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Atrial fibrillation (AF) and congestive heart failure (CHF) are the most prevalent types of cardiovascular disorders as the leading cause of death due to delayed diagnosis. Early diagnosis of these cardiac conditions is possible by manually analyzing electrocardiogram (ECG) signals. However, manual diagnosis is complex, owing to the various characteristics of ECG signals. An accurate classification system for AF and CHF has the potential to save patient lives. Therefore, this study proposed an ECG signal classification system for AF and CHF using a one-dimensional convolutional neural network (1-D CNN) to provide a robust classification system performance. This study used ECG signal recording of AF, CHF, and NSR, which can be accessed on the Physionet website. A total of 5600 ECG signal segments were obtained from 56 subjects, divided into train sets from 42 subjects (N = 4200 ECG segments), and test sets from 14 subjects (N = 1400). We applied for leave-one-out cross-validation in training to select the best model. The proposed 1-D CNN algorithm successfully classified raw data of ECG signals into normal sinus rhythm (NSR), AF, and CHF by providing the highest classification accuracy of 99.643%, f1-score, recall, and precision of 0.996, respectively, with an AUC score of 0.999. The results showed that the proposed method extracted the ECG signal information directly without needing several preprocessing steps and feature extraction methods that potentially reduce the information contained in the ECG signals. Furthermore, the proposed method outperformed previous studies in classifying AF, CHF, and NSR. Therefore, this approach can be considered as an adjunct for medical personnel to diagnose AF, CHF, and NSR.

Cardiovascular disorders, including atrial fibrillation (AF) and congestive heart failure (CHF), are the significant causes of mortality worldwide. The diagnosis of cardiovascular disorders is heavily reliant on ECG signals. Therefore, extracting significant features from ECG signals is the most challenging aspect of representing each condition of ECG signal. Earlier studies have claimed that the Hjorth descriptor is assigned as a simple feature extraction algorithm capable of class separation among AF, CHF, and normal sinus rhythm (NSR) conditions. However, due to noise interference, certain features do not represent the characteristics of the ECG signals. This study addressed this critical gap by applying the discrete wavelet transform (DWT) to decompose the ECG signals into sub-bands and extracting Hjorth descriptor features and entropy-based features in the DWT domain. Therefore, the calculation of Hjorth descriptor and entropy-based features performed on each sub-band will produce more detailed information of ECG signals. The optimization of various classifier algorithms, including k-nearest neighbor (k-NN), support vector machine (SVM), random forest (RF), artificial neural network (ANN), and radial basis function network (RBFN), was investigated to provide the best system performance. This study obtained an accuracy of 100% for the k-NN, SVM, RF, and ANN classifiers, respectively, and 97% for the RBFN classifier. The results demonstrated that the optimization of the classifier algorithm could improve the classification accuracy of AF, CHF, and NSR conditions, compared to earlier studies.

Ventricular fibrillation (VF) is a cardiovascular disease that is one of the major causes of mortality worldwide, according to the World Health Organization. Heart rate variability (HRV) is a biomarker that is used for detecting and predicting life-threatening arrhythmias. Predicting the occurrence of VF in advance is important for saving patients from sudden death. We extracted features from seven HRV data lengths to predict the onset of VF before nine different forecast times and observed the prediction accuracies. By using only five features, an artificial neural network classifier was trained and validated based on 10-fold cross-validation. Maximum prediction accuracies of 88.18% and 88.64% were observed at HRV data lengths of 10 and 20 s, respectively, at a forecast time of 0 s. The worst prediction accuracy was recorded at an HRV data length of 70 s and a forecast time of 80 s. Our results showed that features extracted from HRV signals near the VF onset could yield relatively high VF prediction accuracies.

Myocardial fibrosis is an integral component of most forms of heart failure. Clinical and computational studies have reported that spatial fibrosis pattern and fibrosis amount play a significant role in ventricular arrhythmogenicity. This study investigated the effect of the spatial distribution of fibrosis and fibrosis amount on the electrophysiology and mechanical performance of the human ventricles. Seventy-five fibrosis distributions comprising diffuse, patchy, and compact fibrosis types that contain 10–50% fibrosis amount were generated. The spatial fibrosis distribution was quantified using the fibrosis entropy (FE) metric. Electrical simulations under reentry conditions induced using the S1–S2 protocol were conducted to investigate the fibrosis arrhythmogenicity. We also performed mechanical simulations to examine the influence of the fibrosis amount and the spatial distribution of fibrosis on the pumping efficacy of the LV. We observed that the mean FE of the compact type is the largest among the three types. The electrical simulation results revealed that the ventricular arrhythmogenicity of diffuse fibrosis depends on the fibrosis amount and marginally on the spatial distribution of fibrosis. Meanwhile, the ventricular arrhythmogenicity of the compact and patchy fibrosis pattern is more reliant on the spatial distribution of fibrosis than on the fibrosis amount. The average number of phase singularities (PSs) in the compact fibrosis pattern was the highest among the three patterns of fibrosis. The diffuse type of fibrosis has the lowest average number of PSs than that in the patchy and compact fibrosis. The reduction in the stroke volume (SV) showed high influence from the electrical instabilities induced by the fibrosis amount and pattern. The compact fibrosis exhibited the lowest SV among the three patterns except in the 40% fibrosis amount. In conclusion, the fibrosis pattern is as crucial as the fibrosis amount for sustaining and aggravating ventricular arrhythmogenesis.

