and do so largely through modulation of the fast voltage-dependent Na⁺ currents and the L-type Ca²⁺ channels in a manner, which makes the heart cells resistant to arrhythmias. Others and we have demonstrated that these membrane effects on the heart can prevent fatal cardiac arrhythmias in humans.     

The Chinese Neolithic: Recent Trends in Research

Early food production, featuring at least two and probably three separate suites of plants, occurred in at least six different regions in China. Gradually, the earliest stages of village life and plant-animal domestication are becoming clearer, and Chinese archeologists are attempting to reconstruct the societal context of these developments. Late Neolithic sites, shedding light on the indigenous evolution to state-level societies, are now being published, and the ethnohistoric links between archeological cultures and major ethnic groups are being considered. The volume of excavation and publication makes China one of the most exciting areas of Neolithic research at the present time. A discussion of major contributions and topics of debate follows.     

Bretylium Tosylate in the Management of Refractory Ventricular Fibrillation

Nine patients who had recurrent ventricular fibrillation following acute myocardial infarction or angina were given bretylium tosylate in a dose of 5 mg./kg. intramuscularly every eight hours after other measures had proved ineffective. Provided the patients were not in shock or in heart failure, there was a considerable reduction in the episodes of ventricular fibrillation.A second group of nine patients who developed recurrent ventricular fibrillation following open heart surgery were given bretylium intravenously, which controlled the arrhythmia in every instance.Bretylium did not completely abolish ventricular premature beats but the latter did not initiate ventricular fibrillation even when they occurred on the T wave.