Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

Shimizu, Wataru; Noda, Takashi; Takaki, Hiroshi; Kurita, Takashi; Nagaya, Noritoshi; Sato, Kazuhiro; Suyama, Kazuhiro; Aihara, Naohiko; Kamakura, Shiro; Sunagawa, Kenji; Echigo, Shigeyuki; Nakamura, Kazufumi; Ohe, Tohru; Towbin, Jeffrey A.; Napolitano, Carlo; Priori, Silvia G.

doi:10.1016/s0735-1097(02)02850-4

Cited by 189 publications

(134 citation statements)

References 21 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…Clinical studies by our group and others suggest that sympathetic stimulation with epinephrine infusion or exercise testing produces genotype-specific responses of the QT interval [33,[47][48][49][50][51][52]. The corrected QT (QTc) interval is prolonged at peak epinephrine effect when the heart rate is maximally increased, and remains prolonged at steady state epinephrine effect in LQT1 patients [48,52].…”

Section: Genotype-specific Response To Sympathetic Stimulationmentioning

confidence: 99%

Specific Therapy Based on the Genotype and Cellular Mechanism in Inherited Cardiac Arrhythmias. Long QT Syndrome and Brugada Syndrome

Shimizu

Aiba²,

Antzelevitch

2005

CPD

Self Cite

View full text Add to dashboard Cite

Seven forms of congenital long QT syndrome (LQTS) caused by mutations in ion channel genes have been identified. Genotype-phenotype correlation in clinical and experimental studies involving arterially-perfused canine left ventricular wedges suggest that ,β-blockers are protective in LQT1, less so in LQT2, but not protective in LQT3. A class IB sodium channel blocker, mexiletine, is most effective in abbreviating QT interval in LQT3, but effectively reduces transmural dispersion of repolarization (TDR) and prevents the development of Torsade de Pointes (TdP) in all 3 models, suggesting its potential as an adjunctive therapy in LQT1 and LQT2. High concentrations of intravenous nicorandil, a potassium channel opener, have been shown to be capable of decreasing QT and TDR, and preventing TdP in LQT1 and LQT2 but not in LQT3. The calcium channel blocker, verapamil, has also been suggested as adjunctive therapy for LQT1, LQT2 and possibly LQT3.Experimental data using right ventricular wedge preparations suggest that a prominent transient outward current (I to )-mediated action potential (AP) notch and a loss of AP dome in epicardium, but not in endocardium, give rise to a transmural voltage gradient, resulting in ST segment elevation and the induction of ventricular fibrillation (VF), characteristics of the Brugada syndrome. Since the maintenance of the AP dome is determined by the balance of currents active at the end of phase 1 of the AP, any intervention that reduces the outward current or boosts inward current at the end of phase I may normalize the ST segment elevation and suppress VF. Such interventions are candidates for pharmacological therapy of the Brugada syndrome. The infusion of isoproterenol, a β-adrenergic stimulant, strongly augments L-type calcium current (I Ca-L ), and is the first choice for suppressing electrical storms associated with Brugada syndrome. Quinidine, by virtue of its actions to block I to , has been proposed as adjunctive therapy, with an implantable cardioverter defibrillator as backup. Oral denopamine, atropine or cilostazol all increase I Ca-L , and for this reason may be effective in reducing episodes of VF.

show abstract

Section: Genotype-specific Response To Sympathetic Stimulationmentioning

confidence: 99%

Specific Therapy Based on the Genotype and Cellular Mechanism in Inherited Cardiac Arrhythmias. Long QT Syndrome and Brugada Syndrome

Shimizu

Aiba²,

Antzelevitch

2005

CPD

Self Cite

View full text Add to dashboard Cite

show abstract

“…Epinephrine challenge is considered a powerful provocative test in the unmasking of low-penetrance KCNQ1 mutation carriers. 51 A number of nonpharmacologic positional and other maneuvers affecting autonomic tone have also been studied, to a less rigorous degree, as possible inducers of the LQTS phenotype.…”

Section: Phenotypic Ascertainment: Other Diagnostic Testsmentioning

confidence: 99%

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Modell

Lehmann

2006

Genetics in Medicine

146

View full text Add to dashboard Cite

Long QT syndrome (LQTS) refers to a group of "channelopathies"-disorders that affect cardiac ion channels. The "family" concept of syndromes has been applied to the multiple LQTS genotypes, LQT1-8, which exhibit converging mechanisms leading to QT prolongation and slowed ventricular repolarization. The 470ϩ allelic mutations induce loss-of-function in the passage of mainly K ϩ ions, and gain-of-function in the passage of Na ϩ ions through their respective ion channels. Resultant early after depolarizations can lead to a polymorphic form of ventricular tachycardia known as torsade de pointes, resulting in syncope, sudden cardiac death, or near-death (i.e., cardiac arrest aborted either spontaneously or with external defibrillation). LQTS may be either congenital or acquired. The genetic epidemiology of both forms can vary with subpopulation depending on the allele, but as a whole, LQTS appears in every corner of the globe. Many polymorphisms, such as HERG P448R and A915V in Asians, and SCN5A

show abstract

“…The test was negative for LQTS according to current criteria. 13 After a washout period, we performed a flecainide challenge test giving 2 mg/kg in a continuous infusion for 10 min, 14 with a baseline ECG and further recordings every 2 min. This was negative for BS.…”

Section: Description Of the Index Casementioning

confidence: 99%

Novel SCN5A Mutation Associated with Idiopathic Ventricular Fibrillation Due to Subclinical Brugada Syndrome

et al. 2011

View full text Add to dashboard Cite

Idiopathic ventricular fibrillation can be caused by subclinical channelopathies such as Brugada syndrome. Our objective is to study the clinical behaviour of a new SCN5A mutation found in a woman with idiopathic ventricular fibrillation. A 53-year-old woman presented with multiple episodes of ventricular fibrillation, a structurally normal heart and normal baseline electrocardiogram. Genetic testing included KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 and identified a mutation in SCN5A (D1816fs/g98747-98748insT). We studied 15 immediate family members by means of electrocardiogram, echocardiogram, flecainide challenge test and genetic study. Eight subjects had the mutation. The flecainide challenge test was positive for Brugada syndrome in two subjects in the case group and none in the control group. The PR and QRS intervals on the baseline electrocardiogram were longer in the case group. The left atrial volume indexed to body surface was higher in the case group, likely due to the fact that two patients with the mutation had atrial fibrillation and none had it in the control group. The D1816fs/g98747-98748insT mutation in SCN5A may be associated with idiopathic ventricular fibrillation and Brugada syndrome with a broad phenotypic spectrum and incomplete penetrance. Genetic testing may be useful to identify the etiology of idiopathic ventricular fibrillation in patients with a negative thorough clinical evaluation.

show abstract

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

Abstract: Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

Cited by 189 publications

References 21 publications

Specific Therapy Based on the Genotype and Cellular Mechanism in Inherited Cardiac Arrhythmias. Long QT Syndrome and Brugada Syndrome

Specific Therapy Based on the Genotype and Cellular Mechanism in Inherited Cardiac Arrhythmias. Long QT Syndrome and Brugada Syndrome

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Novel SCN5A Mutation Associated with Idiopathic Ventricular Fibrillation Due to Subclinical Brugada Syndrome

Contact Info

Product

Resources

About