Computational model of erratic arrhythmias in a cardiac cell network: the role of gap junctions.

Cardiac morbidity and mortality increases with the population age. To investigate the underlying pathological mechanisms, and suggest new ways to reduce clinical risks, computational approaches complementing experimental and clinical investigations are becoming more and more important. Here we explore the possible processes leading to the occasional onset and termination of the (usually) non-fatal arrhythmias widely observed in the heart. Using a computational model of a two-dimensional network of cardiac cells, we tested the hypothesis that an ischemia alters the properties of the gap junctions inside the ischemic area. In particular, in agreement with experimental findings, we assumed that an ischemic episode can alter the gap junctions of the affected cells by reducing their average conductance. We extended these changes to include random fluctuations with time, and modifications in the gap junction rectifying conductive properties of cells along the edges of the ischemic area. The results demonstrate how these alterations can qualitatively give an account of all the main types of non-fatal arrhythmia observed experimentally, and suggest how premature beats can be eliminated in three different ways: a) with a relatively small surgical procedure, b) with a pharmacological reduction of the rectifying conductive properties of the gap-junctions, and c) by pharmacologically decreasing the gap junction conductance. In conclusion, our model strongly supports the hypothesis that non-fatal arrhythmias can develop from post-ischemic alteration of the electrical connectivity in a relatively small area of the cardiac cell network, and suggests experimentally testable predictions on their possible treatments.

Prediction of sudden death in heart failure patients: a novel perspective from the assessment of the peak ectopy rate.

AIMS: In patients with heart failure (HF), the association between sudden death and arrhythmic pattern at 24-h Holter monitoring [number of ventricular premature contractions per hour (VPCs/h) and presence of non-sustained ventricular tachycardia (NSVT)] has previously been investigated with conflicting results. Since both VPCs/h and NSVT disregard the time course of arrhythmic events, we developed a new index based on the short-term peak rate of ectopies and investigated its prognostic power in HF patients. METHODS AND RESULTS: We studied 200 HF patients in sinus rhythm [age: [median (interquartile range)] 54 years [47-58], left ventricular ejection fraction (LVEF): 23% [19-28], New York Heart Association (NYHA) class II-III: 88%]. For each patient, the Holter recording was automatically scanned shifting a 30 beat window one beat at a time, and the maximum number of ectopic beats found in a window was named peak ectopy rate (PEAK_ER). The association between PEAK_ER and sudden death was assessed by Cox proportional hazards regression analysis. Survival analysis was also carried out adjusting for NYHA class, aetiology, LVEF, left ventricular end diastolic diameter, blood urea nitrogen, amiodarone, Digoxin, beta-blockers, NSVT, VPCs/h, and the standard deviation of all normal-to-normal beats. During a 5-year follow-up [31 (12-60) months], 23 patients died of sudden death. Out of the arrhythmic markers, PEAK_ER but not VPCs/h and NSVT was significantly associated with sudden death in univariable analysis (RR: 1.08, 95% CI: 1.02-1.14, P = 0.005) and after adjustment for covariates (RR: 1.09, 95% CI: 1.03-1.15, P = 0.004). CONCLUSIONS: The investigation of the time course of arrhythmic events provides independent information in the identification of patients at increased risk of sudden death and may therefore be considered in the development of treatment strategies in HF patients.

Analysis of implantable cardioverter defibrillator signals for non conventional cardiac electrical activity characterization.

Implantable cardioverter defibrillators (ICDs) can store intracardiac electrograms (EGMs) in sinus rhythm (SR), at the onset of spontaneous ventricular tachyarrhythmias (VT) or during their course. This allows the investigation of unknown features of the heart electrical activity associated with different cardiac rhythms. In this study we propose a non conventional cardiac electrical activity characterization (CEAC) that extracts quantitative information about the power spectrum wideness and variability of the beat-by-beat morphology. We analyze 293 EGMs from 40 patients who underwent implantation of St Jude Medical-Ventritex ICDs that allow the storage of EGMs with two different modes of recording: bipolar (BIP) and unipolar or far-field (FF). The EGMs are studied with this CEAC by (1) exploring differences between the CEAC measured from FF and BIP EGMs during similar cardiac rhythms, and (2) investigating the mode of recording that allows a better separation between SR and VT rhythms. Results show that, with similar cardiac rhythm, the CEACs from FF or BIP recordings are different (for SR rhythm: sensitivity 81.5%, specificity 93.6%; for VT rhythm: sensitivity and specificity 100%); thus FF and BIP EGMs analyze different aspects of cardiac activity. The CEAC applied to FF EGMs distinguishes better EGMs obtained during SR from VT rhythms (VT vs SR with sensitivity 92.7% and specificity 79.7%) than when it is applied to BIP signals (VT vs SR with sensitivity 60% and specificity 73.3%).