Genetic aspects of arrhythmias

Roberts, Robert; Brugada, Ramón

doi:10.1002/1096-8628(200024)97:4<310::aid-ajmg1282>3.0.co;2-7

Cited by 21 publications

(13 citation statements)

References 72 publications

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“…Thus, an obvious focus would be defects in electrogenic protein coding genes implicated in the rare inherited syndromes, such as LQTS, including the ion channel genes (see section The Rare Disease Paradigm). Cytoskeleton proteins, such as ankyrin (recently associated with LQT4 52 ), and mutations in genes coding for structural proteins, such as those linked to SCDs in familial hypertrophic cardiomyopathies, [53][54][55][56][57][58][59][60] and in ARVC and catecholaminergic polymorphic ventricular tachycardia (CPVT) are also of interest. 18 Obviously, many other genes are involved in modulating cardiac excitability and conduction in different disease states and phenotypes, eg, matrix metalloproteinases (MMPs) with an important role in fibrosis, as well as processes such as inflammation, cell-tocell communication, and electrical and structural remodeling.…”

Section: Identifying New Scd Candidate Genesmentioning

confidence: 99%

Genomics in Sudden Cardiac Death

Arking

Chugh

Chakravarti

et al. 2004

Circulation Research

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Abstract-Sudden cardiac death (SCD) remains a public health problem of major magnitude. Contrary to earlier expectations, and despite decreased overall cardiac mortality, SCD rates appear to be rising in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. With the exception of the implantable defibrillator, there are few effective approaches to SCD prevention and even fewer clues concerning patient phenotypes predisposed to life-threatening arrhythmias. Clinical variables such as ejection fraction predict mortality but are not sensitive enough to identify many high SCD risk patients. The predictive power of autonomic dysregulation and markers such as lipid levels, hypertension, diabetes, and smoking is quite low in subclinical heart disease, the population in which the majority of SCDs occur. This review addresses advances in genomic science applicable to the SCD public health problem in both rare and common forms of heart disease. These include novel bioinformatic approaches to both identify candidate genes/pathways and identify previously unknown functional genetic elements, as well as methods to comprehensively screen these elements. We also discuss the possibility of applying high-density genome-wide SNP analyses to examine genetic contributions to arrhythmia susceptibility in community-based, case-control studies of common forms of SCD. The development of novel strategies to identify contributors to susceptibility in common cardiac phenotypes is most likely to lead to new and relevant therapeutic targets for SCD.

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Section: Identifying New Scd Candidate Genesmentioning

confidence: 99%

Genomics in Sudden Cardiac Death

Arking

Chugh

Chakravarti

et al. 2004

Circulation Research

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“…Song et al report that pretreatment with atorvastatin significantly reduced the occurrence of AF following OPCABG, 11 but as their study was not a double-blind and placebo-controlled trial, definitive conclusions cannot be drawn. In addition, AF has significant genetic heterogeneity, 12 and the effects of statins have ethnic differences, 13 so it is necessary to evaluate the effects of statins on postoperative AF in domestic patients undergoing OPCABG.…”

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confidence: 99%

Effect of Preoperative Atorvastatin Therapy on Atrial Fibrillation Following Off-Pump Coronary Artery Bypass Grafting

Mei

Wang

et al. 2009

Circ J

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“…Although several additional mutations in the same gene have been described afterward, these defects were identified in only a minority of patients reported in the literature. 4,5 Clinical observations indicate an involvement of the cardiac autonomic nervous system in the onset of ventricular tachyarrhythmias in patients with Brugada syndrome in whom ventricular tachycardia, syncope, and/or cardiac arrest occur more frequently during rest or sleep, when the vagal tone is predominant. 6 Furthermore, the magnitude of STsegment elevation can be reduced by adrenergic agonists, whereas it is increased by parasympathetic agonists or adrenergic antagonists.…”

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confidence: 99%

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

et al. 2004

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Background— Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. Methods and Results— Nine patients with Brugada syndrome (6 male, 3 female; age, 41±13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11 C-Hydroxyephedrine ( 11 C-HED) and the nonselective β-blocker 11 C-CGP 12177 ( 11 C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11 C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9±16.2 mL/g versus 69.1±14.2 mL/g; P <0.05), whereas postsynaptic β-adrenoceptor density, assessed by 11 C-CGP, was similar in patients and control subjects (10.4±6.7 pmol/g versus 10.2±2.9 pmol/g; P =NS). Conclusions— The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved β-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

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Genetic aspects of arrhythmias

Cited by 21 publications

References 72 publications

Genomics in Sudden Cardiac Death

Genomics in Sudden Cardiac Death

Effect of Preoperative Atorvastatin Therapy on Atrial Fibrillation Following Off-Pump Coronary Artery Bypass Grafting

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

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