Early Afterdepolarization Abolished by Potassium Channel Opener in a Patient with Idiopathic Long QT Syndrome

Sato, Tetsuya; Hata, Yoshiki; Yamamoto, Mika; Morita, Hiroshi; Mizuo, Kozo; Yamanari, Hiroshi; Saito, Daiji; Ohe, Tohru

doi:10.1111/j.1540-8167.1995.tb00400.x

Cited by 61 publications

(20 citation statements)

References 10 publications

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“…In an acute study involving six patients, nicorandil abolished the repolarization abnormalities provoked by epinephrine [23], whereas normalization of monophasic action potential and abolition of T-wave alternans have been reported in isolated cases [36][37][38]. It should be emphasized, however, that all the studies of genotype-specific therapy share three important limitations: 1) these studies included very small numbers of patients (Table 1), 2) the follow-up periods were short, and 3) except for isolated reports [35,38], the effects on spontaneous arrhythmia suppression were not documented. The last limitation is especially important because the tendency to develop sustained arrhythmias varies tremendously among different patients with the same mutation and at different times in the same patient.…”

Section: Genotype-specific Drug Therapymentioning

confidence: 95%

“…Finally, the inadequate potassium outflow that is responsible for the repolarization abnormalities in patients with mutant I Ks channels (LQT1 genotype) was targeted with nicorandil, a potassium channel opener [23]. In an acute study involving six patients, nicorandil abolished the repolarization abnormalities provoked by epinephrine [23], whereas normalization of monophasic action potential and abolition of T-wave alternans have been reported in isolated cases [36][37][38]. It should be emphasized, however, that all the studies of genotype-specific therapy share three important limitations: 1) these studies included very small numbers of patients (Table 1), 2) the follow-up periods were short, and 3) except for isolated reports [35,38], the effects on spontaneous arrhythmia suppression were not documented.…”

Section: Genotype-specific Drug Therapymentioning

confidence: 99%

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Prevention of ventricular arrhythmias in the congenital long QT syndrome

Viskin

Fish

2000

Curr Cardiol Rep

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Life-long therapy is necessary for patients with symptomatic long QT syndrome to prevent arrhythmic death. The merits and limitations of the different therapeutic modalities are discussed. beta-blockers remain the mainstay of therapy, but this medication may not be sufficient for cardiac arrest survivors and for those with the LQT3 genotype. "Genotype-specific" therapy, like potassium-channel openers for patients with inadequate potassium outflow (LQT1 and LQT2 genotypes) or sodium-channel blockers for patients with excessive sodium inflow (LQT3), significantly shortens the QT interval, but the effects of these drugs on arrhythmia prevention is less well established. Cardiac pacemakers may be especially beneficial for patients with LQT2 or LQT3 and for those with pause-dependent torsade de pointes. More important is to recognize that device programming for preventing tachyarrhythmias in patients with long QT differs from the standard pacemaker programming. Finally, implantable defibrillators with dual-chamber pacing capability are indicated for patients at high risk for arrhythmic death, including all cardiac arrest survivors.

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Section: Genotype-specific Drug Therapymentioning

confidence: 95%

Section: Genotype-specific Drug Therapymentioning

confidence: 99%

Prevention of ventricular arrhythmias in the congenital long QT syndrome

Viskin

Fish

2000

Curr Cardiol Rep

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“…Intravenous administration of nicorandil counteracted the action potential prolongation induced by adrenaline in LQT1 patients [152]. It also led to the disappearance of the abnormal 'humps' on monophasic action potential downslope, which are believed to correspond to EADs [153,154]. No reliable data on clinical outcomes with nicorandil are available at this moment.…”

Section: Potential Future Treatmentmentioning

confidence: 99%

Congenital long QT syndromes and Brugada syndrome: the arrhythmogenic ion channel disorders

Němec

Shen

2001

Expert Opinion on Pharmacotherapy

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Congenital long QT syndromes (LQTS) and Brugada syndrome are hereditary disorders of cardiac ion channels which result in life-threatening cardiac arrhythmias or sudden cardiac death in patients with anatomically normal hearts. The pathogenesis of these dramatic events has been partially elucidated with the identification of the individual ion channels involved and understanding of the effect of some disease-causing mutations on the membrane currents and action potential. The clinical spectrum of congenital LQTS is broader than previously thought and involves certain patients previously diagnosed with idiosyncratic drug-induced proarrhythmia. The initial treatment for congenital LQTS patients involves beta-blockers in most cases. Indications for implantable cardioverter-defibrillator (ICD) or pace-maker (PM) implantation in selected individuals continue to evolve.