The KCNH2 L532P mutation is an alteration in the IKr channel that is associated with short QT syndrome and atrial fibrillation in zebrafish. In preliminary studies, the electrophysiological effects of the hERG L532P mutation were investigated using a mathematical model in a single-cell and 2D sheet medium. The objective of this study was to quantify the effects of the KCNH2 L532P mutation on the 3D ventricular electrophysiological behavior and the mechanical pumping responses. We used a realistic three-dimensional ventricular electrophysiological-mechanical model, which was adjusted into two conditions: the wild-type (WT) condition, i.e., the original case of the Tusscher et al. model, and the L532P mutation condition, with modification of the original IKr equation. The action potential duration (APD) in the mutant ventricle was reduced by 73% owing to the significant increase of the IKr current density. In the 3D simulation, the L532P mutation maintained the sustainability of reentrant waves; however, the reentry was terminated in the WT condition. The contractility of the ventricle with L532P mutation was significantly reduced compared with that in WT which results in sustain shivering heart during reentry condition. The reduction of the contractility was associated with the shortening APD which simultaneously shortened the duration of the Ca2+ channel opening. In conclusion, the ventricle with KCNH2 L532P mutation is prone to reentry generation with a sustained chaotic condition, and the mutation significantly reduced the pumping performance of the ventricles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Atrial arrhythmia is a cardiac disorder caused by abnormal electrical signaling and transmission, which can result in atrial fibrillation and eventual death. Genetic defects in ion channels can cause myocardial repolarization disorders. Arrhythmia-associated gene mutations, including KCNH2 gene mutations, which are one of the most common genetic disorders, have been reported. This mutation causes abnormal QT intervals by a gain of function in the rapid delayed rectifier potassium channel (IKr). In this study, we demonstrated that mutations in the KCNH2 gene cause atrial arrhythmia. Methods The N588K and L532P mutations were induced in the Courtemanche-Ramirez-Nattel (CRN) cell model, which was subjected to two-dimensional and three-dimensional simulations to compare the electrical conduction patterns of the wild-type and mutant-type genes. Results In contrast to the early self-termination of the wild-type conduction waveforms, the conduction waveform of the mutant-type retained the reentrant wave (N588K) and caused a spiral break-up, resulting in irregular wave generation (L532P). Conclusion The present study confirmed that the KCNH2 gene mutation increases the vulnerability of the atrial tissue for arrhythmia.

Electromechanical delay (EMD) is the time interval between local myocyte depolarization and the onset of myofiber shortening. Previously, researchers measured EMD during sinus rhythm and ectopic pacing in normal and heart failure conditions. However, to our knowledge, there are no reports regarding EMD during another type of rhythms or arrhythmia. The goal of this study was to quantify EMD during sinus rhythm, tachycardia, and ventricular fibrillation conditions. We hypothesized that EMD under sinus rhythm is longer due to isovolumetric contraction which is imprecise during arrhythmia. We used a realistic model of 3D electromechanical ventricles. During sinus rhythm, EMD was measured in the last cycle of cardiac systole under steady conditions. EMD under tachycardia and fibrillation conditions was measured during the entire simulation, resulting in multiple EMD values. We assessed EMD for the following 3 conduction velocities (CVs): 31 cm/s, 51 cm/s, and 69 cm/s. The average EMD during fibrillation condition was the shortest corresponding to 53.45 ms, 55.07 ms, and 50.77 ms, for the CVs of 31 cm/s, 51 cm/s, and 69 cm/s, respectively. The average EMD during tachycardia was 58.61 ms, 58.33 ms, and 52.50 ms for the three CVs. Under sinus rhythm with action potential duration restitution (APDR) slope 0.7, the average EMD was 66.35 ms, 66.41 ms, and 66.60 ms in line with the three CVs. This result supports our hypothesis that EMD under sinus rhythm is longer than that under tachyarrhythmia conditions. In conclusion, this study observed and quantified EMD under tachycardia and ventricular fibrillation conditions. This simulation study has widened our understanding of EMD in 3D ventricles under chaotic conditions.

This study hypothesized that a left ventricular assist device (LVAD) shortens the electromechanical delay (EMD) by mechanical unloading. The goal of this study is to examine, by computational modeling, the influence of LVAD on EMD for four heart failure (HF) cases ranging from mild HF to severe HF. We constructed an integrated model of an LVAD-implanted cardiovascular system, then we altered the Ca2+ transient magnitude, with scaling factors 1, 0.9, 0.8, and 0.7 representing HF1, HF2, HF3, and HF4, respectively, in order of increasing HF severity. The four HF conditions are classified into two groups. Group one is the four HF conditions without LVAD, and group two is the conditions treated with continuous LVAD pump. The single-cell mechanical responses showed that EMD was prolonged with the higher load. The findings indicated that in group one, the HF-induced Ca2 + transient remodeling prolonged the mechanical activation time (MAT) and decreased the contractile tension, which reduced the left ventricle (LV) pressure, and increased the end-diastolic strain. In group two, LVAD shortened MAT of the ventricles. Furthermore, LVAD reduced the contractile tension, and end-diastolic strain, but increased the aortic pressure. The computational study demonstrated that LVAD shortens EMD by mechanical unloading of the ventricle. Electronic supplementary material The online version of this article (10.1007/s11517-017-1730-y) contains supplementary material, which is available to authorized users.

