1.Clinical and pharmacological application of multiscale multiphysics heart simulator, UT-Heart
Jun Ichi OKADA ; Takumi WASHIO ; Seiryo SUGIURA ; Toshiaki HISADA
The Korean Journal of Physiology and Pharmacology 2019;23(5):295-303
A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining in vitro channel assays and in silico simulation of cardiac electrophysiology using UT-Heart successfully predicted druginduced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This in silico electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.
Blood Pressure
;
Cardiac Electrophysiology
;
Cardiac Resynchronization Therapy
;
Cardiotoxicity
;
Clinical Medicine
;
Computer Simulation
;
Drug Discovery
;
Drug Evaluation, Preclinical
;
Electrocardiography
;
Heart
;
Humans
;
In Vitro Techniques
;
Ion Channels
;
Models, Cardiovascular
;
Relaxation
;
Risk Assessment
2.In silico evaluation of the acute occlusion effect of coronary artery on cardiac electrophysiology and the body surface potential map.
Ah Jin RYU ; Kyung Eun LEE ; Soon Sung KWON ; Eun Seok SHIN ; Eun Bo SHIM
The Korean Journal of Physiology and Pharmacology 2019;23(1):71-79
Body surface potential map, an electric potential distribution on the body torso surface, enables us to infer the electrical activities of the heart. Therefore, observing electric potential projected to the torso surface can be highly useful for diagnosing heart diseases such as coronary occlusion. The BSPM for the heart of a patient show a higher level of sensitivity than 12-lead ECG. Relevant research has been mostly based on clinical statistics obtained from patients, and, therefore, a simulation for a variety of pathological phenomena of the heart is required. In this study, by using computer simulation, a body surface potential map was implemented according to various occlusion locations (distal, mid, proximal occlusion) in the left anterior descending coronary artery. Electrophysiological characteristics of the body surface during the ST segment period were observed and analyzed based on an ST isointegral map. We developed an integrated system that takes into account the cellular to organ levels, and performed simulation regarding the electrophysiological phenomena of the heart that occur during the first 5 minutes (stage 1) and 10 minutes (stage 2) after commencement of coronary occlusion. Subsequently, we calculated the bipolar angle and amplitude of the ST isointegral map, and observed the correlation between the relevant characteristics and the location of coronary occlusion. In the result, in the ventricle model during the stage 1, a wider area of ischemia led to counterclockwise rotation of the bipolar angle; and, during the stage 2, the amplitude increased when the ischemia area exceeded a certain size.
Cardiac Electrophysiology*
;
Computer Simulation*
;
Coronary Occlusion
;
Coronary Vessels*
;
Electrocardiography
;
Electrophysiological Phenomena
;
Electrophysiology
;
Heart
;
Heart Diseases
;
Humans
;
Ischemia
;
Torso
3.Meta-analysis on risk stratification of malignant ventricular tachyarrhythmic events in arrhythmogenic right ventricular cardiomyopathy.
Young Eun ROH ; Hyun Ji JANG ; Min Jung CHO
Yeungnam University Journal of Medicine 2017;34(2):208-215
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy characterized by predominant right ventricular fibro-fatty replacement, right ventricular dysfunction and ventricular arrhythmias. It is a rare but important cause of sudden cardiac death in children and young adults. A meta-analysis on risk stratification of major ventricular tachyarrhythmic events indicating the need for implantable cardioverter defibrillator therapy in ARVC was performed. METHODS: The pubmed database was searched from its inception to May 2015. Of the 433 citations identified, 12 were included in this meta-analysis. Data regarding major ventricular tachyarrhythmic events were retrieved in 817 subjects from the studies. For the variables, a combined odds ratio (OR) was calculated using a fixed-effects meta-analysis. RESULTS: Extensive right ventricular dysfunction (OR, 2.44), ventricular late potential (OR, 1.66), inducible ventricular tachyarrhythmia during electrophysiology study (OR, 3.67), non-sustained ventricular tachycardia (OR, 3.78), and history of fatal event/sustained VT (OR, 5.66) identified as significant risk factors (p < 0.0001). CONCLUSION: This meta-analysis shows that extensive right ventricular dysfunction, ventricular late potential, inducible ventricular tachyarrhythmia during electrophysiological study, non-sustained ventricular tachycardia, and history of sustained ventricular tachycardia/fibrillation are consistently reported risk factors of major ventricular tachyarrhythmic events indicating implantable cardioverter defibrillator therapy in patients with ARVC.
