C Antzelevitch

..The challenge ahead is to be able to identify those at risk for sudden cardiac death. Here I review the clinical and genetic aspects as well as the cellular and molecular mechanisms underlying the J wave syndromes...

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..We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death...

..In conclusion, long QT, short QT, Brugada, and catecholaminergic polymorphic VT syndromes are pathologies with very different phenotypes and etiologies, but they share a common final pathway in causing sudden cardiac death...

..This article reviews recent advances in our understanding of these mechanisms, particularly the role of TDR in the genesis of drug-induced TdP, and examines how these may guide us towards development of safer drugs...

..The purpose of this brief review is to chronicle the historical highlights that have brought us to our present understanding of Brugada syndrome...

..These actions also lead to a TDR that manifests as the Brugada syndrome in RV and the short QT syndrome in LV...

..This minireview briefly summarizes the progress made over the past decade in our understanding of the clinical, genetic, cellular, ionic, and molecular aspects of this disease...

..Although direct evidence in support of any of these three hypotheses is lacking, recent studies involving the short QT syndrome have generated renewed interest in the mechanoelectrical hypothesis...

..This brief review summarizes the key clinical and experimental milestones that have brought us to our current understanding and approach to therapy of the Brugada syndrome...

..Controversies with regard to risk stratification and newly proposed pharmacologic strategies are discussed...

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..Moreover, drugs such as sodium pentobarbital, which reduce transmural dispersion of repolarization, can diminish the likelihood of TdP, despite their ability to prolong the QT interval...

..Ranolazine's actions to reduce TDR and suppress early after depolarization suggest that in addition to its anti-anginal actions, the drug possesses antiarrhythmic activity...

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..The present study examines its electrophysiological effects in isolated canine ventricular myocytes, tissues, and arterially perfused left ventricular wedge preparations...

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..In conclusion, the long QT, short QT, Brugada and catecholaminergic VT syndromes are pathologies with very different phenotypes and aetiologies, but which share a common final pathway in causing sudden death...

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..This review also discusses the value of the interval between the peak and end of the T wave (T(peak)-T(end), T(p)-T(e)) as an index of SDR and transmural dispersion of repolarization, in particular...

..1999; Antzelevitch & Dumaine, 2000)...

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..These observations may explain the inability of earlier studies to detect the M cell...

..Therapy is directed at restoring the balance of current via inhibition of the transient outward current, Ito, and/or stimulation of inward calcium using beta adrenergic agonists, among several strategies...

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..This study sought to elucidate the cellular and ionic basts for erythromycin-induced long QT syndrome...

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..These issues are discussed in other articles. These concerns notwithstanding, it is important that we continue to question whether the economic inefficiencies of current screening methodologies supersede the value of a young life...

..This review summarizes the available data regarding the electrophysiologic actions and antiarrhythmic properties of ranolazine in preclinical and clinical studies...

..These findings suggest that atrial-selective sodium channel block may be a fruitful new strategy for the management of AF...

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..This article provides a brief overview of recent advances in our understanding of the clinical presentation and molecular and cellular mechanisms and an update of existing controversies...

..However, these syndromes share a common final pathway in their predisposition to sudden cardiac death...

..Our observations suggest that atrial-selective sodium channel block may be a fruitful strategy for the management of AF...

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..The available data suggest that that the principal problem with the long QT syndrome is not long QT intervals but rather the dispersion of repolarization that often accompanies prolongation of the QT interval...

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..2 resulting in gain of function of the L-type calcium current (I(Ca,L)). Ranolazine is an antianginal agent shown to exert an antiarrhythmic effect in experimental models of long QT syndrome...

..The increase in TDR creates the substrate for the development of torsade de pointes under long-QT conditions...

..To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation...

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..A large midmyocardial I(NaCa) may contribute to the prolonged action potential of these cells as well as to the development of triggered activity under calcium-loading conditions...

..The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females...

..In conclusion, AZD1305 exerts atrial predominant sodium channel-blocking effects in vitro and in vivo and effectively suppresses AF...

..The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome...

..CONCLUSION: Our results indicate that chromanol 293B is a relatively selective blocker of I(Ks) in canine left ventricular myocytes...

..Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG...

..Our findings suggest that atrial-selective sodium channel block may be a valuable strategy to combat AF...

..Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry...

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..Short QT syndrome (SQTS) is a primary electrical disease of the heart associated with a high risk of sudden cardiac death. A gain-of-function in I(Kr), due to a mutation in KCNH2, underlies SQT1...

..The data highlight the critical importance of I(Ks) in the canine heart and the significant role of electrotonic interactions in minimizing the development of an arrhythmogenic substrate when repolarization reserve is reduced...

..Epicardial, M region, and endocardial tissues and cells show distinct, sometimes opposite, responses to a variety of drugs, including those capable of inducing EADs and DADs...

..More importantly, drugs that slow inactivation of sodium channels will produce a nonuniform response across the ventricular wall that is proarrhythmic...

