Bruno Dubé

A Comparison of Monodomain and Bidomain Reaction-Diffusion Models for Action Potential Propagation in the Human Heart

A bidomain reaction-diffusion model of the human heart was developed, and potentials resulting from normal depolarization and repolarization were compared with results from a compatible monodomain model. Comparisons were made for an empty isolated heart and for a heart with fluid-filled ventricles. Both sinus rhythm and ectopic activation were simulated. The bidomain model took 2 days on 32 processors to simulate a complete cardiac cycle. Differences between monodomain and bidomain results were extremely small, even for the extracellular potentials, which in case of the monodomain model were computed with a high-resolution forward model. Propagation of activation was 2% faster in the bidomain model than in the monodomain model. Electrograms computed with monodomain and bidomain models were visually indistinguishable. We conclude that, in the absence of applied currents, propagating action potentials on the scale of a human heart can be studied with a monodomain model

Wavelet time entropy, T wave morphology and myocardial ischemia

Using wavelets, the authors computed the entropy of the signal at various frequency levels (wavelet time entropy) and, thus, find an optimal measure to differentiate normal states from ischemic ones. This new indicator is independent from the ST segment and yet provide a conclusive detection of the ischemic states.

Cardiac anisotropy in boundary-element models for the electrocardiogram

The boundary-element method (BEM) is widely used for electrocardiogram (ECG) simulation. Its major disadvantage is its perceived inability to deal with the anisotropic electric conductivity of the myocardial interstitium, which led researchers to represent only intracellular anisotropy or neglect anisotropy altogether. We computed ECGs with a BEM model based on dipole sources that accounted for a “compound” anisotropy ratio. The ECGs were compared with those computed by a finite-difference model, in which intracellular and interstitial anisotropy could be represented without compromise. For a given set of conductivities, we always found a compound anisotropy value that led to acceptable differences between BEM and finite-difference results. In contrast, a fully isotropic model produced unacceptably large differences. A model that accounted only for intracellular anisotropy showed intermediate performance. We conclude that using a compound anisotropy ratio allows BEM-based ECG models to more accurately represent both anisotropies.

A computer heart model incorporating anisotropic propagation. III. Simulation of ectopic beats.

With the advent of catheter ablation procedures, it has become an important goal to predict noninvasively the site of origin of ventricular tachycardia. Site classifications based on the observed body surface potential maps (BSPMs) during ventricular endocardial pacing, as well as on the patterns of the QRS integrals of these maps, have been suggested. The goals of this study were to verify these maps and their QRS integral patterns via simulation using a computer heart model with realistic geometry and to determine whether the model could improve clinical understanding of these ectopic patterns. Simulation was achieved by initiating excitation of the heart model at different endocardial sites and their overlying epicardial counterparts. This excitation propagated in anisotropic fashion in the myocardium. Retrograde excitation of the models His-Purkinje conduction system was necessary to obtain realistic activation durations. Simulated BSPMs, computed by placing the heart model inside a numerical torso model, and their QRS integrals were close to those observed clinically. Small differences in QRS integral map patterns and in the positions of the QRS integral map extrema were noted for endocardial sites in the left septal and anteroseptal regions. The simulated BSPMs during early QRS for an endocardial site and its epicardial counterpart tended to be mirror images about the zero isopotential contour, exchanging positive and negative map regions. The simulation results attest to the models ability to reproduce accurately clinically recorded body surface potential distributions obtained following endocardial stimulation. The QRS integral maps from endocardial sites in the left septal and anteroseptal regions were the most labile, owing to considerable cancellation effects. Conventional BSPMs can be useful to help distinguish between endocardial and epicardial ectopic sites.

Effect of the renin-angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients.