The KCNJ2 gene mutations induce short QT syndrome (SQT3) by directly increasing the IK1 current. There have been many studies on the electrophysiological effects of mutations such as the KCNJ2 D172N that cause the SQT3. However, the KCNJ2 E299V mutation is distinguished from other representative gene mutations that can induce the short QT syndrome (SQT3) in that it increased IK1 current by impairing the inward rectification of K+ channels. The studies of the electromechanical effects on myocardial cells and mechanisms of E299V mutations are limited. Therefore, we investigated the electrophysiological changes and the concomitant mechanical responses according to the expression levels of the KCNJ2 E299V mutation during sinus rhythm and ventricular fibrillation. We performed excitation-contraction coupling simulations using a human ventricular model with both electrophysiological and mechanical properties. In order to observe the electromechanical changes due to the expression of KCNJ2 E299V mutation, the simulations were performed under normal condition (WT), heterogeneous mutation condition (WT/E299V), and pure mutation condition (E299V). First, a single-cell simulation was performed in three types of ventricular cells (endocardial cell, midmyocardial cell, and epicardial cell) to confirm the electrophysiological changes and arrhythmogenesis caused by the KCNJ2 E299V mutation. In three-dimensional sinus rhythm simulations, we compared electrical changes and the corresponding changes in mechanical performance caused by the expression level of E299V mutation. Then, we observed the electromechanical properties of the E299V mutation during ventricular fibrillation using the three-dimensional reentry simulation. The KCNJ2 E299V mutation accelerated the opening of the IK1 channel and increased IK1 current, resulting in a decrease in action potential duration. Accordingly, the QT interval was reduced by 48% and 60% compared to the WT condition, for the WT/E299V and E299V conditions, respectively. During sustained reentry, the wavelength was reduced due to the KCNJ2 E299V mutation. Furthermore, there was almost no ventricular contraction in both WT/E299V and E299V conditions. We concluded that in both sinus rhythm and fibrillation, the KCNJ2 E299V mutation results in very low contractility regardless of the expression level of mutation and increases the risk of cardiac arrest and cardiac death.

Early prediction of the occurrence of ventricular tachyarrhythmia (VTA) has a potential to save patients’ lives. VTA includes ventricular tachycardia (VT) and ventricular fibrillation (VF). Several studies have achieved promising performances in predicting VT and VF using traditional heart rate variability (HRV) features. However, as VTA is a life-threatening heart condition, its prediction performance requires further improvement. To improve the performance of predicting VF, we used the QRS complex shape features, and traditional HRV features were also used for comparison. We extracted features from 120-s-long HRV and electrocardiogram (ECG) signals (QRS complex signed area and R-peak amplitude) to predict the VF onset 30 s before its occurrence. Two artificial neural network (ANN) classifiers were trained and tested with two feature sets derived from HRV and the QRS complex shape based on a 10-fold cross-validation. The prediction accuracy estimated using 11 HRV features was 72%, while that estimated using four QRS complex shape features yielded a high prediction accuracy of 98.6%. The QRS complex shape could play a significant role in performance improvement of predicting the occurrence of VF. Thus, the results of our study can be considered by the researchers who are developing an application for an implantable cardiac defibrillator (ICD) when to begin ventricular defibrillation.

Purpose Although the quantitative analysis of electromechanical alternans is important, previous studies have focused on electrical alternans, and there is a lack quantitative analysis of mechanical alternans at the subcellular level according to various basic cycle lengths (BCLs). Therefore, we used the excitation–contraction (E–C) coupling model of human ventricular cells to quantitatively analyze the mechanical alternans of ventricular cells according to various BCLs. Methods To implement E–C coupling, we used calcium transient data, which is the output data of electrical simulation using the electrophysiological model of human ventricular myocytes, as the input data of mechanical simulation using the contractile myofilament dynamics model. Moreover, we applied various loads on ventricular cells for implementation of isotonic and isometric contraction. Results As the BCL was reduced from 1000 to 200 ms at 30 ms increments, mechanical alternans, as well as electrical alternans, were observed. At this time, the myocardial diastolic tension increased, and the contractile ATP consumption rate remained greater than zero even in the resting state. Furthermore, the time of peak tension, equivalent cell length, and contractile ATP consumption rate were all reduced. There are two tendencies that endocardial, mid-myocardial, and epicardial cells have the maximum amplitude of tension and the peak systolic tension begins to appear at a high rate under the isometric condition at a particular BCL. Conclusions We observed mechanical alternans of ventricular myocytes as well as electrical alternans, and identified unstable conditions associated with mechanical alternans. We also determined the amount of BCL given to each ventricular cell to generate stable and high tension state in the case of isometric contraction.

Highlights • We numerically investigated the physiological relationship between the severity of regurgitation and the effect of a left ventricular assist device (LVAD) on cardiovascular system responses. • Under conditions of mitral regurgitation, the effects of both pulsatile and continuous LVAD treatment on ventricular unloading were significant. • Under conditions of aortic regurgitation (AR), the effects of the LVADs on ventricular unloading were not significant. The effects of LVAD treatment decreased according to the severity of AR., Background A left ventricular assist device (LVAD) is normally contraindicated in significant aortic regurgitation (AR) and requires intraoperative valve repair or exclusion. Nevertheless, AR can coexist with an LVAD, so a valid question when asked might still be of clinical significance. The purpose of this study is to analyze the effects of valve regurgitation on the pumping efficacy of continuous and pulsatile LVADs with a computational method. Methods A cardiovascular model was developed based on the Windkessel model, which reflects the hemodynamic flow resistance and the blood wall elasticity. Using the Windkessel model, important cardiovascular components, such as the right atrium, right ventricle, pulmonary artery, pulmonary vein, left atrium (LA), left ventricle (LV), aorta, and branching blood vessels, were expressed. Results In the case of AR, continuous and pulsatile LVADs improved cardiac output and reduced mechanical load slightly. In the case of mitral regurgitation, the LVADs improved cardiac output (cardiac outputs were about 5 L/min regardless of the severity of regurgitation) and reduced afterload significantly. Conclusion AR reduced both continuous and pulsatile LVAD function significantly while mitral regurgitation did not affect their pumping efficacy.