Arrhythmias, Cardiac
;
Arrhythmogenic Right Ventricular Dysplasia*
;
Cardiomyopathies
;
Child
;
Death, Sudden
;
Death, Sudden, Cardiac
;
Defibrillators
;
Electrophysiology
;
Humans
;
Odds Ratio
;
Risk Factors
;
Tachycardia
;
Tachycardia, Ventricular
;
Ventricular Dysfunction, Right
;
Young Adult
4.Ondansetron Inhibits Voltage-Gated K⁺ Current of Ventricular Myocytes from Pregnant Mouse.
Shanyu CUI ; Hyewon PARK ; Hyelim PARK ; Dasom MUN ; Hyo Eun KIM ; Nuri YUN ; Boyoung JOUNG
International Journal of Arrhythmia 2017;18(2):77-84
BACKGROUND: The Htr3a antagonist, ondansetron, has been reported to prolong the QT interval and induce Torsades de pointes in the treatment of postoperative nausea and vomiting. To explore the mechanisms underlying these findings, we examined the effects of ondansetron on the mouse cardiac voltage-gated K⁺ (Kv) channel. METHODS AND RESULTS: Ondansetron increased QT intervals in late pregnant (LP) mice. We measured the Kv channels in freshly isolated left ventricular (LV) myocytes from non-pregnant (NP) and late pregnant (LP) mice, using patch-clamp electrophysiology. Ondansetron blocked Kv current at a dose of 50 µM, and reduced the amplitude of peak current densities in a dose-dependent manner (0, 1, 5, 50 µM), in LP but not in NP mice. In contrast, serotonin and the Htr3 agonist, m-CPBG, increased Kv current densities in NP, but not in LP mice. Interestingly, during pregnancy, serum serotonin levels were markedly increased, suggesting the saturation of the effect of serotonin. Immunostaning data showed that Kv4.3 protein and Htr3a co-localize at the membrane and t-tubule of cardiomyocytes. Moreover, Kv4.3 membrane trafficking was enhanced in response to Htr3a-mediated serotonin stimulation in NP, but not in LP mice. Membrane analysis showed that serotonin enhances Kv4.3 membrane trafficking in NP, but not LP mice. CONCLUSION: Ondansetron reduced Kv current densities, and reduced the Kv4.3 membrane trafficking in LP mouse ventricular cardiomyocytes. This data suggests that QT prolongation by ondansetron is mediated by the reduction of Kv current densities and Kv4.3 membrane trafficking.
Animals
;
Electrophysiology
;
Membranes
;
Mice*
;
Muscle Cells*
;
Myocytes, Cardiac
;
Ondansetron*
;
Postoperative Nausea and Vomiting
;
Pregnancy
;
Serotonin
;
Torsades de Pointes
5.Intraoperative management of critical arrhythmia.
Chang Hee KWON ; Seong Hyop KIM
Korean Journal of Anesthesiology 2017;70(2):120-126
The incidence of intraoperative arrhythmia is extremely high, and some arrhythmias require clinical attention. Therefore, it is essential for the anesthesiologist to evaluate risk factors for arrhythmia and understand their etiology, electrophysiology, diagnosis, and treatment. Anesthetic agents reportedly affect normal cardiac electrical activity. In the normal cardiac cycle, the sinoatrial node initiates cardiac electrical activity through intrinsic autonomous pacemaker activity. Sequential atrial and ventricular contractions result in an effective cardiac pumping mechanism. Arrhythmia occurs due to various causes, and the cardiac pumping mechanism may be affected. A severe case may result in hemodynamic instability. In this situation, the anesthesiologist should eliminate the possible causes of arrhythmia and manage the condition, creating hemodynamic stability under proper electrocardiographic monitoring.
Anesthesia
;
Anesthetics
;
Arrhythmias, Cardiac*
;
Diagnosis
;
Electrocardiography
;
Electrophysiology
;
Hemodynamics
;
Incidence
;
Risk Factors
;
Sinoatrial Node
6.Meta-analysis on risk stratification of malignant ventricular tachyarrhythmic events in arrhythmogenic right ventricular cardiomyopathy
Young Eun ROH ; Hyun Ji JANG ; Min Jung CHO
Yeungnam University Journal of Medicine 2017;34(2):208-215
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy characterized by predominant right ventricular fibro-fatty replacement, right ventricular dysfunction and ventricular arrhythmias. It is a rare but important cause of sudden cardiac death in children and young adults. A meta-analysis on risk stratification of major ventricular tachyarrhythmic events indicating the need for implantable cardioverter defibrillator therapy in ARVC was performed.METHODS: The pubmed database was searched from its inception to May 2015. Of the 433 citations identified, 12 were included in this meta-analysis. Data regarding major ventricular tachyarrhythmic events were retrieved in 817 subjects from the studies. For the variables, a combined odds ratio (OR) was calculated using a fixed-effects meta-analysis.RESULTS: Extensive right ventricular dysfunction (OR, 2.44), ventricular late potential (OR, 1.66), inducible ventricular tachyarrhythmia during electrophysiology study (OR, 3.67), non-sustained ventricular tachycardia (OR, 3.78), and history of fatal event/sustained VT (OR, 5.66) identified as significant risk factors (p < 0.0001).CONCLUSION: This meta-analysis shows that extensive right ventricular dysfunction, ventricular late potential, inducible ventricular tachyarrhythmia during electrophysiological study, non-sustained ventricular tachycardia, and history of sustained ventricular tachycardia/fibrillation are consistently reported risk factors of major ventricular tachyarrhythmic events indicating implantable cardioverter defibrillator therapy in patients with ARVC.
