Automated Framework for the Inclusion of a His–Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology

AbstractPersonalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing.

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Arrhythmia susceptibility in senescent rat hearts

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2014.2143 ◽

2014 ◽

Vol 87 (1) ◽

Author(s):

Stefano Rossi ◽

Silvana Baruffi ◽

Domenico Corradi ◽

Sergio Callegari ◽

Ezio Musso ◽

...

Keyword(s):

Cardiac Electrophysiology ◽

The Elderly ◽

Detailed Knowledge ◽

Activation Patterns ◽

Electrophysiological Properties ◽

Age Related ◽

Rat Hearts ◽

Arrhythmogenic Substrate ◽

Ventricular Activation

Cardiovascular disease increases with age as well as alterations of cardiac electrophysiological properties, but a detailed knowledge about changes in cardiac electrophysiology relevant to arrhythmogenesis in the elderly is relatively lacking. The aim of this study was to determine specific age-related changes in electrophysiological properties of the ventricles which can be related to a structural-functional arrhythmogenic substrate. Multiple epicardial electrograms were recorded on the ventricular surface of in vivo control and aged rats, while arrhythmia vulnerability was investigated by premature stimulation protocols. Single or multiple ectopic beats and sustained ventricular arrhythmias were frequently induced in aged but not in control hearts. Abnormal ventricular activation patterns during sinus rhythm and unchanged conduction velocity during point stimulation in aged hearts suggest the occurrence of impaired impulse conduction through the distal Purkinje system that might create a potential reentry substrate.

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Modelling of patient-specific Purkinje activation based on measured ECGs

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2017-0177 ◽

2017 ◽

Vol 3 (2) ◽

pp. 171-174 ◽

Cited By ~ 2

Author(s):

Willi Kahlmann ◽

Emanuel Poremba ◽

Danila Potyagaylo ◽

Olaf Dössel ◽

Axel Loewe

Keyword(s):

Cardiac Electrophysiology ◽

Ventricular Myocardium ◽

Patient Specific ◽

Minimal Distance ◽

Fast Marching ◽

Desktop Computer ◽

Complete Evaluation ◽

Purkinje System ◽

Surface Ecg

AbstractThe Purkinje system is part of the fast-conducting ventricular excitation system. The anatomy of the Purkinje system varies from person to person and imposes a unique excitation pattern on the ventricular myocardium, which defines the morphology of the QRS complex of the ECG to a large degree. While it cannot be imaged in-vivo, it plays an important role for personalizing computer simulations of cardiac electrophysiology. Here, we present a new method to automatically model and customize the Purkinje system based on the measured electrocardiogram (ECG) of a patient. A graphbased algorithm was developed to generate Purkinje systems based on the parameters fibre density, minimal distance from the atrium, conduction velocity, and position and timing of excitation sources mimicking the bundle branches. Based on the resulting stimulation profile, the activation times of the ventricles were calculated using the fast marching approach. Predescribed action potentials and a finite element lead field matrix were employed to obtain surface ECG signals. The root mean square error (RMSE) between the simulated and measured QRS complexes of the ECGs was used as cost function to perform optimization of the Purkinje parameters. One complete evaluation from Purkinje tree generation to the simulated ECG could be computed in about 10 seconds on a standard desktop computer. The measured ECG of the patient used to build the anatomical model was matched via parallel simplex optimization with a remaining RMSE of 4.05 mV in about 16 hours. The approach presented here allows to tailor the structure of the Purkinje system through the measured ECG in a patient-specific way. The computationally efficient implementation facilitates global optimization.

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Ventricular activation is impaired in aged rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00517.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. H2336-H2347 ◽

Cited By ~ 30

Author(s):

Stefano Rossi ◽

Silvana Baruffi ◽

Andrea Bertuzzi ◽

Michele Miragoli ◽

Domenico Corradi ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Elderly Population ◽

The Elderly ◽

Ventricular Myocardium ◽

Conduction System ◽

Aged Rats ◽

Activation Time ◽

Activation Patterns ◽

Electrophysiological Properties ◽

Ventricular Activation

Ventricular arrhythmias are frequently observed in the elderly population secondary to alterations of electrophysiological properties that occur with the normal aging process of the heart. However, the underlying mechanisms remain poorly understood. The aim of the present study was to determine specific age-related changes in electrophysiological properties and myocardial structure in the ventricles that can be related to a structural-functional arrhythmogenic substrate. Multiple unipolar electrograms were recorded in vivo on the anterior ventricular surface of four control and seven aged rats during normal sinus rhythm and ventricular pacing. Electrical data were related to morphometric and immunohistochemical parameters of the underlying ventricular myocardium. In aged hearts total ventricular activation time was significantly delayed (QRS duration: +69%), while ventricular conduction velocity did not change significantly compared with control hearts. Moreover, ventricular activation patterns displayed variable numbers of epicardial breakthrough points whose appearance could change with time. Morphological analysis in aged rats revealed that heart weight and myocyte transverse diameter increased significantly, scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium, and gap junction connexin expression decreased significantly in ventricular myocardium compared with control rats. Our results show that in aged hearts delayed total ventricular activation time and abnormal activation patterns are not due to delayed myocardial conduction and suggest the occurrence of impaired impulse propagation through the conduction system leading to uncoordinated myocardial excitation. Impaired interaction between the conduction system and ventricular myocardium might create a potential reentry substrate, contributing to a higher incidence of ventricular arrhythmias in the elderly population.

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Electrocardiogram (ECG) patterns of left anterior fascicular block and conduction impairment in ventricular myocardium: a whole-heart model-based simulation study

Journal of Zhejiang University SCIENCE B ◽

10.1631/jzus.b1700029 ◽

2018 ◽

Vol 19 (1) ◽

pp. 49-56 ◽

Cited By ~ 4

Author(s):

Yuan Gao ◽

Ling Xia ◽

Ying-lan Gong ◽

Ding-chang Zheng

Keyword(s):

Simulation Study ◽

Ventricular Myocardium ◽

Heart Model ◽

Model Based ◽

Whole Heart ◽

Electrocardiogram Ecg

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Abstract 15430: Comparison of Ventricular Activation Time in Sinus and His Bundle Paced Beats

Circulation ◽

10.1161/circ.142.suppl_3.15430 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Cited By ~ 1

Author(s):

Shakeel Jamal ◽

Beth Bailey ◽

Rehan Mahmud

Keyword(s):

Comparative Analysis ◽

Left Ventricular ◽

Conduction Time ◽

Activation Time ◽

Excitation Wave ◽

His Bundle ◽

Purkinje System ◽

Ventricular Activation ◽

The Relationship ◽

Lower Voltage

Introduction: The relationship between conduction time of a sinus impulse and a paced impulse from His bundle to peak of left ventricular activation (HVAT) has not been systematically studied. Hypothesis: To perform a comparative analysis of HVAT of sinus and paced impulse in non-selective (NS) His bundle pacing (HBP) and selective (S)-HBP. Furthermore, to determine if pacing voltage and presence of His Purkinje system (HPS) disease affects HVAT. Methods: In 102 consecutive patients a comparative analysis of native HVAT and paced HVAT at higher (5-volt) and lower voltage (1-volt) was done in all patients and in groups subdivided into NS-HBP, S-HBP, with and without HPS disease. Results: Compared to sinus HVAT (105.9 ± 24.0 ms), paced HVAT was shorter at 5-volt (97.2 ± 17.9 ms) ( p<0.01 ) and longer at 1-volt ( p<0.01 ). This voltage effect was significant only in NS-HBP (-15.8 ± 15.7 ms, p<0.01 ) but not in selective-HBP (-6.2± 13.6 ms p=0.16 ). In NS-HBP, decrease in HVAT caused by 5-volt was the same in normal vs diseased HPS (-14.5 ± 12.8 vs-13.2 ±16.3 ms). Conclusions: 1) Compared to sinus HVAT, NS-HBP HVAT is significantly shorter at 5-volt, however, tends to prolong at 1-volt.2) The 1-volt to 5-volt HVAT decrease appears to be similar both normal and diseased NS-HBP thus not related to correction of HPS delay. 3) The voltage related decrease in HVAT is significant in presence of pre-excitation wave seen in NS-HBP and is not significant in S-HBP.

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Stretch–excitation correlation in the toad heart

Journal of Experimental Biology ◽

10.1242/jeb.228882 ◽

2020 ◽

Vol 223 (23) ◽

pp. jeb228882

Author(s):

Vladimir A. Vityazev ◽

Jan E. Azarov

Keyword(s):

Bolus Injection ◽

Ventricular Myocardium ◽

Bufo Bufo ◽

Interquartile Range ◽

Video Recordings ◽

Ventricular Activation ◽

Potential Mapping ◽

Activation Times ◽

The Right ◽

Activation Sequence

ABSTRACTThe activation sequence of the ventricular myocardium in ectotherms is a matter of debate. We studied the correlation between the ventricular activation sequence and the pattern of local stretches in 13 toads (Bufo bufo). Epicardial potential mapping was done with a 56-lead sock array. Activation times were determined as dV/dt (min) in each lead. Initial epicardial foci of activation were found on the left side of the ventricular base, whereas regions on the apex and the right side of the base demonstrated late activation. Video recordings (50 frames s−1) showed that the median presystolic stretch in left-side ventricular regions was greater than that in right-side regions [4.70% (interquartile range 3.25–8.85%) versus 1.45% (interquartile range 0.38–3.05%), P=0.028, respectively]. Intracardiac bolus injection elicited ventricular activation with a similar sequence and duration. Thus, ventricular areas of earliest activation were associated with greater presystolic stretch, implying the existence of a stretch–excitation relationship in ectotherm hearts.

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