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Aims There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. Methods and results We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097–0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639–2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). Conclusion The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. Trial registration Clinical Trials Registration: NCT02459574. [ABSTRACT FROM AUTHOR]

Loss of function mutations in store‐operated Ca2+ entry (SOCE) are associated with severe paediatric disorders in humans, including combined immunodeficiency, anaemia, thrombocytopenia, anhidrosis and muscle hypotonia. Given its central role in immune cell activation, SOCE has been a therapeutic target for autoimmune and inflammatory diseases. Treatment for such chronic diseases would require prolonged SOCE inhibition. It is, however, unclear whether chronic SOCE inhibition is viable therapeutically. Here we address this issue using a novel genetic mouse model (SOCE hypomorph) with deficient SOCE, nuclear factor of activated T cells activation, and T cell cytokine production. SOCE hypomorph mice develop and reproduce normally and do not display muscle weakness or overt anhidrosis. They do, however, develop cardiovascular complications, including hypertension and tachycardia, which we show are due to increased sympathetic autonomic nervous system activity and not cardiac or vascular smooth muscle autonomous defects. These results assert that chronic SOCE inhibition is viable therapeutically if the cardiovascular complications can be managed effectively clinically. They further establish the SOCE hypomorph line as a genetic model to define the therapeutic window of SOCE inhibition and dissect toxicities associated with chronic SOCE inhibition in a tissue‐specific fashion. Key points: A floxed stromal interaction molecule 1 (STIM1) hypomorph mouse model was generated with significant reduction in Ca2+ influx through store‐operated Ca2+ entry (SOCE), resulting in defective nuclear translocation of nuclear factor of activated T cells, cytokine production and inflammatory response. The hypomorph mice are viable and fertile, with no overt defects.Decreased SOCE in the hypomorph mice is due to poor translocation of the mutant STIM1 to endoplasmic reticulum–plasma membrane contact sites resulting in fewer STIM1 puncta.Hypomorph mice have similar susceptibility to controls to develop diabetes but exhibit tachycardia and hypertension. The hypertension is not due to increased vascular smooth muscle contractility or vascular remodelling.The tachycardia is not due to heart‐specific defects but rather seems to be due to increased circulating catecholamines in the hypomorph.Therefore, long term SOCE inhibition is viable if the cardiovascular defects can be managed clinically. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is a rare genetic disease, of which its clinical manifestations include, but not limited to, syncope or sudden cardiac death. A 30‑year‑old Bangladeshi male patient with a past medical history of epilepsy was admitted following successful resuscitation from an out of hospital cardiac arrest secondary to ventricular fibrillation. Electrocardiogram (ECG) upon admission was suggestive of BrS type I. His old medical record showed similar ECG 2 months earlier when he had presented with syncope and was diagnosed with seizure. The correlation between BrS and epilepsy has been reported in the literature, discussing whether seizure is an uncommon presentation of BrS or whether epilepsy and BrS share similar genetic mutations that have the potential to cause both arrhythmia and seizures in some patients. Patients who present with seizure and ECG suggestive of Brugada pattern should be evaluated to rule out associated or underlying cardiac arrhythmia. [ABSTRACT FROM AUTHOR]

In 1992, the Brugada brothers published a patient series of aborted sudden death, who were successfully resuscitated from ventricular fibrillation (VF). These patients had a characteristic coved ST‑segment elevation in the right precordial leads on their 12‑lead electrocardiogram with no apparent structural heart abnormality. This disease was referred to as "right bundle branch block, persistent ST‑segment elevation, and sudden death syndrome." The term Brugada syndrome (BrS) was first coined for this new arrhythmogenic entity in 1996. BrS is more prevalent in Southeast Asian ethnic groups and was considered a familial disease due to the presence of syncope and/or sudden deaths in several members of the same family, however, the genetic alteration was only noted in 1998. The genetic characterization of BrS has proven to be challenging. The most common and well‑established BrS genotype involves loss‑of‑function mutations in the SCN5A gene, but only represents between 15% and 30% of the diagnosed patients. Patients with BrS can present with a range of symptoms which can include syncope, seizures, and nocturnal agonal breathing due to polymorphic ventricular tachycardia or VF. If these arrhythmias are sustained, sudden cardiac death may result. Despite the significant progress on the understanding of BrS over the last two decades, there remain a number of uncertainties and challenges; we present an update review on the subject. [ABSTRACT FROM AUTHOR]