Arrhythmias, Cardiac
;
Arrhythmogenic Right Ventricular Dysplasia
;
Cardiomyopathies
;
Child
;
Death, Sudden
;
Death, Sudden, Cardiac
;
Defibrillators
;
Electrophysiology
;
Humans
;
Odds Ratio
;
Risk Factors
;
Tachycardia
;
Tachycardia, Ventricular
;
Ventricular Dysfunction, Right
;
Young Adult
7.Non Sinus Focal Atrial Tachycardia.
International Journal of Arrhythmia 2016;17(4):210-213
Non sinus focal atrial tachycardia (AT) is an uncommon arrhythmia. Electrocardiograms (ECGs) can be used to diagnose the condition. ECGs can also be used to pinpoint the origin of the focal AT; however, the precise location is ultimately confirmed by electrophysiology. Automaticity, triggered activity, and micro-reentry are possible underlying mechanisms for focal AT. Pharmacological therapy is recommended for symptomatic patients. Radiofrequency catheter ablation is a viable alternative, especially in patients intolerant to drugs, or patients with drug-refractory focal AT. This review describes the epidemiology, clinical features, diagnosis, and mechanisms of focal AT, as well as possible therapeutic approaches for this condition.
Arrhythmias, Cardiac
;
Catheter Ablation
;
Diagnosis
;
Electrocardiography
;
Electrophysiology
;
Epidemiology
;
Humans
;
Tachycardia*
;
Tachycardia, Ectopic Atrial
8.Optimized Fluoroscopy Setting and Appropriate Project Position Can Reduce X-ray Radiation Doses Rates during Electrophysiology Procedures.
Bing-Bo HOU ; Yan YAO ; Ling-Min WU ; Yu QIAO ; Li-Hui ZHENG ; Li-Gang DING ; Gang CHEN ; Shu ZHANG
Chinese Medical Journal 2015;128(9):1151-1153
BACKGROUNDNonfluoroscopic three-dimensional electroanatomical system is widely used nowadays, but X-ray remains indispensable for complex electrophysiology procedures. This study aimed to evaluate the value of optimized parameter setting and different projection position to reduce X-ray radiation dose rates.
METHODSFrom June 2013 to October 2013, 105 consecutive patients who underwent complex ablation were enrolled in the study. After the ablation, the radiation dose rates were measured by two different settings (default setting and optimized setting) with three projection positions (posteroanterior [PA] projection; left anterior oblique [LAO] 30° projection; and LAO 45° projection). The parameter of preset voltage, pulse width, critical voltage, peak voltage, noise reduction, edge enhancement, pulse rate, and dose per frame was modified in the optimized setting.
RESULTSThe optimized setting reduced radiation dose rates by 87.5% (1.7 Gy/min vs. 13.6 Gy/min, P < 0.001) in PA, 87.3% (2.5 Gy/min vs. 19.7 Gy/min, P < 0.001) in LAO 30°, 85.9% (3.1 Gy/min vs. 22.1 Gy/min, P < 0.001) in LAO 45°. Increase the angle of projection position will increase the radiation dose rate.
CONCLUSIONSWe can reduce X-ray radiation dose rates by adjusting the parameter setting of X-ray system. Avoiding oblique projection of large angle is another way to reduce X-ray radiation dose rates.
Adult ; Aged ; Arrhythmias, Cardiac ; surgery ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Electrophysiology ; Female ; Fluoroscopy ; methods ; Humans ; Male ; Middle Aged ; Radiation Dosage
9.Initial experience of subcutaneous implantable cardioverter defibrillators in Singapore: a case series and review of the literature.
