The effects of pure potassium channel blocker nifekalant and sodium channel blocker mexiletine on malignant ventricular tachyarrhythmias

doi:10.1016/j.jelectrocard.2016.09.005

Journal of Electrocardiology

Volume 50, Issue 3, May–June 2017, Pages 277-281

https://doi.org/10.1016/j.jelectrocard.2016.09.005 Get rights and content

Highlights

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Nifekalant completely suppressed recurrences of ventricular arrhythmias in 28 of 44 patients (64%).
•
The stepwise treatment with nifekalant and mexiletine was effective in preventing ventricular tachyarrhythmias in 33 of 44 patients (75%)
•
During follow-up, 8 patients had repetitive ventricular tachyarrhythmia recurrences, and the stepwise treatment was effective in 6 of these 8 patients (75%).

Abstract

Background

Patients with repetitive ventricular tachyarrhythmias — so-called electrical storm — frequently require antiarrhythmic drugs. Amiodarone is widely used for the treatment of electrical storm but is ineffective in some patients. Therefore, we investigated the efficacy of stepwise administration of nifekalant, a pure potassium channel blocker, and mexiletine for electrical storm.

Methods

This study included 44 patients with repetitive ventricular tachyarrhythmias who received stepwise therapy with nifekalant and mexiletine for electrical storm. Nifekalant was initially administered, and mexiletine was subsequently added if nifekalant failed to control ventricular tachyarrhythmias.

Results

Nifekalant completely suppressed recurrences of ventricular arrhythmias in 28 patients (64%), including 6 patients in whom oral amiodarone failed to control arrhythmias. In 9 of 16 patients in whom nifekalant was partially effective but failed to suppress ventricular arrhythmias, mexiletine was added. The addition of mexiletine prevented recurrences of ventricular tachyarrhythmias in 5 of these 9 patients (56%). There was no death associated with electrical storm. In total, the stepwise treatment with nifekalant and mexiletine was effective in preventing ventricular tachyarrhythmias in 33 of 44 patients (75%). There was no difference in cycle length of the ventricular tachycardia, QRS interval, QT interval, or left ventricular ejection fraction between patients who responded to antiarrhythmic drugs and those who did not. During follow-up, 8 patients had repetitive ventricular tachyarrhythmia recurrences, and the stepwise treatment was effective in 6 of these 8 patients (75%).

Conclusions

The stepwise treatment with nifekalant and mexiletine was highly effective in the suppression of electrical storm.

Introduction

An implantable cardioverter–defibrillator (ICD) is the first line treatment to prevent sudden cardiac death from ventricular tachyarrhythmias. More than half of patients with an ICD for secondary prevention of sudden cardiac death receive appropriate ICD therapy, but up to 23% of patients have repetitive episodes of ventricular tachyarrhythmias: so-called electrical storm [1], [2], [3].

Electrical storm is a life-threatening emergency and is associated with increased mortality. Therefore, antiarrhythmic drugs to suppress ventricular tachyarrhythmias are usually required when patients develop electrical storm. However, evidence showing the efficacy of antiarrhythmic drugs for frequent episodes of ventricular tachyarrhythmias or electrical storm is limited. Among the antiarrhythmic drugs, amiodarone, which affects various ion channels including potassium, sodium, and calcium channels, is one of the most effective drugs for ventricular tachyarrhythmias and is widely used to control electrical storm [4]. However, amiodarone is ineffective in some patients and is associated with increased risk of drug-related adverse effects compared with other antiarrhythmic drugs [5], [6]. Nifekalant is a pure potassium channel blocker, which mainly inhibits the rapid components of the delayed rectifier potassium current, and only intravenous formation is commercially available. Nifekalant has been effective in a limited number of patients with a severe form of electrical storm in prior studies and can be an alternative therapy [7], [8], [9]. Therefore, we investigated the efficacy of stepwise administration of nifekalant and the addition of the sodium channel blocker mexiletine when nifekalant alone failed to control ventricular tachyarrhythmias as an emergency treatment to control electrical storm.

Section snippets

Patients

This was a retrospective study, which included patients who developed electrical storm and received nifekalant therapy in order to treat electrical storm between January 1, 2006 and January 1, 2013 in our institution. Nifekalant was administered as a loading infusion of 0.1 to 0.3 mg/kg for 5 min followed by a maintenance dose of 0.05 to 0.4 mg/kg/h. If the QT or corrected QT interval was prolonged to more than 600 ms, the dose of nifekalant was decreased. The corrected QT interval was calculated

Results

This study included 44 patients who received nifekalant due to electrical storm (Table 1). The patients included 34 men (77%), aged 61 ± 15 years (range, 15 to 86 years). The left ventricular ejection fraction was 41 ± 16% (range, 9% to 73%). Nine patients (20%) had prior myocardial infarction, and 27 patients (61%) had cardiomyopathy. When electrical storm developed, 24 of 44 patients (55%) had received antiarrhythmic drugs, including 6 patients (14%) had received oral amiodarone at a dose of 142 ± 61

Discussion

In this study, we demonstrated that the stepwise therapy of nifekalant and mexiletine was highly effective in the suppression of electrical storm. Furthermore, the stepwise therapy was also effective in patients who had electrical storm despite oral amiodarone therapy and in those who had recurrence of electrical storm during follow-up.

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Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease
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Citation Excerpt :
Such selectivity provides additional safety margin for using mexiletine in the management of LQTS. Moreover, mexiletine is reported that can help suppress electrical storms [31]. Under the canine left ventricular arterially perfused wedge preparations, with APDs simultaneously recorded from epicardial (Epi) and M cells together with a transmural ECG obtained, a longer APD was observed in M cells, compared to Epi cells, due to its larger INa-L densities than that in Epi cells at both recording sites in the experimental model of LQT3 with sea anemone toxin II (ATX-II, 20 nM), a specific enhancer of INa-L [27].
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^☆: Disclosures: None declared.

View full text

The effects of pure potassium channel blocker nifekalant and sodium channel blocker mexiletine on malignant ventricular tachyarrhythmias☆

Highlights

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

J Am Coll Cardiol

Ann Thorac Surg

Am Heart J

J Am Coll Cardiol

Heart Rhythm

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Treating electrical storm: sympathetic blockade versus advanced cardiac life support-guided therapy

Circulation

Electrical storm in patients with an implantable defibrillator: incidence, features, and preventive therapy: insights from a randomized trial

Eur Heart J

Electrical storm presages nonsudden death: the antiarrhythmics versus implantable defibrillators (AVID) trial

Circulation

Circulation

Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC study: a randomized trial

JAMA

A new class III antiarrhythmic drug, MS-551, blocks the inward rectifier potassium channel in isolated guinea pig ventricular myocytes

J Pharmacol Exp Ther