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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. It was shown CEA evolved into either concordant or discordant action potential (AP) conduction alternans in a homogeneous one-dimensional tissue model, depending on tissue AP duration and conduction velocity (CV) restitution properties. Discordant alternans was able to cause conduction failure in the model, which was promoted by impaired sodium channel with either a reduced or increased channel current. In a two-dimensional homogeneous tissue model, a combined effect of rate- and curvature-dependent CV broke-up alternating wavefronts at localised points, facilitating a spontaneous transition from CEA to re-entry. Tissue inhomogeneity or anisotropy further promoted break-up of re-entry, leading to multiple wavelets. Similar observations have also been seen in human atrial cellular and tissue models. In conclusion, our results identify a mechanism by which CEA spontaneously evolves into re-entry without a requirement for premature ventricular complexes or pre-existing tissue heterogeneities, and demonstrated the important pro-arrhythmic role of impaired sodium channel activity. These findings are model-independent and have potential human relevance.

A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3months after cardio version (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodelled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished.

A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3months after cardio version (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodelled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. METHODS AND RESULTS: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. CONCLUSIONS: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. METHODS AND RESULTS: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. CONCLUSIONS: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.

AIMS: Atrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta-analysis to study the effects of the presence of AF on mortality in CHF patients. METHODS AND RESULTS: A systematic MEDLINE search for all randomized trials and observational studies in which the influence of AF on CHF mortality was investigated and meta-analysis of the mortality data was performed. A total of 16 studies were identified of which 7 were randomized trials and 9 were observational studies including 30,248 and 23,721 patients, respectively. An adjusted meta-analysis of the data revealed that the presence of AF is associated with an adverse effect on total mortality with an odds ratio (OR) of 1.40 [95% confidence interval (CI) 1.32-1.48, P < 0.0001] in randomized trials and an OR of 1.14 (95% CI 1.03-1.26, P < 0.05) in observational studies. This increase in mortality associated with the presence of AF was observed in subgroups of CHF patients with both preserved and impaired left ventricular (LV) systolic function. CONCLUSION: In conclusion, meta-analysis of 16 studies involving 53,969 patients suggests that the presence of AF is associated with an adverse prognosis in CHF irrespective of LV systolic function.

AIMS: Atrial fibrillation (AF) is one of the commonest sustained arrhythmias in chronic heart failure (CHF), although the prognostic implications of the presence of AF in CHF remain controversial. We have therefore performed this meta-analysis to study the effects of the presence of AF on mortality in CHF patients. METHODS AND RESULTS: A systematic MEDLINE search for all randomized trials and observational studies in which the influence of AF on CHF mortality was investigated and meta-analysis of the mortality data was performed. A total of 16 studies were identified of which 7 were randomized trials and 9 were observational studies including 30,248 and 23,721 patients, respectively. An adjusted meta-analysis of the data revealed that the presence of AF is associated with an adverse effect on total mortality with an odds ratio (OR) of 1.40 [95% confidence interval (CI) 1.32-1.48, P < 0.0001] in randomized trials and an OR of 1.14 (95% CI 1.03-1.26, P < 0.05) in observational studies. This increase in mortality associated with the presence of AF was observed in subgroups of CHF patients with both preserved and impaired left ventricular (LV) systolic function. CONCLUSION: In conclusion, meta-analysis of 16 studies involving 53,969 patients suggests that the presence of AF is associated with an adverse prognosis in CHF irrespective of LV systolic function.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic heart failure (CHF). Under-detection of asymptomatic paroxysmal AF (PAF) underestimates the true burden of AF in patients with CHF. We retrospectively studied the prevalence of asymptomatic PAF in 162 CHF patients through analysis of cardiac resynchronization therapy (CRT) device downloads to determine whether these episodes are associated with adverse outcomes. METHODS AND RESULTS: An episode of AF was defined by mode switching on CRT devices with an atrial rate >200 for at least 30 s. Of the 101 patients thought to be persistently in sinus rhythm (SR), 27% were found to have significant paroxysms of AF, with the cumulative percentage of time in the 'mode-switch mode' (i.e. the AF burden) of 1.6 +/- 0.9%. Mortality was 19.2% in patients with newly identified PAF with hospitalization and thrombo-embolism rates of 42.3 and 2.1%, respectively, compared with mortality of 10.4% with hospitalization and thrombo-embolism rates of 41.8 and 1.9%, respectively, in patients persistently in SR (P= NS). CONCLUSION: Analysis of data from CRT devices in a population of CHF patients with severe left ventricular dysfunction shows that a significant proportion of those perceived to be persistently in SR have undiagnosed paroxysms of AF but with relatively low burden. These episodes appear to be associated with a trend towards increased mortality but no effects on hospitalization or thrombo-embolism rates.