Death due to ventricular fibrillation (VF) can occur over a relatively short time period. During the first stage, an irregular heartbeat or arrhythmia of the heart may occur. Therefore, studying arrhythmia could reveal important insights relevant to the prevention of VF. One of the factors known to cause arrhythmia is the generation of mutations in the ion channels of myocytes. The current experimental methods to monitor and observe subjects with arrhythmia are invasive, and could possibly harm the subject with no guarantee of obtaining good results. These limitations could be overcome by using an extensively validated computational simulation study. This study aims to enhance our understanding of the effect of the V241F mutation on electromechanical behavior in the heart. We simulated three conditions; wild-type (WT), heterozygous/intermediate V241F, and pure V241F conditions in an electrophysiological single cell model and three-dimensional electro-mechanics ventricular model. The electro-mechanics model is a one-way coupling of the electrical compartment to the mechanical compartment by Ca2+ transient concentration. Consistent with a previous study, the V241F mutation significantly shortened the action potential duration at 90% repolarization (APD90) under pure V241F mutation conditions, due to the gain of function of the slow delayed rectifier potassium (IKs) channel. This APD90 shortening is associated with a short electrical wavelength, which shortens the Ca2+ activation time as well. The hemodynamic responses showed that the V241F mutation lowered ventricular contraction under normal sinus rhythm conditions by decreasing the stroke volume, stroke work, and ejection fraction. During reentry, the V241F mutation significantly reduced the ventricular contractility compared with the WT condition. In conclusions, the effect of the two variants of V241F (intermediate and pure) mutation not only disturbed the electrophysiological events but also affected the mechanical behavior significantly. The result of this study can be used as a reference for the cardiovascular expert to decide the appropriate pharmacology of IKs conductance block for the patient.

The understanding of cardiac arrhythmia under genetic mutations has grown in interest among researchers. Previous studies focused on the effect of the D172N mutation on electrophysiological behavior. In this study, we analyzed not only the electrophysiological activity but also the mechanical responses during normal sinus rhythm and reentry conditions by using computational modeling. We simulated four different ventricular conditions including normal case of ten Tusscher model 2006 (TTM), wild-type (WT), heterozygous (WT/D172N), and homozygous D172N mutation. The 2D simulation result (in wire-shaped mesh) showed the WT/D172N and D172N mutation shortened the action potential duration by 14%, and by 23%, respectively. The 3D electrophysiological simulation results showed that the electrical wavelength between TTM and WT conditions were identical. Under sinus rhythm condition, the WT/D172N and D172N reduced the pumping efficacy with a lower left ventricle (LV) and aortic pressures, stroke volume, ejection fraction, and cardiac output. Under the reentry conditions, the WT condition has a small probability of reentry. However, in the event of reentry, WT has shown the most severe condition. Furthermore, we found that the position of the rotor or the scroll wave substantially influenced the ventricular pumping efficacy during arrhythmia. If the rotor stays in the LV, it will cause very poor pumping performance. Graphical Abstract A model of a ventricular electromechanical system. This whole model was established to observe the effect of D172N KCNJ2 mutation on ventricular pumping behavior during sinus rhythm and reentry conditions. The model consists of two components; electrical component and mechanical component. The electrophysiological model based on ten Tusscher et al. with the IK1 D172N KCNJ2 mutation, and the myofilament dynamic (cross-bridge) model based on Rice et al. study. The 3D electrical component is a ventricular geometry based on MRI which composed of nodes representing single-cell with electrophysiological activation. The 3D ventricular mechanic is a finite element mesh composed of single-cells myofilament dynamic model. Both components were coupled with Ca2+ concentration. We used Gaussian points for the calcium interpolation from the electrical mesh to the mechanical mesh.

The KCNQ1 S140G mutation, which is involved in IKs current, affects atrial fibrillation. However, little is known about its effect on the mechanical behavior of the heart. Therefore, we assessed the influence of the KCNQ1 S140G mutation on ventricular electrophysiological stability and mechanical pumping performance using a multi-scale model of cardiac electromechanics. An image-based electromechanical model was used to assess the effect on electrical propagation and arrhythmogenesis of the KCNQ1 S140G mutation. In addition, it was used to compare the mechanical response under the wild-type (WT) and S140G mutation conditions. The intracellular calcium transient obtained from the electrophysiological model was applied as an input parameter to a mechanical model to implement excitation–contraction coupling. The IKs current equation was modified to account for expression of the KCNQ1 S140G mutation, and it included a scaling factor (ϕ) for mutant expressivity. The WT and S140G mutation conditions were compared at the single-cell and three-dimensional (3D) tissue levels. The action potential duration (APD) was reduced by 60% by the augmented IKs current under the S140G mutation condition, which resulted in shorter QT interval. This reduced the 3D sinus rhythm wavelength by 60% and the sustained re-entry by 56%. However, pumping efficiency of mutant ventricles was superior in sinus rhythm condition. In addition, the shortened wavelength in cardiac tissue allowed a re-entrant circuit to form and increased the probability of sustaining ventricular tachycardia and ventricular fibrillation. In contrast, under the WT condition, a normal wavelength (20.8 cm) was unlikely to initiate and sustain re-entry in the cardiac tissue. Subsequently, the S140G mutant ventricles developed a higher dominant frequency distribution range (2.0–5.3 Hz) than the WT condition (2.8–3.7 Hz). In addition, stroke volume of mutant ventricles was reduced by 65% in sustained re-entry compared to the WT condition. In conclusion, signs of the S140G mutation might be difficult to identify in sinus rhythm even though the mutant ventricles show shortened QT interval. This suggests that the KCNQ1 S140G mutation increases the risk of death by sudden cardiac arrest. In addition, the KCNQ1 S140G mutation can induce ventricular arrhythmia and lessen ventricular contractility under re-entrant conditions.