Tien Siang Eric LIM ; Boon Yew TAN ; Kah Leng HO ; Chuh Yih Paul LIM ; Wee Siong TEO ; Chi-Keong CHING
Singapore medical journal 2015;56(10):580-585
Transvenous implantable cardioverter defibrillators are a type of implantable cardiac device. They are effective at reducing total and arrhythmic mortality in patients at risk of sudden cardiac death. Subcutaneous implantable cardioverter defibrillators (S-ICDs) are a new alternative that avoids the disadvantages of transvenous lead placement. In this case series, we report on the initial feasibility and safety of S-ICD implantation in Singapore.
Adult
;
Death, Sudden, Cardiac
;
prevention & control
;
Defibrillators, Implantable
;
statistics & numerical data
;
Electrophysiology
;
Follow-Up Studies
;
Humans
;
Male
;
Middle Aged
;
Patient Safety
;
Prosthesis Implantation
;
Singapore
;
Tachycardia, Ventricular
;
Ventricular Fibrillation
10.Effect of bronchoalveolar lavage on the heart rhythm and conduction of the children with severe pneumonia.
Chinese Journal of Pediatrics 2014;52(4):252-256
OBJECTIVETo observe the effect of bronchoalveolar lavage on the heart rhythm and conduction of children with severe pneumonia through monitoring the electrocardiogram change of different step of the bronchoalveolar lavage, for proving the safety of the operation of bronchoalveolar lavage from the perspective of cardiac electrophysiology.
METHODFrom July 2011 to March 2012, 30 patients who were hospitalized in pneumology department of Dalian Children's Hospital and met the inclusion criteria and therapeutic indications of bronchoalveolar lavage were chosen. They were 3 to 12 years old, the average age was 5.3 years, including 17 boys and 13 girls, the ratio of boys and girls is 1.3: 1. Continuous sampling the electrocardiogram before and during the process including anesthesia, entering into glottis, lavage, aspiration, and revive, and recording the heart rate, rhythm amplitude and width of P wave, the PR interval, the form and width of QRS complex were also measured. The recorded data were analyzed and statistical analysis to reflect the change of the cardiac electrophysiology.
RESULTThe incidence of heart rate increase was 100.0%, 26 (86.7%) patients began to emerge after anesthesia, the rest of the patients also developed heart rate increase after the start of bronchoscopic operation. All patients had sinus tachycardia, and were most obvious in the progress of lavage and revive. In the process of entering into glottis, lavage, aspiration, 13 (43.3%) patients had arrhythmia episodes. Types of arrhythmia included sinus bradycardia, atrioventricular block and premature beat. Incidences of intraoperative arrhythmia compared with the pre- and post-operation were all statistically significantly different (P = 0.00). The most common arrhythmia were premature beat, in 17 of the 30 cases there were premature beat including 9 cases with atrial premature beats and 8 cases ventricular premature contraction. Two patients had III° atrioventricular block accompanied by serious sinus bradycardia. All kinds of arrhythmias except sinus tachycardia disappeared after the operation was ended. Five patients (16.7%) had PR interval prolongation. Five patients (16.7%) had incomplete right bundle branch block (IRBBB) . Incidences of IRBBB compared with the pre-operation and post-operation were all not significantly different [13.3% (n = 4) vs. 0(n = 0) and 3.3% (n = 1), all P > 0.05]. Different operating progress made no significant difference in the measurement value of electrocardiogram[13.3% (n = 4) vs. 0(n = 0) and 3.3% (n = 1), all P > 0.05], but showed the most notable effect on heart rate.
CONCLUSIONBronchoalveolar lavage can influence the heart rhythm and conduction, but most of the influence with pathological significance are transient. Cardiac electrophysiological changes were the most obvious in endotracheal operation with the risk of malignant arrhythmia but the risk is low, the bronchoalveolar lavage technique is safe. The contingency plans for dealing with all kinds of adverse reactions must be ready before the operations of bronchoalveolar lavage. During the procedure, the patient's ECG changes should be closely monitored to reduce the incidence of adverse reactions.
Arrhythmias, Cardiac ; etiology ; physiopathology ; Bronchoalveolar Lavage ; adverse effects ; methods ; Bronchoscopy ; adverse effects ; methods ; Cardiac Complexes, Premature ; etiology ; physiopathology ; Cardiac Electrophysiology ; Child ; Child, Preschool ; Electrocardiography ; Female ; Heart Block ; etiology ; physiopathology ; Heart Rate ; physiology ; Humans ; Hypoxia ; etiology ; physiopathology ; Male ; Pneumonia ; pathology ; therapy

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