Initial Experience With Nifekalant Hydrochloride (MS-551), A Novel Class III Antiarrhythmic Agent, in Patients With Acute Extensive Infarction and Severe Ventricular Dysfunction

Abstract

It has the unique characteristic of potent, nonselective K + channel blocking without inhibiting either the Na + channels or the -adrenergic receptors. In canine models of myocardial infarction, NIF effectively suppressed ventricular tachyarrhythmia, without compromising hemodynamics. 2,3 We report our initial experience of using NIF in patients with acute extensive infarction and severe ventricular dysfunction.Four male patients (age, 67±10 [mean ± SD] years) were referred because of extensive anterior acute myocardial infarction (AMI). All patients had single-vessel disease (the proximal left anterior descending artery) for which percutaneous transluminal coronary angioplasty was performed. The peak level of creatine kinase was 8,102±5,552 U/L. Echocardiography revealed severely depressed left ventricular function with 16±4% fractional shortening. In 2 of 4 patients (cases 1 and 3), intra-aortic balloon pumping was introduced for circulatory support. The patients' characteristics are summarized in Table 1.Despite successful reperfusion therapy, ventricular tachyarrhythmia (sustained ventricular tachycardia or fibrillation) developed 48-72 h following the AMI. None of the patients responded to therapy with lidocaine and/or procainamide under the correction of electrolyte (potassium and magnesium) and acid -base disturbance. We decided to use NIF intravenously, infusing a loading dose of 0.05-0.15 mg/kg and a maintenance dose of 0.05-0.20 mg·kg -1 ·h -1 , which were much lower doses than those used in a previous study (loading dose: 0.30 mg/kg; maintenance dose: 0.60mg·kg -1 · h -1 ). 4 The ventricular tachyarrhythmia, which was refractory to class IA and IB drugs, was effectively suppressed by NIF; the corrected QT interval (QTC) was extended to 0.58±0.03, from 0.46±0.05 s of the baseline. During the NIF infusion, the hemodynamics did not appear to deteriorate; rather, they were stablized in conjuction with the controlling of the malignant ventricular tachyarrhythmia. None of the patients needed additional antiarrhythmic therapy when NIF was discontinued after 1-19 days. Fig 1 shows the ECG recordings from case 1, a 59-yearold man who was supported by intra-aortic balloon pumping. The drug-refractive ventricular tachyarrhythmia (Fig 1B) was successfully treated with NIF at a loading dose of 0.15 mg/kg and a maintenance dose of 0.1 mg·kg -1 ·h -1 , which extended the QTc to 0.51 s (Fig 1C). Neither the pulmonary capillary wedge pressure (from 19 to 16 mmHg) nor the cardiac index (from 1.9 to 1.9 L·min -1 ·m -2 ) changed significantly following NIF treatment. Fig 2 shows the ECG recordings from case 2, a 78-yearold man with a 24% left ventricular ejection fraction. His monomorphic sustained ventricular tachycardia (Fig 2B) was initially treated with NIF at a loading dose of 0.15 mg/kg and a maintenance dose of 0.1 mg·kg -1 ·h -1 . Although the original arrhythmia disappeared, torsade de pointes (Fig 2D) newly developed when the QTc exceeded 0.60 s (Fig 2C). After NIF was decreased to 0.05 mg · kg -1 · h -1 , the ...

Efficacy of Nifekalant Hydrochloride in the Treatment of Fatal Ventricular Arrhythmia in Patients With Ischemic Heart Disease

“…Takenaka, et al 19) reported that nifekalant is effective in treating malignant ventricular tachyarrhythmia following AMI with severe ventricular dysfunction that is refractory to class Ia and Ib antiarrhythmic agents. In another report, Igawa, et al showed that nifekalant could be an alternative drug for suppression of VT in patients with OMI.…”

“…This agent does, however, sometimes induce torsade de pointes 19) as a result of overdose. In our study, adverse events reported in association with nifekalant administration were marked QTc interval prolongation in two patients, one of whom experienced torsade de pointes.…”

Experience With Nifekalant Hydrochloride in a Patient With Ischemic Cardiomyopathy and Severe Ventricular Dysfunction After Dor Operation

“…Vol 45 No 4 In conclusion, intravenous infusion of NIF can be expected to be an effective, safe, and quick treatment for postoperative malignant VT refractory to class I agents with severe LV dysfunction under monitoring of QTc.…”

“…Therefore, NIF is particularly suited for treatment of VT in patients with severe LV dysfunction. 4) Class III agents increase cardiac refractory periods by lengthening the action potential duration (APD) and delaying recovery of excitability, and thus inhibit the re-entry circuit. But this prolongation of APD becomes less marked with an increase in heart rate.…”

Nifekalant Hydrochloride Suppresses Severe Electrical Storm in Patients With Malignant Ventricular Tachyarrhythmias

“…[12][13][14] In an experimental model of previous myocardial infarction nifekalant was effective against ventricular tachyarrhythmias, [15][16][17][18] and moreover, this effect was recently reported in patients with ischemic heart disease. [19][20][21][22][23] therefore, we investigated the efficacy and safety of nifekalant for the control of severe electrical storm in patients with an ICD.…”