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5. Transmural Ventricular Heterogeneities Play a Major Role in Determining T-Wave Morphology at Different Extracellular Potassium Levels

Author

Bukhari, H.A., Palmieri, F., Ferreira, D., Potse, M., Ramírez, J., Laguna, P., Sánchez, C., Pueyo, E., Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Laboratorios Rubió, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Queen Mary University of London (QMUL), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), This work was supported by projects ERC-2014-StG 638284 (ERC), DPI2016-75458-R (MINECO), MarieSkłodowska-Curie grant 764738 and Aragón Government, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 0206 medical engineering, 02 engineering and technology, [MATH]Mathematics [math], 020601 biomedical engineering
Abstract

International audience; End-stage renal disease (ESRD) affects more than 10% of the world population. ESRD patients present impaired potassium homeostasis, which increases the risk for ventricular arrhythmias and sudden cardiac death. Noninvasive estimation of serum potassium, [K+], before the patient experiences serious consequences is of major importance. In this study, we investigated the relationship of [K+] with three T-wave morphological descriptors: the T-wave width (Tw), slope-to-amplitude ratio (TSA) and temporal morphological variability (dw) from ECGs of 12 ESRD patients undergoing hemodialysis and from simulated ECGs. Spearman’s correlation coefficients between the descriptors Tw, TSA and dw and [K+] were -0.5, 0.8 and 0.65, respectively. These associations were, however, highly patient-dependent. The high inter-individual variability in T-wave morphology, particularly observed at high [K+], was reproduced in the simulations and could be explained by differences in transmural heterogeneities, with 10% variations in the proportion of midmyocardial cells leading to changes larger than 15% in T-wave morphology. In conclusion, T-wave morphological descriptors have the potential to be used as predictors of [K+] in ESRD patients, but their associated inter-individual variability should be taken into account, especially under hyperkalemic conditions.

Published
2019

6. A left bundle branch block activation sequence and ventricular pacing influence voltage amplitudes: an in vivo and in silico study

Author

Nguyen, U.C., Potse, M., Vernooy, K., Mafi-Rad, M., Heijman, J., Caputo, M.L., Conte, G., Regoli, F., Krause, R., Moccetti, T., Auricchio, A., Prinzen, F.W., Maffessanti, F., Nguyen, U.C., Potse, M., Vernooy, K., Mafi-Rad, M., Heijman, J., Caputo, M.L., Conte, G., Regoli, F., Krause, R., Moccetti, T., Auricchio, A., Prinzen, F.W., and Maffessanti, F.

Abstract

Item does not contain fulltext, Aims: The aim of this study was to investigate the influence of the activation sequence on voltage amplitudes by evaluating regional voltage differences during a left bundle branch block (LBBB) activation sequence vs. a normal synchronous activation sequence and by evaluating pacing-induced voltage differences. Methods and results: Twenty-one patients and three computer models without scar were studied. Regional voltage amplitudes were evaluated in nine LBBB patients who underwent endocardial electro-anatomic mapping (EAM). Pacing-induced voltage differences were evaluated in 12 patients who underwent epicardial EAM during intrinsic rhythm and right ventricular (RV) pacing. Three computer models customized for LBBB patients were created. Changes in voltage amplitudes after an LBBB (intrinsic), a normal synchronous, an RV pacing, and a left ventricular pacing activation sequence were assessed in the computer models. Unipolar voltage amplitudes in patients were approximately 4.5 mV (4.4-4.7 mV, approximately 33%) lower in the septum when compared with other segments. A normal synchronous activation sequence in the computer models normalized voltage amplitudes in the septum. Pacing-induced differences were larger in electrograms with higher voltage amplitudes during intrinsic rhythm and furthermore larger and more variable at the epicardium [mean absolute difference: 3.6-6.2 mV, 40-53% of intrinsic value; interquartile range (IQR) differences: 53-63% of intrinsic value] compared to the endocardium (mean absolute difference: 3.3-3.8 mV, 28-30% of intrinsic value; IQR differences: 37-40% of intrinsic value). Conclusion: In patients and computer models without scar, lower septal unipolar voltage amplitudes are exclusively associated with an LBBB activation sequence. Pacing substantially affects voltage amplitudes, particularly at the epicardium.