Objective To determine the effects of 8 weeks of therapy with amlodipine, ramipril or telmisartan on the autonomic system over 24 h in hypertensives. Methods After a placebo run-in, 57 patients were included in a prospective randomized open-label design protocol for therapy with amlodipine (5 mg for 4 weeks followed by 10 mg for 4 weeks, n = 22), or ramipril (2.5 mg for 1 week, 5.0 mg for 3 weeks and 10 mg for 4 weeks, n = 17) or telmisartan (80 mg for 8 weeks, n = 18). Autonomic functions were assessed by norepinephrine (NE) and epinephrine (E), as well as by the spectral analysis of heart rate variability (HRV). Results The 24-h ambulatory blood pressure, plasma NE and HRV demonstrated the characteristic day–night circadian rhythm in hypertensives. Higher values for SBP and DBP and for NE levels, as well as for spectral analysis components – low frequency band (LF) and low frequency/high frequency (LF/HF) ratio – were found during the day, whereas the HF was higher during the night. In patients treated with amlodipine, the HF decreased significantly during the night, while the LF and the LF/HF ratio increased during the day in association with the rise in NE. The therapy with telmisartan did increase the HF during the night and the day, while ramipril did not influence all HRV components during the night but significantly increased the HF, and decreased the LF/HF ratio during the day. No changes were observed in plasma NE with telmisartan or ramipril, but a 50% increase in NE levels throughout the 24-h period was found in amlodipine-treated patients. Conclusion These data suggest a sympathetic activation during the day and a decrease in parasympathetic activity during the night after therapy with amlodipine, correlated with increases in plasma NE. In contrast, the therapy with telmisartan significantly increased parasympathetic activity without changes in NE during the night and day. The therapy with ramipril increased the parasympathetic activity only during the day.

Simulation of QRST integral maps with a membrane-based computer heart model employing parallel processing

The simulation of the propagation of electrical activity in a membrane-based realistic-geometry computer model of the ventricles of the human heart, using the governing monodomain reaction-diffusion equation, is described. Each model point is represented by the phase 1 Luo-Rudy membrane model, modified to represent human action potentials. A separate longer duration action potential was used for the M cells found in the ventricular midwall. Cardiac fiber rotation across the ventricular wall was implemented via an analytic equation, resulting in a spatially varying anisotropic conductivity tensor and, consequently, anisotropic propagation. Since the model comprises approximately 12.5 million points, parallel processing on a multiprocessor computer was used to cut down on simulation time. The simulation of normal activation as well as that of ectopic beats is described. The hypothesis that in situ electrotonic coupling in the myocardium can diminish the gradients of action-potential duration across the ventricular wall was also verified in the model simulations. Finally, the sensitivity of QRST integral maps to local alterations in action-potential duration was investigated.

Localization of cardiac ectopic activity in man by a single moving dipole. Comparison of different computation techniques

The accuracy of different computation techniques for the non-invasive localization of cardiac ectopic activity was evaluated. Body surface potentials were recorded from 63 leads in 14 patients with implanted pacemakers. The location, orientation and magnitude of a single moving dipole (SMD) were computed from the first eight terms of a truncated multipole expansion estimated from the body surface potentials. The SMD trajectories obtained during the QRS complex were plotted along with the heart outlines and pacing leads obtained independently from chest x-rays. The origin of the SMD trajectories was compared to the position of the pacing lead to evaluate the accuracy of the SMD. The optimum computation technique used a least-squares (LS) estimation of the multipole expansion truncated at 15 multipoles, in conjunction with a torso model that included regions of lower conductivity representing the lungs. With this method, the SMD trajectories originated near the pacing lead (25 +/- 12 mm) and adequately represented the progression of the ectopic wavefront across the entire heart silhouette. With the LS techniques using 8 or 24 multipoles, the spans of the trajectories were respectively too short, or too long to cover the heart, and the average distance between the SMD at QRS onset and the pacing lead was larger. With a surface integration technique, the SMD-pacing lead distances were similar, both for a finite homogeneous torso model with a fixed geometry, as well as for torso models adapted to the torso geometry of each patient. The SMD was found adequate to represent the progression of an ectopic wavefront, and to localize its origin in man.

A Computer Heart Model Incorporating Anisotropic Propagation IV. Simulation of Regional Myocardial Ischemia

