Defibrillator Versus β-Blockers for Unexplained Death in Thailand (DEBUT)

Nademanee, Koonlawee; Veerakul, Gumpanart; Mower, Morton M.; Likittanasombat, Khanchit; Krittayapong, Rungroj; Bhuripanyo, K; Sitthisook, Surapun; Chaothawee, Lertlak; Lai, May C.; Azen, Stanley P.

doi:10.1161/01.cir.0000066319.56234.c8

Cited by 133 publications

(58 citation statements)

References 20 publications

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“…It is believed that BrS is an inherited disease attributed to genetic penetrance in family members. Currently, implantable cardioverter defibrillator (ICD) is the standard treatment for secondary prevention post‐SCA or syncope of unknown origin 5, 6. The ICD is an effective treatment to prevent cardiac arrest from recurrent ventricular tachycardia or ventricular fibrillation (VF) in BrS patients.…”

Section: Introductionmentioning

confidence: 99%

SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

Makarawate

Chaosuwannakit

Vannaprasaht

et al. 2017

JAHA

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BackgroundBrugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. SCN5A, encoding the α‐subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator (ICD) is the standard treatment for secondary prevention. This study aimed to evaluate association of the SCN5A variant with this cardiac conduction disturbance and appropriate ICD shock therapy in Thai symptomatic BrS patients with ICD implants.Methods and ResultsSymptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate ICD shock defined as having non‐pacing‐associated ICD shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between SCN5A polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate ICD shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with ICD implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate ICD shock therapy after ICD treatment. An independent factor associated with appropriate ICD shock therapy was SCN5A‐R1193Q with an adjusted hazard ratio of 10.550 (95% CI, 1.631–68.232).Conclusions SCN5A‐R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate ICD shock therapy in symptomatic BrS patients with ICD treatment. Because of the small sample size of study population and the appropriate ICD shock outcome, further large studies are needed to confirm the results of this study.

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Section: Introductionmentioning

confidence: 99%

SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

Makarawate

Chaosuwannakit

Vannaprasaht

et al. 2017

JAHA

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“…The only proven effective treatment of BrS is prophylactic implantation of an automatic cardioverter-defibrillator (ICD) unit [Brugada et al, 2000a;Nademanee et al, 2003]. However, a recent study has shown that during a follow-up of 43 years, only 2.6% of a cohort of BrS patients received appropriate shocks, whereas 8.9% experienced device-related complications .…”

Section: Introductionmentioning

confidence: 99%

The genetic basis of Brugada syndrome: A mutation update

et al. 2009

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Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the a-subunit of the Na v 1.5 sodium ion channel conducting the depolarizing I Na current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the a-subunit of the Ca v 1.2 ion channel conducting the depolarizing I L,Ca current; CACNB2, which encodes the stimulating b2-subunit of the Ca v 1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes b-subunits of the Na v 1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory b-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I to current. BrS exhibits variable expressivity, reduced penetrance, and ''mixed phenotypes,'' where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.

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“…Beta Blockers in Unexpected Death in Thailand (DEBUT) trial, 86 patients who survived cardiac arrest or had a Brugada type electrocardiogram were randomized to beta blockers or prophylactic ICD implant. 23 After 3-year follow-up, there were four deaths that all occurred in the beta-blocker arm. There were seven patients in the ICD arm who had appropriately treated VF.…”

Section: Indicationsmentioning

confidence: 99%

Implantable cardiac arrhythmia devices—Part II: Implantable cardioverter defibrillators and implantable loop recorders

Kusumoto

Goldschlager

2006

Clinical Cardiology

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Summary: Implantable cardiac devices have become firmly entrenched as important therapeutic tools for a variety of cardiac conditions. The second part of this two-part review discusses the contemporary use and follow-up of implantable cardioverter defibrillators (ICD) and the implantable loop recorder. The ICD has become the standard therapy for protecting patients against sudden cardiac death. Two recent trials, the Multicenter Automatic Defibrillator Trial II (MADIT II) and the Sudden Cardiac Death Heart Failure Trial (SCD-HEFT), demonstrated that the ICD is associated with a significant survival benefit for patients with reduced ejection fraction (< 0.30-0.35), particularly if heart failure symptoms are present. The ICD has an important role in the management of other conditions associated with a high risk for sudden death, such as hypertrophic cardiomyopathy, long QT syndrome, and Brugada syndrome. The implantable loop recorder has become an important diagnostic tool for the patient with unexplained syncope.

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Defibrillator Versus β-Blockers for Unexplained Death in Thailand (DEBUT)

Cited by 133 publications

References 20 publications

SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome

The genetic basis of Brugada syndrome: A mutation update

Implantable cardiac arrhythmia devices—Part II: Implantable cardioverter defibrillators and implantable loop recorders

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