Published
2018

9. Do we need to enforce the homogeneous Neumann condition on the torso for solving the inverse electrocardiographic problem?

Author

Judit Chamorro Servent, Bear, L., Duchateau, J., Potse, M., Dubois, R., Coudiere, Y., IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SPI]Engineering Sciences [physics], [MATH]Mathematics [math]
Abstract

Robust calculations of the inverse electrocardiographic problem may require accurate specification of boundary conditions at the torso and cardiac surfaces. In particular, the numerical specification of the no-flux condition on the torso is difficult because surface normals must be computed, and because the torso may alternatively be considered infinitely far away from the heart. Using the method of fundamental solutions (MFS) proposed in [1], this boundary conditions can be taken into account in different manners. Specifically, the no-flux condition on the torso can be ignored, or weighted with respect to the Dirichlet boundary condition associated to the torso data, or can be strongly enforced through a saddle-point problem. In this article, we compare these approaches. In this work we provide a preliminary comparison of these different strategies. This study received financial support from the French Government as part of the “Investissements d’avenir” program managed by the National Research Agency (ANR), Grant reference ANR-10-IAHU-04 and from the Conseil R´egional Aquitaine as part of the project “Assimilation de donn´ees en canc´erologie et cardiologie”.

Published
2016

17. Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40

Author

van Rijen, H. V., van Veen, T. A., van Kempen, M. J., Wilms-Schopman, F. J., Potse, M., Krueger, O., Willecke, K., Opthof, T., Jongsma, H. J., de Bakker, J. M., Other departments, ACS - Amsterdam Cardiovascular Sciences, and Cardiology

Subjects
sense organs
Abstract

Connexin (Cx)40 and Cx45 are the major protein subunits of gap junction channels in the conduction system of mammals. To determine the role of Cx40, we correlated cardiac activation with Connexin distribution in normal and Cx40-deficient mice hearts. Epicardial and septal activation was recorded in Langendorff-perfused adult mice hearts with a 247-point compound electrode (interelectrode distance, 0.3 mm). After electrophysiological measurements, hearts were prepared for immunohistochemistry and histology to determine Connexin distribution and fibrosis. In both wild-type and Cx40-deficient animals, epicardial activation patterns were similar. The right and left ventricular septum was invariably activated from base to apex. Histology revealed a continuity of myocytes from the common bundle to the septal myocardium. Within this continuity, colocalization was found of Cx43 and Cx45 but not of Cx40 and Cx43. Both animals showed similar His-bundle activation. In Cx40-deficient mice, the proximal bundle branches expressed Cx45 only. The absence of Cx40 in the proximal bundles correlated with right bundle-branch block. Conduction in the left bundle branch was impaired as compared with wild-type animals. Our data show that (1) in mice, a continuity exists between the common bundle and the septum, and (2) Cx40 deficiency results in right bundle-branch block and impaired left bundle-branch conduction

Published
2001

19. Electrocardiographic identification of abnormal ventricular depolarization and repolarization in patients with idiopathic ventricular fibrillation

Author

Peeters, H. A., SippensGroenewegen, A., Wever, E. F., Potse, M., Daniëls, M. C., Grimbergen, C. A., Hauer, R. N., Robles de Medina, E. O., and Other departments

Abstract

We sought to gain more insight into the arrhythmogenic etiology of idiopathic ventricular fibrillation (VF) by assessing ventricular depolarization and repolarization properties by means of various electrocardiographic (ECG) techniques. Idiopathic VF occurs in the absence of demonstrable structural heart disease. Abnormalities in ventricular depolarization or repolarization have been related to increased vulnerability to VF in various cardiac disorders and are possibly also present in patients with idiopathic VF. In 17 patients with a first episode of idiopathic VF, 62-lead body surface QRST integral maps, QT dispersion on the 12-lead ECG and XYZ-lead signal-averaged ECGs were computed. All subjects of a healthy control group had a normal dipolar QRST integral map. In patients with idiopathic VF, either a normal dipolar map (29%,), a dipolar map with an abnormally large negative area on the right side of the thorax (24%) or a nondipolar map (47%) were recorded. Only four patients (24%) had increased QT dispersion on the 12-lead ECG and late potentials could be recorded in 6 (38%) of 16 patients. During a median follow-up duration of 56 months (range 9 to 136), a recurrent arrhythmic event occurred in 7 patients (41%), all of whom had an abnormal QRST integral map. Five of these patients had late potentials, and three showed increased QT dispersion on the 12-lead ECG. In patients with idiopathic VF, ventricular areas of slow conduction, regionally delayed repolarization or dispersion in repolarization can be identified. Therefore, various electrophysiologic conditions, alone or in combination, may be responsible for the occurrence of idiopathic VF. Body surface QRST integral mapping may be a promising method to identify those patients who do not show a recurrent episode of VF