There is growing interest in genetic arrhythmia since mutations in gene which encodes the ion channel underlie numerous arrhythmias. Hasegawa et al reported that G229D mutation in KCNQ1 underlies atrial fibrillation due to significant shortening of action potential duration (APD) in atrial cells. Here, we predicted whether KCNQ1 G229D mutation affects ventricular fibrillation generation, although it shortens APD slightly compared with the atrial cell. We analyzed the effects of G229D mutation on electrical and mechanical ventricle behaviors (not considered in previous studies). We compared action potential shapes under wild-type and mutant conditions. Electrical wave propagations through ventricles were analyzed during sinus rhythm and reentrant conditions. I(Ks) enhancement due to G229D mutation shortened the APD in the ventricular cells (6%, 0.3%, and 8% for endo, M, and epi-cells, respectively). The shortened APD contributed to 7% shortening of QT intervals, 29% shortening of wavelengths, 20% decrease in intraventricular pressure, and increase in end-systolic volume 17%, end-diastolic volume 7%, and end-diastolic pressure 11%, which further resulted in reduction in stroke volume as well as cardiac output (28%), ejection fraction 33% stroke work 44%, and ATP consumption 28%. In short, using computational model of the ventricle, we predicted that G229D mutation decreased cardiac pumping efficacy and increased the vulnerability of ventricular fibrillation.

Background Counter-pulsation control (CPC) by ventricular assist devices (VADs) is believed to reduce cardiac load and increase coronary perfusion. However, patients with VADs have a higher risk of arrhythmia, which may cause the CPC to fail. Consequently, CPC has not been applied by VADs in clinical practice. The phase-locked loop (PLL) algorithm for CPC is readily implemented in VADs; however, it requires a normal, consistent heartbeat for adequate performance. When an arrhythmia occurs, the algorithm maintains a constant pumping rate despite the unstable heartbeat. Therefore, to apply the PLL algorithm to CPC, the hemodynamic effects of abnormal heartbeats must be analyzed. Objectives This study sought to predict the hemodynamic effects in patients undergoing CPC using VADs, based on electrocardiogram (ECG) data, including a wide range of heart rate (HR) changes caused by premature ventricular contraction (PVC) or other reasons. Methods A four-element Windkessel hemodynamic model was used to reproduce the patient’s aortic blood pressure in this study. ECG data from 15 patients with severe congestive heart failure were used to assess the effect of the CPC on the patients’ hemodynamic state. The input and output flow characteristics of the pulsatile VAD (LibraHeart I, Cervika, Korea) were measured using an ultrasound blood flow meter (TS410, Transonic, USA), with the aortic pressure maintained at 80–120 mmHg. All other patient conditions were also reproduced. Results In patients with PVCs or normal heartbeats, CPC controlled by a VAD reduced the cardiac load by 20 and 40%, respectively. When the HR was greater for other reasons, such as sinus tachycardia, simultaneous ejection from the heart and VAD was observed; however, the cardiac load was not increased by rapid cardiac contractions resulting from decreased left ventricle volume. These data suggest that the PLL algorithm reduces the cardiac load and maintains consistent hemodynamic changes.

The purpose of the study is to examine the effects of pacemaker location on cardiac pumping efficacy the-oretically. We used a three-dimensional finite element cardiac electromechanical model of canine ventricles with mod-els of the circulatory system. Electrical activation time for normal sinus rhythm and artificial pacing in apex, leftventricular free wall, and right ventricular free wall were obtained from electrophysiological model. We applied theelectrical activation time maps to the mechanical contraction model and obtained cardiac mechanical responses suchas myocardial contractile ATP consumption, stroke work, stroke volume, ejection fraction, and etc. Among three arti-ficial pacing methods, left ventricle pacing showed best performance in ventricular pumping efficacy.Key words: Cardiac electromechanical model, Electrical activation time, ATP consumption rate, Stroke work, Strokevolume I. 서 론 정상동성리듬(Normal sinus rhythm)에 의한 심실의 수축은 퍼킨제섬유의 빠른 전도에 의해 심내막에 균일하고 동시자극을 주게 되고 이 자극이 심내막에서 심외막으로 전달됨으로써, 거의 동시다발적으로 좌우심실의 수축이 일어나게 된다. 심실의 전기적 흥분이 전파되는 경로상에서 문제가 있거나 동시성이 깨어질 경우에 인공 심박조율기를 이식하여 인공적으로 심조율을 하게 된다. 일반적으로 인공 심장재동기화를시행할때, 심실전극도자는접근성의용이로일반적으로 우심실에 이식한다[1]. 그러나 의료장비 및 시술기술의 발전으로 우심실뿐 만 아니라 좌심실이나 심첨 등에도 이식을 할 수 있게 되었고, 우심실이 아닌 다른 부위에서 인공 심조율기를 이식하여 시행함으로써 어떠한 심장역학적 변화가 있는지를 알아보고자 하는 실험들이 시도되었다[2,3]. 최근 일부 연구에서 보면 우심실이 아닌 좌심실에서 인위적으로 조율을 하였을 때 심박출량의 개선을 보인다는 보고도 있었다[4]. 그러나 실험적 방법에 의한 결과들은대부분 심장기능을 가늠하는 직접적인 지표(심박출량, 압력-부피관계, 심장에 부여되는 기계적응력 및 에너지소모량 등)가 아니라 심전도 또는 혈관계의 혈압과 같은 간접적인 지표들이다. 현재 의료측정장비의 기술로는 아직까지 위와 같은 지표들을 측정하는 것은 불가능하다. 이의 대안으로 심장모델링 기술을 이용한 컴퓨터 시뮬레

Outflow cannulation site of left ventricular assist device(LVAD) chosen by considering anatomical structure of thoracic cavity and vascular system. Though outflow cannulation site influences blood perfusion at each branch, there is no standard rule or quantitative data. In this study, we computed the amount of blood perfusion at each arterial branch numerically according to outflow cannulation sites(ascending aorta, aortic arch, descending aorta). We generated computational meshes to the three-dimensionally reconstructed arterial system. Clinically measured arterial pressure were used for inlet boundary condition, porous media were applied to mimic blood flow resistance. Blood perfusion through left common carotid artery was 2.5 times higher than other cases, and that through right common carotid artery was 1.1 times higher than other branches. Although this is simulation study, will be useful reference data for the clinical study of LVAD which considers blood perfusion efficiency.

Using a three-dimensional electromechanical model of the canine ventricles with dyssynchronous heart failure, we investigated the relationship between severity of valve regurgitation and ventricular mechanical responses. The results demonstrated that end-systolic tension in the septum and left ventricular free wall was significantly lower under the condition of mitral regurgitation (MR) than under aortic regurgitation (AR). Stroke work in AR was higher than that in MR. On the other hand, the difference in stroke volume between the two conditions was not significant, indicating that AR may cause worse pumping efficiency than MR in terms of consumed energy and performed work.

Background and aims Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. Methods In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Results Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. Conclusion LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

Background and aims Although studies on the relation between arrhythmias and the action potential duration (APD) have been carried out, most of them are based only on electrophysiological factors of the heart and lack experiments that consider cardiac mechanical and electromechanical characteristics. Therefore, we conducted this study to clarify the relevance of the shortening of APD of a cell in relation to the mechanical contraction activity of the heart and the associated risk of arrhythmia. Methods The human ventricular model used in this study has two dynamic characteristics: electrophysiological conduction and mechanical contraction. The model simulating electrophysiological characteristics was consisted of lumped parameter circuit that can mimic the phenomenon of ion exchange through the cell membrane of myocyte and consisted of 214,319 tetrahedral finite elements. In contrast, the model simulating mechanical contraction characteristics was constructed to mimic cardiac contraction by means of the crossbridge of a myofilament and consisted of 14,720 hermite-based finite elements to represent a natural 3D curve of the cardiac surface. First, we performed a single cell simulation and the electrophysiological simulation according to the change of the APD by changing the electrical conductivity of the I Ks channel. Thus, we confirmed the correlation between APD and intracellular Ca2+ concentration. Then, we compared mechanical response through mechanical simulation using Ca2+ data from electrical simulation. Results The APD and the sum of the intracellular Ca2+ concentrations showed a positive correlation. The shortened APD reduced the conduction wavelength of ventricular cells by shortening the plateau and early repolarization in myocardial cells. The decrease in APD reduced ventricular pumping efficiency by more than 60% as compared with the normal group (normal conditions). This change is caused by the decline of ventricular output owing to reduced ATP consumption during the crossbridge of myofilaments and decreased tension. Conclusion The shortening of APD owing to increased electrical conductivity of a protein channel on myocardial cells likely decreases the wavelength and the pumping efficiency of the ventricles. Additionally, it may increase tissue sensitivity to ventricular fibrillation, including reentry, and cause symptoms such as dyspnea and dizziness.

Genetic factors play an important role in the pathogenesis of atrial flutter (AF). Although mutation in KCNQ1 has been widely correlated with AF, the mechanism by which mutation promotes AF remains poorly understood. The purpose of this study was to investigate the proarrhythmic effect of V241F KCNQ1 mutation in human atrium using the electrophysiological model of human atrium. Using 2D and 3D cardiac electrophysiological models that incorporate the Courtemanche human atrial model, we simulated electrical conduction through atrial tissue and compared spiral wave dynamics under the wild-type and V241F KCNQ1 conditions. In 2D and 3D simulation, V241F KCNQ1 showed a stable and persistent wave without spiral break-up, whereas the wild-type wave was less stable, resulting in early self-termination. According to the results, we concluded that compared to the wild type, the electrical activity of the V241F KCNQ1 mutation is more likely to sustain spiral wave.

따라서 LVAD 처방의 장단점을 고려하여, 적절한 시기에 치료를 시작하는 것이 매우 중요하다. 특히 심실회복을 목표로 LVAD 치료를 시작하는 환Key Words: Left Ventricular Assist Device(좌심실보조장치), Ventricular Unloading(심실부하감소), Finite Element Model(유한요소감소모델), ATP Consumption(수축성 ATP소모율) 초록: 좌심실보조장치(LVAD)가 심실부하감소에 미치는 영향을 극대화 하기 위해, 심실보조장치 치료를 위한 최적의 심부전 심각도 단계를 찾는 것은 중요하다. 우리는 심부전 정도에 따른 LVAD 의 박동효율을 이론적으로 예측하였다. 우리는 혈관시스템의 6컴파트먼트의 Wind-kessel 모델과 연동된 심실의 삼차원 유한요소모델을 사용하였다. 이 모델을 이용하여, LVAD 치료 하에서 심부전의 정도에 따라 심실의 수축성 ATP 소모율, 좌심실압력, 심박출량, 심박출 분획, 1회심박출량 등과 같은 심장응답을 예측하였다. LVAD 치료 중에 에너지학적 부하조건을 암시하는 수축성 ATP 소모율은 5 단계 심부전 조건에서 가장 크게 감소하였다. 따라서, 우리는 LVAD 를 회복으로의 가교로서 고려하고 있을 때, 심부전 5 단계에서 LVAD 치료를 시작하는 것이 가장 적절하다는 결론을 내린다. Abstract: In order to maximize the effect of left ventricular assist device (LVAD) on ventricular unloading, the therapy should be begun at appropriate level of heart failure severity. We predicted pumping efficacy of LVAD according to the severity of heart failure theoretically. We used 3 dimensional finite element model of ventricle coupled with 6 Wind-kessel compartmental model of vascular system. Using the computational model, we predicted cardiac responses such as contractile ATP consumption of ventricle, left ventricular pressure, cardiac output, ejection fraction, and stroke work according to the severity of ventricular systolic dysfunction under the treatments of continuous LVAD. Contractile ATP consumption, which indicates the ventricular energetic loading condition decreased maximally at the 5

Intra-aortic balloon pump (IABP) is normally contraindicated in significant aortic regurgitation (AR). It causes and aggravates pre-existing AR while performing well in the event of mitral regurgitation (MR). Indirect parameters, such as the mean systolic pressure, product of heart rate and peak systolic pressure, and pressure-volume are used to quantify the effect of IABP on ventricular workload. However, to date, no studies have directly quantified the reduction in workload with IABP. The goal of this study is to examine the effect of IABP therapy on ventricular mechanics under valvular insufficiency by using a computational model of the heart. For this purpose, the 3D electromechanical model of the failing ventricles used in previous studies was coupled with a lumped parameter model of valvular regurgitation and the IABP-treated vascular system. The IABP therapy was disturbed in terms of reducing the myocardial tension generation and contractile ATP consumption by valvular regurgitation, particularly in the AR condition. The IABP worsened the problem of ventricular expansion induced as a result of the regurgitated blood volume during the diastole under the AR condition. The IABP reduced the LV stroke work in the AR, MR, and no regurgitation conditions. Therefore, the IABP helped the ventricle to pump blood and reduced the ventricular workload. In conclusion, the IABP partially performed its role in the MR condition. However, it was disturbed by the AR and worsened the cardiovascular responses that followed the AR. Therefore, this study computationally proved the reason for the clinical contraindication of IABP in AR patients.

Purpose: We developed a numerical model that predicts cardiovascular system response to hemodialysis, focusing on the effect of sodium profile during treatment. Materials and Methods: The model consists of a 2-compartment solute kinetics model, 3-compartment body fluid model, and 12-lumpedparameter representation of the cardiovascular circulation model connected to set-point models of the arterial baroreflexes. The solute kinetics model includes the dynamics of solutes in the intracellular and extracellular pools and a fluid balance model for the intracellular, interstitial, and plasma volumes. Perturbation due to hemodialysis treatment induces a pressure change in the blood vessels and the arterial baroreceptors then trigger control mechanisms (autoregulation system). These in turn alter heart rate, systemic arterial resistance, and cardiac contractility. The model parameters are based largely on the reported values. Results: We present the results obtained by numerical simulations of cardiovascular response during hemodialysis with 3 different dialysate sodium concentration profiles. In each case, dialysate sodium concentration profile was first calculated using an inverse algorithm according to plasma sodium concentration profiles, and then the percentage changes in each compartment pressure, heart rate, and systolic ventricular compliance and systemic arterial resistance during hemodialysis were determined. A plasma concentration with an upward convex curve profile produced a cardiovascular response more stable than linear or downward convex curves. Conclusion: By conducting numerical tests of dialysis/ cardivascular models for various treatment profiles and creating a database from the results, it should be possible to estimate an optimal sodium profile for each patient.

Atrial fibrillation (AF) is related to mutations at the genetic level. This includes mutations in genes that encode KCNQ1, a subunit of the I Ks channel. Here, we investigate the mechanism of gain-of-function in I Ks towards the occurrence of AF. We used the Courtemanche–Ramirez–Nattel (CRN) human atrial cell model (Am J Physiol Heart Circ Physiol 275:H301–H321, 1998) and applied the modification proposed by Hasegawa et al. (Heart Rhythm 11:67–75, 2014) to fit the behavior of I Ks due to the G229D mutation in KCNQ1 under a heterozygous mutant form. This was incorporated into two-(2D) and three-dimensional (3D) tissue models, where the mutation sustained a reentrant wave. However, under the wild-type condition, the reentrant wave terminated before the end of our simulations (in 2D, the spiral wave terminated before 10 s, while in 3D, the spiral wave terminated before 13 s). Sustained reentry under the mutation conditions also resulted in a spiral wave breakup in the 3D model, which was sustained until the end of the simulation (20 s), indicating AF.

Left ventricular-assist devices (LVADs) are used to supply blood to the body of patients with heart failure. Pressure unloading is greater for counter-pulsating LVADs than for continuous LVADs. However, several clinical trials have demonstrated that myocardial recovery is similar for both types of LVAD. This study examined the contractile energy consumption of the myocardium with continuous and counter-pulsating LVAD support to ascertain the effect of the different LVADs on myocardial recovery. We used a three-dimensional electromechanical model of canine ventricles, with models of the circulatory system and an LVAD. We compared the left ventricular peak pressure (LVPP) and contractile ATP consumption between pulsatile and continuous LVADs. With the continuous and counter-pulsating LVAD, the LVPP decreased to 46 and 10%, respectively, and contractile ATP consumption decreased to 60 and 50%. The small difference between the contractile ATP consumption of these two types of LVAD may explain the comparable effects of the two types on myocardial recovery.

