Use of therapeutic hypothermia and extracorporeal life support after an unusual response to the ajmaline challenge in a patient with Brugada syndrome

AbstractBackgroundBrugada syndrome is a cardiac disorder associated with a high risk of sudden cardiac death, especially in young subjects. The incidence and prevalence are likely underestimated. The diagnosis is based on a characteristic electrocardiography (ECG) pattern. The most commonly performed confirmatory test in cases of equivocal ECG is the intravenous ajmaline challenge. Although relatively safe, it carries the risk of ventricular arrhythmias that could potentially degenerate into a refractory electrical storm.Case reportA 27-year-old man developed sustained ventricular fibrillation after ajmaline challenge. He was rescued on extracorporeal life support after 108min of cardiopulmonary resuscitation. Extracorporeal life support allowed recovery of spontaneous circulation and resulted in a positive neurological outcome.<Learning objective: This case is an example of how extracorporeal life support was instituted after prolonged and unsuccessful cardiopulmonary resuscitation resulting in a positive central neurological outcome.

Brugada syndrome and p.E61X_RANGRF

Background: Brugada syndrome is an inherited cardiac condition transmitted with an autosomal dominant pattern which can lead to sudden cardiac death from malignant ventricular arrhythmias. The RANGRF gene has recently been proposed to be associated with Brugada syndrome. This gene encodes the MOG1 protein, a co-factor required for the full functioning of the cardiac sodium channel Nav1.5. The nonsense p.E61X genetic variation in the RANGRF gene has been postulated as responsible for Brugada syndrome although no clear association has been established. Methods: We clinically and genetically evaluated a Spanish family diagnosed with Brugada syndrome. A comprehensive genetic analysis of all genes to date responsible for Brugada syndrome was performed in the index case. Results: The index case was clinically diagnosed with Brugada syndrome after flecainide test. We identified a nonsense variation (p.E61X) in the index case and in other five family members. All of them showed a normal electrocardiogram in basal conditions. Flecainide test unmasked a type 1 Brugada syndrome electrocardiogram only in two of the relatives. Conclusions: We suggest that p.E61X_RANGRF is a rare genetic variation with an uncertain role in Brugada Syndrome. Further studies must be performed to elucidate the potential pathogenic role of p.E61X_RANGRF in Brugada Syndrome

Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms:results from a multicentre long-term registry

AIMS : To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION : Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Detection of a Brugada syndrome in a occupational medical examination

Artículos originales[ES] El síndrome de Brugada es una cardiopatía genética y no estructural debida a una alteración primaria de los canales iónicos del miocardio y que se asocia a un riesgo de muerte súbita. Hay tres patrones electrocadiográficos diagnósticos o sugerentes de síndrome de Brugada, que pueden ser identificados en un reconocimiento médico rutinario y que, de confirmarse el diagnóstico, pueden llevar a la necesidad de implantar un desfibrilador automático que puede salvar la vida del paciente. Se presente un caso asintomático diagnosticado en un reconocimiento laboral y se revisa la conducta a seguir ante un síndrome de Brugada. [EN] Brugada syndrome is a genetic, non-structural heart disease caused by a primary alteration of the myocardial ion channels and it is associated with increased risk of sudden death. There are three electrocardiographic patterns diagnostic or suggestive of Brugada syndrome which can be identified in routine medical examinations. If the diagnosis is confirmed, implantation of an automatic defibrillator may be life-saving. We report an asymptomatic case of Brugada syndrome diagnosed during an occupational health check and review the steps to be followed after diagnosis of this syndrome.[EN] Brugada syndrome is a genetic, non-structural heart disease caused by a primary alteration of the myocardial ion channels and it is associated with increased risk of sudden death. There are three electrocardiographic patterns diagnostic or suggestive of Brugada syndrome which can be identified in routine medical examinations. If the diagnosis is confirmed, implantation of an automatic defibrillator may be life-saving. We report an asymptomatic case of Brugada syndrome diagnosed during an occupational health check and review the steps to be followed after diagnosis of this syndrome.N

Prevalence of the RR genotypes of the locus ACTN3-R577X in Italian Muay Thai elite fighters

BACKGROUND: The α-actinin skeletal muscle isoform 3 ACTN3 p.Arg577X is one of the most frequently genetic variants tested for professional sports and exercise. The aim of this work was to evaluate the prevalence of the ACTN3 p.Arg577X genotypes in a consecutive series of 117 Italian Muay Thai elite fighters enrolled during the agonistic eligibility screening programs. METHODS: One hundred and seventeen professional Muay Thai Italian athletes and 150 controls (all coming from Sardinia) were genotyped for the ACTN3 polymorphisms (SNP ID rs1815739) using real-time polymerase chain reaction. RESULTS: In the two groups, the genotypes' distribution was as per the Hardy-Weinberg principle (P>0.05). Statistically significant differences were observed for the ACTN3 X-allele that was more frequent in the athletes group compared to the controls (32% vs. 29.2%; P=0.012). The association between the genotype (Arg and X alleles) and the athletic status for the participants were statistically different in the Muay Thai group (Arg/Arg 46.2%, Arg/X 43.5% and X/X 10.3%) compared with the controls (Arg/Arg 50%, Arg/X 41.3% and X/X 8.7%). Muay Thai is characterized is a highly demanding sport in terms of both anaerobic and aerobic exercise, due to the powerful strikes and intense resistance training programs. Our results shed light onto a much-debated issue regarding the contribution of genetics to physical performance in the setting of martial arts at elite level in Italy. Since both power and endurance-related phenotypes are needed to excel at elite level, it would be logical that the ArgX genotype played a key role in fighting performance. However, the prevalence of ArgArg+ArgX demonstrates that the R allele is still the "most desirable" genotype. CONCLUSIONS: Although the present study was carried out on a small cohort of professional fighters, it can be concluded that the ACTN3 Arg allele is the "favored genotype"