The main goal of this study was to simulate clinical body surface potential maps, recorded during percutaneous transluminal coronary angioplasty protocols, using a realistic geometry computer heart model. Other objectives were to address the question of reciprocal ST-segment changes observed in the 12-lead electrocardiogram during ischemia and to verify the hypothesis that the shortening of the QRS duration observed in left anterior descending (LAD) coronary artery occlusion may be explained by conduction delay in the septal His-Purkinje system. Simulation was achieved by first introducing into the heart model three transmural zones of mild, moderate, and severe ischemia for assumed occlusions in the LAD, left circumflex, and right coronary arteries. The heart model was then excited, in turn, with these three zones present for assumed occlusions in the LAD, left circumflex, and right coronary arteries. Myocardial conduction velocities in the regions of moderate and severe ischemia were assumed to be reduced to 75 and 50% of normal, respectively. Model action potentials in the mild, moderate, and severely ischemic zones were also altered to reflect known ischemic changes in these action potentials. Body surface potential maps and electrocardiograms were computed by placing the heart inside a numerical torso model. Simulated map patterns during both ST-segment and QRS were qualitatively similar to clinical maps. Reciprocal ST-segment depression was observed for all three occlusions in remote leads that did not overlie the ischemic zones. QRS shortening due to septal His-Purkinje conduction delay was verified. The simulation results attest to the models ability to reproduce body surface potential distributions recorded following percutaneous transluminal coronary angioplasty protocols. The simulations also showed that reciprocal ST-segment changes occur as a natural consequence of the primary ischemic region and that there is no need to invoke a second region of ischemia. Finally, the model demonstrated that QRS shortening can occur in LAD occlusion despite a slowing of conduction down the septal His-Purkinje system.

Evaluation of a subject-specific transfer-function-based nonlinear QT interval rate-correction method.

The QT interval in the electrocardiogram (ECG) is a measure of total duration of depolarization and repolarization. Correction for heart rate is necessary to provide a single intrinsic physiological value that can be compared between subjects and within the same subject under different conditions. Standard formulas for the corrected QT (QTc) do not fully reproduce the complexity of the dependence in the preceding interbeat intervals (RR) and inter-subject variability. In this paper, a subject-specific, nonlinear, transfer function-based correction method is formulated to compute the QTc from Holter ECG recordings. The model includes five parameters: three describing the static QT-RR relationship and two representing memory/hysteresis effects that intervene in the calculation of effective RR values. The parameter identification procedure is designed to minimize QTc fluctuations and enforce zero correlation between QTc and effective RR. Weighted regression is used to better handle unbalanced or skewed RR distributions. The proposed optimization approach provides a general mathematical framework for further extensions of the model. Validation, robustness evaluation and comparison with existing QT correction formulas is performed on ECG signals recorded during sinus rhythm, atrial pacing, tilt-table tests, stress tests and atrial flutter (29 subjects in total). The resulting average modeling error on the QTc is 4.9 ± 1.1 ms with a sampling interval of 2 ms, which outperforms correction formulas currently used. The results demonstrate the benefits of subject-specific rate correction and hysteresis reduction.

Attenuation of Autonomic Nervous System Functions in Hypertensive Patients at Rest and During Orthostatic Stimulation

The effect of age on autonomic nervous system was assessed at rest and while standing using systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, and power spectral analysis of the time duration between 2 consecutive R waves of an electrocardiogram (RR) interval variability, as well as on plasma norepinephrine and epinephrine levels in mild to moderate hypertensive patients (DBP, 90–110 mm Hg). Patients younger than 60 years (n=57) and older than 60 years (n=32), were evaluated after a 3‐ to 4‐week placebo period. Plasma catecholamines were measured in the supine position at rest and after 10 minutes of standing. Power spectral analysis of the RR interval variability was performed in each condition using the high‐frequency (HF) band (0.15–0.4 Hz) as an index of parasympathetic activity and the low‐frequency (LF) band (0.05–0.15 Hz) and LF‐HF ratio to estimate sympathetic activity. The total power was calculated as the sum of LF and HF power. supine SBP was significantly higher in older patients (P<.05). SBP and DBP increased significantly only in younger patients during standing (P<.05), while the changes were smaller and nonsignificantly lower in older patients. HR was similar in both groups at rest and increased similarly during standing. Norepinephrine and epinephrine levels were similar at rest and increased similarly in both groups of patients during standing. At rest, lower LF and HF components were observed in older patients. The LF component increased less and the HF component decreased less in older patients during standing. A lower sympathetic and parasympathetic basal cardiac tone was observed at rest in older hypertensive patients. Moreover, reduced hemodynamic and sympathetic responses to standing as assessed by SBP, DBP, and the LF component of HR variability were observed in older hypertensives in the presence of a normal catecholamine response. These observations could reflect a decreased sensitivity of cardiac β‐adrenoceptors with aging.