Cardiac activation–repolarization patterns and ion channel expression mapping in intact isolated normal human hearts

Opthof, Tobias; Remme, Carol Ann; Jorge, Esther; Noriega, Francisco J.; Wiegerinck, Rob F.; Tasiam, A.; Beekman, Leander; Álvarez‐García, Jesús; Munoz-Guijosa, Cristian; Coronel, Ruben; Cinca, Juan

doi:10.1016/j.hrthm.2016.10.010

Cited by 42 publications

(36 citation statements)

References 20 publications

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“…In addition we used a G Ks gradient related to the activation sequence. A recent study by Opthof et al in 3 explanted normal human hearts has shown quite different patterns of heterogeneity [31]. It cannot be excluded that some results of our sensitivity analysis would have been different in the presence of these different baseline patterns.…”

Section: Limitationsmentioning

confidence: 74%

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients

Sánchez

Sante

Maffessanti

et al. 2017

Med Biol Eng Comput

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Cardiac resynchronization therapy is not effective in a variable proportion of heart failure patients. An accurate knowledge of each patient's electroanatomical features could be helpful to determine the most appropriate treatment. The goal of this study was to analyze and quantify the sensitivity of left ventricular (LV) activation and the electrocardiogram (ECG) to changes in 39 parameters used to tune realistic anatomical-electrophysiological models of the heart. Electrical activity in the ventricles was simulated using a reaction-diffusion equation. To simulate cellular electrophysiology, the Ten Tusscher-Panfilov 2006 model was used. Intracardiac electrograms and 12-lead ECGs were computed by solving the bidomain equation. Parameters showing the highest sensitivity values were similar in the six patients studied. QRS complex and LV activation times were modulated by the sodium current, the cell surface-to-volume ratio in the LV, and tissue conductivities. The T-wave was modulated by the calcium and rectifier-potassium currents, and the cell surface-to-volume ratio in both ventricles. We conclude that homogeneous changes in ionic currents entail similar effects in all ECG leads, whereas the effects of changes in tissue properties show larger inter-lead variability. The effects of parameter variations are highly consistent between patients and most of the model tuning could be performed with only ~10 parameters.

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Section: Limitationsmentioning

confidence: 74%

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients

Sánchez

Sante

Maffessanti

et al. 2017

Med Biol Eng Comput

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“…The recent study by Opthof et al is unique in that it used detailed RV and LV measurements in all layers [2].…”

Section: Td-tr Slopes In Patients With Heart Failurementioning

confidence: 99%

“…Individual values of the slope of the relation between depolarization and repolarization times in previous studies and in the present one. O = Opthof et al [1,2], F is Franz et al, [18], C1 and C2 are the CABG and aortic stenosis patients, respectively of the Cowan study [4]. All data refer to LV measurements, except in the non-LBBB and LBBB patients, where values from the combined measurements were used.…”

Section: Disclosuresmentioning

confidence: 99%

“…This concordance can only be understood if the main direction of repolarization is opposite to that of the preceding depolarization, in other words, that the latest depolarizing regions repolarize first. Indeed, many studies in animals and relatively healthy humans observed an inverse relation between the time of depolarization (TD) and repolarization (TR) of a region [1][2][3]. Less negative or even positive TD-TR relations have been observed in small groups of patients with aortic valve stenosis, coinciding with smaller or discordant T-waves [4,5].…”

Section: Introductionmentioning

confidence: 99%

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The relation between local repolarization and T-wave morphology in heart failure patients

Maffessanti

Wanten

Potse

et al. 2017

International Journal of Cardiology

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“…In addition to the transmural electrical gradient, there is also evidence of electrical heterogeneity between the apex to base (Autenrieth et al, 1975;Watanabe et al, 1985;Franz et al, 1987) and left to right ventricles of the heart (Durrer et al, 1970;Srinivasan et al, 2016). Indeed, whole heart studies have shown that the T wave is an index of dispersion of repolarization across the whole heart and not due to transmural electrical gradients (Meijborg et al, 2014;Opthof et al, 2017;Srinivasan et al, 2019).…”

Section: Cardiac Ventricular Repolarization and The Surface Ecg T Wavementioning

confidence: 99%

Low-Frequency Oscillations in Cardiac Sympathetic Neuronal Activity

Ang

Marina

2020

Front. Physiol.

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Sudden cardiac death caused by ventricular arrhythmias is among the leading causes of mortality, with approximately half of all deaths attributed to heart disease worldwide. Periodic repolarization dynamics (PRD) is a novel marker of repolarization instability and strong predictor of death in patients post-myocardial infarction that is believed to occur in association with low-frequency oscillations in sympathetic nerve activity. However, this hypothesis is based on associations of PRD with indices of sympathetic activity that are not directly linked to cardiac function, such as muscle vasoconstrictor activity and the variability of cardiovascular autospectra. In this review article, we critically evaluate existing scientific evidence obtained primarily in experimental animal models, with the aim of identifying the neuronal networks responsible for the generation of low-frequency sympathetic rhythms along the neurocardiac axis. We discuss the functional significance of rhythmic sympathetic activity on neurotransmission efficacy and explore its role in the pathogenesis of ventricular repolarization instability. Most importantly, we discuss important gaps in our knowledge that require further investigation in order to confirm the hypothesis that low frequency cardiac sympathetic oscillations play a causative role in the generation of PRD.

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Cardiac activation–repolarization patterns and ion channel expression mapping in intact isolated normal human hearts

Abstract: In the normal human heart, repolarization gradients encompass all axes, without late midmural repolarization. Last activated areas do not repolarize first as previously assumed. Gradients of mRNAs of single ion channel subunits and of ARIs do not correlate.

Cited by 42 publications

References 20 publications

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients

The relation between local repolarization and T-wave morphology in heart failure patients

Low-Frequency Oscillations in Cardiac Sympathetic Neuronal Activity

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