To quantify the reduction in workload during intra-aortic balloon pump (IABP) therapy, indirect parameters are used, such as the mean arterial pressure during diastole, product of heart rate and peak systolic pressure, and pressure-volume area. Therefore, we investigated the cardiac energy consumption during IABP therapy using a cardiac electromechanics model. We incorporated an IABP function into a previously developed electromechanical model of the ventricle with a lumped model of the circulatory system and investigated the cardiac energy consumption at different IABP inflation volumes. When the IABP was used at inflation level 5, the cardiac output and stroke volume increased 11%, the ejection fraction increased 21%, the stroke work decreased 1%, the mean arterial pressure increased 10%, and the ATP consumption decreased 12%. These results show that although the ATP consumption is decreased significantly, stroke work is decreased only slightly, which indicates that the IABP helps the failed ventricle to pump blood efficiently.

Left ventricular assist device (LVAD) support under cannulation connected from the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart failure patients because it is non-invasive to ventricular muscle. However, it has serious problems, such as valve stenosis and blood thrombosis due to the low ejection fraction of the ventricle. We theoretically estimated the effect of the in-series cannulation, connected from ascending aorta to descending aorta (AA-DA), on ventricular unloading as an alternative to the LA-AA method. We developed a theoretical model of a LVAD-implanted cardiovascular system that included coronary circulation. Using this model, we compared hemodynamic responses according to various cannulation methods such as LA-AA, AA-DA, and a cannulation connected from the left ventricle to ascending aorta (LV-AA), under continuous and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left ventricular peak pressure than the LA-AA method under continuous and pulsatile LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing ventricular unloading whereas the AA-DA method is a better choice to increase coronary perfusion.

Background For blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods. Methods We devised a new mathematical lumped model to assess the toxin removal efficiency of blood purification systems in patients, integrating the mass transfer model for a human body with a dialyser. The human body model consists of a three-compartment model of body fluid dynamics and a two-compartment model of body solute kinetics. We simulated three types of blood purification therapy with the model, hemofiltration, hemodiafiltration, and high-flux dialysis, and compared the simulation results in terms of toxin (urea and beta-2 microglobulin) clearance and the treatment dose delivered under conditions of pulsatile and non-pulsatile pumping. In vivo experiments were also performed to verify the model results. Results Simulation results revealed that pulsatile flow improved the convective clearance of the dialyser and delivered treatment dose for all three types of therapy. Compared with the non-pulsatile pumping method, the increases in the clearance of urea and beta-2 microglobulin with pulsatile pumping were highest with hemofiltration treatment (122.7% and 122.7%, respectively), followed by hemodiafiltration (3.6% and 8.3%, respectively), and high-flux dialysis (1.9% and 4.7%, respectively). EKRc and std Kt/V averaged 28% and 23% higher, respectively, in the pulsatile group than in the non-pulsatile group with hemofiltration treatment. Conclusions The pulsatile effect was highly advantageous for all of the toxins in the hemofiltration treatment and for β2-microglobulin in the hemodiafiltration and high-flux dialysis treatments.

We developed a computational model to investigate the hemodynamic effects of a pulsatile left ventricular assist device (LVAD) on the cardiovascular system. The model consisted of 16 compartments for the cardiovascular system, including coronary circulation and LVAD, and autonomic nervous system control. A failed heart was modeled by decreasing the end-systolic elastance of the ventricle and blocking the mechanism controlling heart contractility. We assessed the physiological effect of the LVAD on the cardiovascular system for three types of LVAD flow: co-pulsation, counter-pulsation, and continuous flow modes. The results indicated that the pulsatile LVAD with counter-pulsation mode gave the most physiological coronary blood perfusion. In addition, the counter-pulsation mode resulted in a lower peak pressure of the left ventricle than the other modes, aiding cardiac recovery by reducing the ventricular afterload. In conclusion, these results indicate that, from the perspective of cardiovascular physiology, a pulsatile LVAD with counter-pulsation operation is a plausible alternative to the existing LVAD with continuous flow mode.

Background: When using a pulsatile left ventricular assist device (LVAD), it is important to reduce the cardiac load variations of the native heart because severe cardiac load variations can induce ventricular arrhythmia. In this study, we investigated the effect of counter-pulsation control of the LVAD on the reduction of cardiac load variation. Methods: A ventricular electrocardiogram-based counter-pulsation control algorithm for a LVAD was implemented, and the effects of counter-pulsation control of the LVAD on the reduction of the working load variations of the left ventricle were determined in three animal experiments. Results: Deviations of the working load of the left ventricle were reduced by 51.3%, 67.9%, and 71.5% in each case, and the beat-to-beat variation rates in the working load were reduced by 84.8%, 82.7%, and 88.2% in each ease after counter-pulsation control. There were 3 to 12 premature ventricle contractions (PVCs) before counter-pulsation control, but no PVCs were observed during counter-pulsation control. Conclusions: Counter-pulsation control of the pulsatile LVAD can reduce severe cardiac load variations, but the average working load is not markedly affected by application of counter-pulsation control because it is also influenced by temporary cardiac outflow variations. We believe that counter-pulsation control of the LVAD can improve the long-term safety of heart failure patients equipped with LVADs.