Should lethal arrhythmias in hypertrophic cardiomyopathy be predicted using non-electrophysiological methods?

While sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is due to arrhythmias, the guidelines for prediction of SCD are based solely on non-electrophysiological methods. This study aims to stimulate thinking about whether the interests of patients with HCM are better served by using current, 'risk factor', methods of prediction or by further development of electrophysiological methods to determine arrhythmic risk. Five published predictive studies of SCD in HCM, which contain sufficient data to permit analysis, were analysed to compute receiver operating characteristics together with their confidence bounds to compare their formal prediction either by bootstrapping or Monte Carlo analysis.

An extended computational model of the circulatory system for designing ventricular assist devices.

An extended computational model of the circulatory system has been developed to predict blood flow in the presence of ventricular assist devices (VADs). A novel VAD, placed in the descending aorta, intended to offload the left ventricle (LV) and augment renal perfusion is being studied. For this application, a better understanding of the global hemodynamic response of the VAD, in essence an electrically driven pump, and the cardiovascular system is necessary.

Paroxysmal atrial fibrillation is associated with increased intra-atrial conduction delay.

Aims: A novel electrophysiological technique, paced electrogram fractionation analysis (PEFA), which measures activation delay of stimulated beats through the myocardium, has shown that long delays in activation are strongly associated with sudden cardiac death due to ventricular fibrillation. The aim of our study was to determine whether there are differences in intra-atrial conduction in patients with and without paroxysmal atrial fibrillation (PAF) using PEFA. Twenty patients (15 women) in the mean age 54.

Paced ventricular electrogram fractionation predicts sudden cardiac death in hypertrophic cardiomyopathy.

Aims: Paced electrogram fractionation analysis (PEFA) has been assessed for the prediction of sudden cardiac death (SCD) in a large-scale, prospective study of patients with hypertrophic cardiomyopathy (HCM).

Methods And Results: We determined the positive predictive value (PPV) of PEFA in relation to other risk factors for SCD and outcomes in 179 patients with HCM and no prior history of cardiac arrest. Patients were followed over a mean 4.

Delayed paced ventricular activation in the long QT syndrome is associated with ventricular fibrillation.

Background: LQTS may cause sudden cardiac death (SCD), but the mechanisms linking gene mutations to ventricular fibrillation (VF) are unclear.

Objective: To determine whether ventricular activation delays in congenital long QT syndrome (LQTS) are associated with VF and to describe these delays clinically by measuring activation through ventricular myocardium after a premature extrastimulus.

Methods: Forty-six patients with LQTS, including 16 with VF (LQTS VF) were investigated, and the results were compared with those from 24 patients with hypertrophic cardiomyopathy and VF (HCM VF).

Numerical simulation of paced electrogram fractionation: relating clinical observations to changes in fibrosis and action potential duration.

Unlabelled: Simulating paced electrogram fractionation.

Introduction: Paced electrogram fractionation analysis (PEFA) may identify a re-entrant substrate in patients at risk of ventricular fibrillation (VF) by detecting prolonged, fractionated ventricular electrograms ("fractionation") in response to premature extrastimuli. Numerical simulations of action potential (AP) propagation through human myocardium following such premature stimulation were performed to study the relationship between electrogram fractionation, fibrosis, and changes in AP currents.

Electrogram prolongation and nifedipine-suppressible ventricular arrhythmias in mice following targeted disruption of KCNE1.

Mutations in KCNE1, the gene encoding the beta subunit of the slowly activating delayed rectifier potassium current (IKs) channel protein, may lead to the long QT syndrome (LQTS), a condition associated with enhanced arrhythmogenesis. Mice with homozygous deletion of the coding sequence of KCNE1 have inner ear defects strikingly similar to those seen in the corresponding human condition. The present study demonstrated and assessed the mechanism of ventricular arrhythmias in Langendorff-perfused whole heart preparations from homozygous KCNE1-/- mice compared to wild-type mice of the same age.

Sudden death in noncoronary heart disease is associated with delayed paced ventricular activation.

Background: Slowed or delayed myocardial activation and dispersed refractoriness predispose to reentrant excitation that may lead to ventricular fibrillation (VF). Increased ventricular electrogram duration (DeltaED) in response to extrastimuli and increased S1S2 coupling intervals at which electrogram duration starts to increase (S1S2delay) are seen both in hypertrophic cardiomyopathy (HCM) in those at risk of VF and in patients with idiopathic VF (IVF).

Methods And Results: DeltaED and S1S2delay have been measured using paced electrogram fractionation analysis in 266 patients with noncoronary heart disease.

Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a.

Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved.