Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator.

Local impedance-guided ablation and ultra-high density mapping versus conventional or contact force-guided ablation with mapping for treatment of cavotricuspid isthmus dependent atrial flutter.

Introduction: - Local impedance (LI) guided ablation as a method of judging lesion effectiveness for cavotricuspid isthmus dependent atrial flutter (CTI-AFL), and ultra-high density (UHD) mapping when breakthrough occurred across an ablation line has not previously been assessed.

Methods: This retrospective observational study evaluated patients undergoing CTI-AFL ablation using conventional, contact force (CF) and LI guided strategies. Ablation metrics were collected, and in the LI cohort, the use of UHD mapping for breakthrough evaluated.

Does rhythm matter in acute heart failure? An insight from the British Society for Heart Failure National Audit.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with acute heart failure (AHF). The presence of AF is associated with adverse prognosis in patients with chronic heart failure (CHF) but little is known about its impact in AHF.

Methods: Data were collected between April 2007 and March 2013 across 185 (> 95%) hospitals in England and Wales from patients with a primary death or a discharge diagnosis of AHF.

Mechanistic insight into spontaneous transition from cellular alternans to arrhythmia-A simulation study.

Cardiac electrical alternans (CEA), manifested as T-wave alternans in ECG, is a clinical biomarker for predicting cardiac arrhythmias and sudden death. However, the mechanism underlying the spontaneous transition from CEA to arrhythmias remains incompletely elucidated. In this study, multiscale rabbit ventricular models were used to study the transition and a potential role of INa in perpetuating such a transition.

Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide-gated and ryanodine 2 channels.

Background: Aging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction.

Objective: The aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging.

Methods: Electrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed.

Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics - Insights from a 3D Model of the Human Atria.

Aims: Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics.

Effective cascade screening through identification of a mutation in in a large family with a history of sudden death.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder which usually presents in the first or second decade of life with syncope, which is typically induced by emotional stress or exercise. We describe a large family with a history of three sudden unexpected deaths. Investigations in the sibling of a deceased individual affected by emotion-induced syncope revealed ventricular bigeminy.

Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model.

Background: Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear.

Objective: The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change.

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling.

Advantages of a subcutaneous implantable cardioverter-defibrillator in LAMP2 hypertrophic cardiomyopathy.

Danon disease is a rare X-linked lysosomal disease causing severe hypertrophic cardiomyopathy (LAMP2 cardiomyopathy) and an extremely poor prognosis in males, with several reported cases of sudden cardiac death despite the use of transvenous implantable cardioverter defibrillators (TV-ICD). We describe a case in which a TV-ICD was unable to defibrillate induced ventricular fibrillation (VF), but a wholly subcutaneous system (S-ICD) was successful in terminating induced VF and spontaneous ventricular tachycardia. These findings have relevance to the selection of device therapy in the management of these individuals and a wider group of young patients with severe hypertrophic cardiomyopathy.

Comparison of Atrial Fibrillation in the Young versus That in the Elderly: A Review.

The incidence and prevalence of atrial fibrillation (AF) are projected to increase significantly worldwide, imposing a significant burden on healthcare resources. The disease itself is extremely heterogeneous in its epidemiology, pathophysiology, and treatment options based on individual patient characteristics. Whilst ageing is well recognised to be an independent risk factor for the development of AF, this condition also affects the young in whom the condition is frequently symptomatic and troublesome.

The Year in Cardiology 2012: arrhythmia and pacing.

This is a commissioned review for 'A Year in Cardiology 2012', focusing on recent developments in the field of arrhythmias and pacing.

The clinical management of relatives of young sudden unexplained death victims; implantable defibrillators are rarely indicated.

Objective: Following national guidance on management of sudden unexplained death (SUD) in the young, inherited cardiac conditions (ICC) clinics were established to identify and treat relatives thought to be at increased risk. Studies have examined diagnostic yield of these clinics but outcome of clinical management has not been reported.

Design: Observational outcome study of consecutively referred relatives of SUD victims.

Virtual tissue engineering of the human atrium: modelling pharmacological actions on atrial arrhythmogenesis.

Computational models of human atrial cells, tissues and atria have been developed. Cell models, for atrial wall, crista terminalis, appendage, Bachmann's bundle and pectinate myocytes are characterised by action potentials, ionic currents and action potential duration (APD) restitution. The principal effect of the ion channel remodelling of persistent atrial fibrillation (AF), and a mutation producing familial AF, was APD shortening at all rates.

Ventricular fibrillation following successful DC cardioversion for atrial fibrillation.

Cardioversion remains an important therapy in the management of atrial fibrillation. Here, we report a case where direct current cardioversion resulted in a sudden dramatic change of heart rate that was associated with multiple ventricular fibrillation arrests in a manner akin to that previously observed post-atrioventricular node ablation.

Mycobacterium tuberculosis causing infection of an implantable biventricular defibrillator.

Mycobacterial infection of implantable cardiac devices is rare, and infection of pacing system components with M. tuberculosis has been reported on only three previous occasions, involving epicardial pacing systems in two cases. We report here a pocket infection with M.

Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes.

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death.

Effects of angiotensin receptor blockade on atrial electrical remodelling and the 'second factor' in a goat burst-paced model of atrial fibrillation.

Atrial fibrillation (AF) is self-perpetuating, via mechanisms of acute electrical remodelling and 'second factors' acting over a longer time course. Renin-angiotensin system (RAS) blockade may inhibit AF self-perpetuation. We evaluated the effects of RAS blockade with candesartan in a burst-paced goat model of lone AF in which both mechanisms are known to operate.