Sudden cardiac death due to ventricular tachycardia (VT) is a major health issue worldwide. Efforts to identify patients at risk, determine VT mechanisms, and effectively prevent and treat VT with a mechanism-based approach would benefit from continuous noninvasive imaging of the arrhythmia over the entire heart. This paper presents the first noninvasive images of human ventricular arrhythmias using electrocardiographic imaging (ECGI), highlighting the large diversity of human VT in terms of activation patterns, mechanisms, and sites of initiation. Based on comparison with catheter mapping, ECGI provided high spatial resolution; a property that overcomes a limitation of the body surface electrocardiogram, which provides only global information. The spatial resolution and ability to image the activation sequences over the entire ventricular surfaces in a single beat allowed us to make observations regarding VT initiation and continuation, and regarding relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. The ability of ECGI to provide patient-specific physiologic insights, to map the VT activation sequence and to identify the location and depth of VT origin from a single beat has important clinical implications in treating patients with ventricular arrhythmias.

Objective To compare the long term efficacy and adverse events of dual blockade of the renin-angiotensin system with monotherapy.Design Systematic review and meta-analysis.Data sources PubMed, Embase, and the Cochrane central register of controlled trials, January 1990 to August 2012.Study selection Randomised controlled trials comparing dual blockers of the renin-angiotensin system with monotherapy, reporting data on either long term efficacy (≥1 year) or safety events (≥4 weeks), and with a sample size of at least 50. Analysis was stratified by trials with patients with heart failure versus patients without heart failure.Results 33 randomised controlled trials with 68 405 patients (mean age 61 years, 71% men) and mean duration of 52 weeks were included. Dual blockade of the renin-angiotensin system was not associated with any significant benefit for all cause mortality (relative risk 0.97, 95% confidence interval 0.89 to 1.06) and cardiovascular mortality (0.96, 0.88 to 1.05) compared with monotherapy. Compared with monotherapy, dual therapy was associated with an 18% reduction in admissions to hospital for heart failure (0.82, 0.74 to 0.92). However, compared with monotherapy, dual therapy was associated with a 55% increase in the risk of hyperkalaemia (P<0.001), a 66% increase in the risk of hypotension (P<0.001), a 41% increase in the risk of renal failure (P=0.01), and a 27% increase in the risk of withdrawal owing to adverse events (P<0.001). Efficacy and safety results were consistent in cohorts with and without heart failure when dual therapy was compared with monotherapy except for all cause mortality, which was higher in the cohort without heart failure (P=0.04 v P=0.15), and renal failure was significantly higher in the cohort with heart failure (P<0.001 v P=0.79).Conclusion Although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events such as hyperkalaemia, hypotension, and renal failure compared with monotherapy. The risk to benefit ratio argues against the use of dual therapy.

Objectives To noninvasively image the electophysiologic substrate of human ventricles after myocardial infarction and define its characteristics. Background Ventricular infarct border zone is characterized by abnormal cellular electrophsyiology and altered structural architecture and is a key contributor to arrhythmogenesis. The ability to noninvasively image its electrical characteristics could contribute to understanding of mechanisms and to risk-stratification for ventricular arrhythmia. Methods Electrocardiographic Imaging (ECGI), a noninvasive functional electrophysiologic imaging modality, was performed during sinus rhythm in 24 subjects with infarct-related myocardial scar. The abnormal electrophysiologic substrate on the epicardial aspect of the scar was identified and its location, size, and morphology were compared to the anatomic scar imaged by other noninvasive modalities. Results ECGI constructs epicardial electrograms which have characteristics of reduced amplitude (low voltage) and fractionation. ECGI co-localizes the epicardial electrical scar to the anatomic scar with a high degree of accuracy (sensitivity 89%, specificity 85%). In nearly all subjects, sinus rhythm activation patterns were affected by the presence of myocardial scar. Late potentials could be identified and were almost always within ventricular scar. Conclusions ECGI accurately identifies areas of anatomic scar and complements standard anatomic imaging by providing scar - related electrophysiologic characteristics of low voltages, altered sinus rhythm activation, electrogram fragmentation and presence of late potentials.

Background Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. While its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging (ECGI) to map the cardiac electrophysiologic substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate which promotes arrhythmogenesis. Methods and Results 25 subjects (9 LQT1, 9 LQT2, 5 LQT3 and 2 LQT5) with genotype and phenotype positive LQTS underwent ECGI. Seven normal subjects provided control. Epicardial maps of activation, recovery times (RT), Activation-recovery intervals (ARI) and repolarization dispersion were constructed. Activation was normal in all patients. However, RT and ARI were prolonged relative to control, indicating delayed repolarization and abnormally long APD (312 ± 30 ms vs. 235 ± 21 ms in control). ARI prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119 ± 19 ms/cm vs. 2.0 ± 2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130 ± 27 ms/cm in 12 symptomatic patients vs. 98 ± 19 ms/cm in 13 asymptomatic patients; P < 0.05). Conclusions LQTS patients display regions with steep repolarization dispersion caused by localized APD prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECGI in risk stratification.