Flecainide‐Associated Bradycardia‐Dependent Torsade de Pointes: Another Potential Mechanism of Proarrhythmia

Kim, Han Sang; Pak, Hui Nam; Park, Jong Seoung; Kim, Sung Soon

doi:10.1111/j.1540-8159.2010.02935.x

Cited by 10 publications

(7 citation statements)

References 9 publications

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“…In human patients, flecainide increases the RV monophasic action potential duration and prolongs QT interval . Arrhythmogenic responses to flecainide are facilitated in the presence of well‐known torsadogenic risk factors, such as bradycardia, hypokalaemia, and previously unsuspected long QT syndrome gene mutations, which is in support of the role played by reduced repolarization reserve in adverse effects associated with flecainide therapy.…”

Section: Arrhythmogenic Responses To Antiarrhythmic Drugsmentioning

confidence: 68%

“…Flecainide, nevertheless, remains one of the first‐line treatments for symptomatic atrial fibrillation in patients with structurally normal hearts . This practice, however, is increasingly challenged by clinical observations indicating that flecainide can induce VT, often in the form of torsade de pointes, in patients without coronary artery disease or severe heart failure . The Pediatric Electrophysiology Group reported on the relatively high incidence of flecainide‐induced proarrhythmia in young cardiac patients, presumably in the absence of advanced coronary atherosclerosis which is commonly seen in the elderly .…”

Section: Arrhythmogenic Responses To Antiarrhythmic Drugsmentioning

confidence: 99%

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Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

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In cardiac patients, life-threatening tachyarrhythmia is often precipitated by abnormal changes in ventricular repolarization and refractoriness. Repolarization abnormalities typically evolve as a consequence of impaired function of outward K currents in cardiac myocytes, which may be caused by genetic defects or result from various acquired pathophysiological conditions, including electrical remodelling in cardiac disease, ion channel modulation by clinically used pharmacological agents, and systemic electrolyte disorders seen in heart failure, such as hypokalaemia. Cardiac electrical instability attributed to abnormal repolarization relies on the complex interplay between a provocative arrhythmic trigger and vulnerable arrhythmic substrate, with a central role played by the excessive prolongation of ventricular action potential duration, impaired intracellular Ca handling, and slowed impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account for the dependence of arrhythmic vulnerability on the location of the ventricular pacing site. Finally, the review clarifies the electrophysiological basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the clinical importance and pathophysiology of drug-induced arrhythmia, with particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na channel blockers, and class III antiarrhythmic agents that block the delayed rectifier K channel (dofetilide).

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Section: Arrhythmogenic Responses To Antiarrhythmic Drugsmentioning

confidence: 68%

Section: Arrhythmogenic Responses To Antiarrhythmic Drugsmentioning

confidence: 99%

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

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“…A database literature search revealed only three such cases in patients with no additional triggers (electrolyte imbalance or medications). In all three cases, it was preceded by a bradyarrhythmia, perhaps providing the substrate for QT prolongation . Our patient was undergoing vigorous exercise and was unlikely to have been bradycardic; however, we cannot discount the fact that the effects of flecainide could have been enhanced by his exercise, leading to a transient bradycardia that served as the substrate for the development of his torsades de pointes.…”

Section: Discussionmentioning

confidence: 80%

“…Interestingly, our patient had a prolonged QT, most notably around the time of his cardiac arrest, without an associated increase in QRS duration as would be expected given flecainide's mechanism of action. There is a paucity of published information regarding the association of flecainide‐induced QT prolongation and the development of torsades de pointes in patients with a structurally normal heart . A database literature search revealed only three such cases in patients with no additional triggers (electrolyte imbalance or medications).…”

Section: Discussionmentioning

confidence: 99%

“…There is a paucity of published information regarding the association of flecainide-induced QT prolongation and the development of torsades de pointes in patients with a structurally normal heart. [16][17][18] A database literature search revealed only three such cases in patients with no additional triggers (electrolyte imbalance or medications). In all three cases, it was preceded by a bradyarrhythmia, perhaps providing the substrate for QT prolongation.…”

Section: E32mentioning

confidence: 99%

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An Unusual Case of Flecainide‐induced QT Prolongation Leading to Cardiac Arrest

et al. 2014

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Flecainide is recommended as a first-line antiarrhythmic drug to maintain normal sinus rhythm in patients with atrial fibrillation (AF) who have structurally normal hearts or hypertension without left ventricular hypertrophy. Flecainide is a sodium channel blocker with minimal effects expected on ventricular repolarization. We describe the case of a 32-year-old man with a structurally normal heart and persistent AF who was started on diltiazem and flecainide 50 mg twice/day approximately a year prior to presentation. Due to persistent and bothersome symptoms, his dose was increased to 150 mg twice/day, which was associated with a progressive lengthening of his corrected QT interval. On the day of presentation, he underwent an exercise test as part of his job requirements. While running, he felt lightheaded and experienced a syncopal event and cardiac arrest. An automated external defibrillator was available that displayed polymorphic ventricular tachycardia. The patient was successfully resuscitated. Although rare, this case suggests that flecainide can induce QT prolongation leading to torsades de pointes. Clinicians should be aware and consider periodic evaluations with electrocardiograms.

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Late Sodium Current Inhibition in Acquired and Inherited Ventricular (dys)function and Arrhythmias

Remme

Wilde

2013

Cardiovasc Drugs Ther

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The late sodium current has been increasingly recognized for its mechanistic role in various cardiovascular pathologies, including angina pectoris, myocardial ischemia, atrial fibrillation, heart failure and congenital long QT syndrome. Although relatively small in magnitude, the late sodium current (I(NaL)) represents a functionally relevant contributor to cardiomyocyte (electro)physiology. Many aspects of I(NaL) itself are as yet still unresolved, including its distribution and function in different cell types throughout the heart, and its regulation by sodium channel accessory proteins and intracellular signalling pathways. Its complexity is further increased by a close interrelationship with the peak sodium current and other ion currents, hindering the development of inhibitors with selective and specific properties. Thus, increased knowledge of the intricacies of the complex nature of I(NaL) during distinct cardiovascular conditions and its potential as a pharmacological target is essential. Here, we provide an overview of the functional and electrophysiological effects of late sodium current inhibition on the level of the ventricular myocyte, and its potential cardioprotective and anti-arrhythmic efficacy in the setting of acquired and inherited ventricular dysfunction and arrhythmias.

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Flecainide‐Associated Bradycardia‐Dependent Torsade de Pointes: Another Potential Mechanism of Proarrhythmia

Cited by 10 publications

References 9 publications

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

An Unusual Case of Flecainide‐induced QT Prolongation Leading to Cardiac Arrest

Late Sodium Current Inhibition in Acquired and Inherited Ventricular (dys)function and Arrhythmias

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