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“…Pharmacological activators of K ATP have been shown to protect against arrhythmias induced by triggered activity, EADs and DADs [264][265][266]. The K ATP opener nicorandil reduced EADs, shortened monophasic action potential duration and prevented syncope recurrence in patients with congenital LQT and in animal models of LQT [267][268][269]. Pharmacological activation of K ATP can reduce calcium overload and improve contractile function [270], and at least in part, this protective mechanism involves resting membrane potential hyperpolarization and reduction in reverse-mode NCX activity [271][272].…”

Section: Potassium Channel Activatorsmentioning

confidence: 99%

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

Baczkó

Leprán

Kiss

et al. 2014

CPD

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Heart failure (HF) is a clinical syndrome characterized by significant impairment of cardiac ventricular function. Atrial fibrillation (AF) is the most commonly observed sustained arrhythmia in clinical practice. Both HF and AF are associated with increased morbidity and mortality and their prevalence increases with age. Approximately 50% of patients with moderate HF die due to ventricular fibrillation that leads to sudden cardiac death. Patients with AF exhibit increased mortality due to HF and stroke. HF and AF often co-exist, and the development of the other condition further deteriorates prognosis. Both chronic HF and AF lead to structural and electrophysiological changes in the heart called remodeling, modifying therapeutic targets including those for antiarrhythmic intervention. Current pharmacological treatment of arrhythmias has major limitations due to low efficacy and serious adverse effects. In this review, the main aspects of electrical remodeling in HF and AF are discussed along with possible novel targets identified for future pharmacological antiarrhythmic therapy.Keywords: Heart failure, atrial fibrillation, cardiac arrhythmias, electrical remodeling, potassium channel expression, multi-channel blocking drugs. I. OVERVIEW AND CURRENT STATUS Epidemiology of Heart Failure, Atrial Fibrillation and their CombinationHeart failure (HF) is a clinical syndrome resulting from a wide range of cardiovascular disorders, featuring significant impairment of cardiac function that leads to reduced ventricular filling or ejection of blood. HF markedly reduces health-related quality of life [1], causes significant morbidity and high mortality and represents an enormous economic burden for the health care system [2]. The incidence of HF is increasing with age, with 20 per 1000 persons 65-69 years old and more than 80 per 1000 persons older than 85 [3] and its prevalence is increasing in a continuously aging population [2]. In spite of the significant advances in the treatment of HF, mortality rates remain poor at approximately 50% of patients dying within 5 years of diagnosis [4]. Serious ventricular arrhythmias are common in HF [5] and approximately 50% of HF patients die due to ventricular fibrillation leading to sudden cardiac death (SCD), the rate of which is several times higher in HF patients compared to the general population [6]. In addition to severe ventricular arrhythmias, atrial arrhythmias often develop in heart failure. Bradycardia can develop due to sinoatrial function impairment [7] that can exacerbate cardiac dysfunction [8], can lead to syncope and haemodynamic collapse and can be resolved by application of implantable devices [9].Atrial fibrillation (AF) is the most common sustained arrhythmia and it is associated with significant morbidity and mortality, especially due to the increased risk of heart failure and stroke [10][11][12]. The prevalence of AF increases with age, with 0.5% of patients affected in the 50 year old range, ~10% over the age of 80 [13] and the prediction is that it...

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Early Afterdepolarization Abolished by Potassium Channel Opener in a Patient with Idiopathic Long QT Syndrome

Cited by 61 publications

References 10 publications

Prevention of ventricular arrhythmias in the congenital long QT syndrome

Prevention of ventricular arrhythmias in the congenital long QT syndrome

Congenital long QT syndromes and Brugada syndrome: the arrhythmogenic ion channel disorders

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

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