..Although amiodarone is one of the most effective pharmacologic agents used in clinical management of atrial fibrillation (AF), little is known about its differential effects in atrial and ventricular myocardium...

..This study tests the hypothesis that their combined actions synergistically depress I(Na)-dependent parameters in atria but not ventricles...

..Epicardial origin of the ectopic beats increases transmural dispersion of repolarization, thus providing the substrate for the development of reentrant tachyarrhythmias that underlie rapid polymorphic VT/VF...

..Afterdepolarization-induced triggered activity was never observed in the epicardial or endocardial layers...

..In the absence of ST-segment elevation at baseline, family members with first-degree atrioventricular block should be suspected of carrying the mutation. An ajmaline test is often the key to making the proper diagnosis in these patients...

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..The aim of this study was to evaluate the effectiveness of a combination of dronedarone and ranolazine in suppression of atrial fibrillation (AF)...

..The mechanisms responsible for the development of one without the other are poorly understood...

..The present study examines the electrophysiological actions of cisapride in the isolated arterially perfused canine left ventricular wedge preparation...

..Ectopic activity arising from the pulmonary veins (PV) plays a prominent role in the development of atrial fibrillation (AF)...

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..Short QT (SQT) syndrome (SQT) 1 is an inherited sudden death syndrome often associated with atrial fibrillation (AF). We examined the cellular basis for AF in a newly developed experimental atrial model of SQT1...

..These findings suggest caution when treating patients carrying such genetic variations with Class I antiarrhythmic drugs...

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..These preliminary studies provide support for the hypothesis that there is a genetic predisposition to the type and severity of arrhythmias that develop during and after an AMI, and that additional studies are warranted...

..Although these distinctions are conferred in part by differences in electrical characteristics of the three cell types, intrinsic differences in excitation-contraction coupling are evident...

..At the center of the controversy is the issue as to which of the two electrodes is the recording electrode and which is the indifferent electrode. The present study is designed to address this issue...

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..We report the first BrS mutation in CaCNB2b resulting in accelerated inactivation of L-type calcium channel current. Our results suggest that the faster current decay results in a loss-of-function responsible for the Brugada phenotype..

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..The present study describes the genetic basis for a new clinical entity characterized by sudden death and short-QT intervals in the ECG...

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..A major focus will be on the ability of the atrial-selective sodium channel blocking properties of these agents, possibly in conjunction with I Kur and/or I Kr blocking properties, to suppress and prevent the reinduction of AF...

..There are no full-length published reports describing the effectiveness of acute dronedarone use against AF in experimental or clinical studies...

..This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A...

..However, it has been shown that I(Kur) block may abbreviate atrial repolarization and that loss-of-function mutations in KCNA5, which encodes K(v) 1.5 channels responsible for I(Kur), is associated with familial AF...

..The present study examines the effect of hyperthermia on transmural dispersion of action potential duration (TD-APD), early afterdepolarization (EAD) activity, and torsade de pointes (TdP) under long-QT conditions...

..In this brief review, our goal is to summarize the molecular mechanisms proposed to underlie the susceptibility to arrhythmias in LQTS and discuss the direction of current and future research...

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..The cellular mechanisms involved are not well-defined and are the subject of this investigation...

..We hypothesized that this action would be antiarrhythmic in the setting of Brugada syndrome...

..Our study also points to major differences in the transmembrane activity recorded using superfused vs. arterially perfused atrial preparations...

..This review briefly describes the mechanisms and properties of late-phase 3 EADs, how they differ from conventional EADs and DADs, as well as their role in the initiation of cardiac arrhythmias, such as atrial fibrillation...

..The cellular and ionic basis for coarse versus fine AF is not well delineated...

..Scarce information on the cellular components of the intrinsic cardiac ganglia from higher mammals has limited our understanding of the role of the autonomic nervous system in such diseases...

..We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A. The proband inherited 1 mutation from each parent and transmitted 1 to each daughter...

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..The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF)...

..However, the trigger that initiates reentry remains unknown. We studied the initiation of reentry attending the development of electrical heterogeneity during simulated ischemia in isolated canine right ventricular subepicardium...

..Amplification of intrinsic electrical heterogeneities provides the substrate responsible for developing Phase 2 and circus movement reentry, which underlie ventricular tachycardia in the long QT and Brugada syndromes...

..Our long-range goal is to generate information that will contribute meaningfully to our understanding of arrhythmic death in infants and young children. ..

..Our long-range goal is to generate information that will contribute to our understanding of the causes for arrhythmic death in infants and young children. ..

..The long range goal is to generate information that will contribute to a more definitive and less empiric approach in the medical management of cardiac arrhythmias and sudden cardiac death. ..

..Our long-range goal is to narrow the gap that currently exists in this area and to generate information that will contribute to a more definitive and less empiric approach in the medical management of cardiac arrhythmias...

..Successful completion of the studies proposed in this competing renewal will significantly advance this goal and lead to the development of innovative and effective pharmacologic treatments for AF. ..