Published
1998

33. The positive T wave.

Author

Potse M, Coronel R, Opthol T, and Vinet A

Abstract

OBJECTIVE: The instant of maximum slope (Tup) of the T wave in the unipolar electrogram is a well-established measure of repolarisation time (TR). Nevertheless, recent observations on positive T waves have caused a renewed debate. The purpose of this study was to elucidate the mechanism that leads to positive and negative T waves and to investigate which electrogram feature best predicts TR. METHODS: We simulated propagating action potentials (AP) and electrograms with a bidomain reaction-diffusion model of the human heart including heterogeneous ion-channel properties. To explain positive T waves we compared results with those of a much simpler model, which predicts T waves from local and remote AP. RESULTS: Repolarisation time was defined as the instant of steepest downstroke of the AP. T wave polarity was mostly determined by TR. Positive T waves occurred at early-repolarising sites. Correlation between Tup and TR was >0.99, in both negative and positive T waves. T wave area and peak value also correlated highly with TR. CONCLUSION: The polarity of the T wave is primarily determined by TR. Positive T waves occur at early-repolarising sites. Local TR is best estimated by Tup, also in positive T waves. [ABSTRACT FROM AUTHOR]

Published
2007

34. Understanding ST depression in the stress-test ECG.

Author

Potse M, Vinet A, LeBlanc A, Diodati JG, and Nadeau R

Abstract

OBJECTIVE: The electrocardiogram (ECG) obtained during stress testing often shows a typical pattern of primary ST depression. A similar pattern can occur in unstable angina. Current textbooks consider ST depression as a direct result of partial occlusion of a coronary artery. However, animal models could not reproduce this phenomenon. An alternative explanation for ST depression specific to stress testing involves global subendocardial ischemia. In this study, we evaluated both explanations with a realistic mathematical model of the human heart. METHODS: The ECG was simulated with an anisotropic reaction-diffusion model of the human heart and an inhomogeneous boundary-element model of the human torso. RESULTS: Limited subendocardial ischemic zones caused small ST depression in ECG leads not overlying the ischemic region. An ischemic zone of 50% transmural extent covering the entire left ventricular subendocardium caused an ST-depression pattern similar to that observed during stress test. CONCLUSION: In contrast to regional subendocardial ischemia, global subendocardial ischemia can explain ST depression in our model. [ABSTRACT FROM AUTHOR]

Published
2007

41. Why do we need supercomputers to understand the electrocardiographic T wave?

Author

Potse M, LeBlanc A, and Vinet A

Abstract

OBJECTIVE: Propagation of depolarisation and repolarisation in myocardium results from an interplay of membrane potential, transmembrane current, and intercellular current. This process can be represented mathematically with a reaction-diffusion (RD) equation. Solving RD equations for a whole heart requires a supercomputer. Therefore, earlier models used predefined action potential (AP) shapes and fixed propagation velocities. We discuss why RD models are important when T waves are studied. METHODS: We simulated propagating AP with an RD model of the human heart, which included heterogeneity of membrane properties. Computed activation times served as input to a model that used predefined AP, and to a 'hybrid model' that computed AP only during repolarisation. The hybrid model was tested with different spatial resolutions. Electrocardiograms (ECGs) were computed with all three models. RESULTS: Computed QRS complexes were practically identical in all models. T waves in the fixed-AP model had 20 to 40% larger amplitudes in leads V1-V3. The hybrid model produced the same T waves as the RD model at 0.25-mm resolution, but underestimated T-wave amplitude at lower resolutions. CONCLUSION: Fixed AP waveforms in a forward ECG model lead to exaggerated T waves. Hybrid models require the same high spatial resolution as RD models. [ABSTRACT FROM AUTHOR]

Published
2007

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