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Tsumoto K, Shimamoto T, Aoji Y, Himeno Y, Kuda Y, Tanida M, Amano A, Kurata Y. Chained occurrences of early afterdepolarizations may create a directional triggered activity to initiate reentrant ventricular tachyarrhythmias. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2025; 261:108587. [PMID: 39837062 DOI: 10.1016/j.cmpb.2025.108587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 11/29/2024] [Accepted: 01/03/2025] [Indexed: 01/23/2025]
Abstract
BACKGROUND AND OBJECTIVE It has been believed that polymorphic ventricular tachycardia (VT) such as torsades de pointes (TdP) seen in patients with long QT syndromes is triggered by creating early afterdepolarization (EAD)-mediated triggered activity (TA). Although the mechanisms creating the TA have been studied intensively, characteristics of the arrhythmogenic (torsadogenic) substrates that link EAD developments to TA formation are still not well understood. METHODS Computer simulations of excitation propagation in a homogenous two-dimensional ventricular tissue with an anisotropic conduction property were performed to characterize torsadogenic substrates that potentially form TA. We examined how the configuration of islands (clusters) of myocytes with synchronously chained occurrence of EADs within the tissue, each EAD cluster size and stimulation from different directions impact the TA creation. RESULTS The presence of EAD clusters within the tissue created local regions of cardiomyocytes maintained at a depolarized membrane potential above 0 mV due to the chained occurrence of EADs. When the local area contained a concave surface border, the TA was created depending on its curvature. We found that the distance of EAD clusters was a critical factor for the development of EAD-mediated TA and polymorphic VT in long QT syndromes, that there existed a region of the distance favorable for the development of TA and VT, and that the TA was always created along the myocardial fiber orientation regardless of stimulating directions. CONCLUSION The chained occurrences of EADs may create a directional TA. Our findings provide deeper understandings of the cardiac arrhythmogenic substrates for preventing and treating arrhythmias.
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Affiliation(s)
- Kunichika Tsumoto
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan.
| | - Takao Shimamoto
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yuma Aoji
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yukiko Himeno
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yuhichi Kuda
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Mamoru Tanida
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Akira Amano
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yasutaka Kurata
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan.
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Zhang ZH, Barajas-Martinez H, Duan HY, Fan GH, Jiang H, Antzelevitch C, Xia H, Hu D. Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8. Front Cardiovasc Med 2025; 12:1546803. [PMID: 40182425 PMCID: PMC11965590 DOI: 10.3389/fcvm.2025.1546803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/07/2025] [Indexed: 04/05/2025] Open
Abstract
Background Previous studies suggested that SCN10A/Nav1.8 may influence cardiac electrophysiology and the susceptibility to cardiac arrhythmias. Notably, the expression of SCN10A is not uniform, showing variable expression in each cardiac chamber. The present study aims to explore the functional significance of Nav1.8 expression among different cell types present in the ventricular myocardium. Methods The effect of the specific Nav1.8 blocker, A-803467, on action potential was recorded from epicardial, mid-myocardial (M cells) and Purkinje tissue slices isolated from the canine left ventricle using standard microelectrode techniques and on late sodium current from Purkinje cells using patch-clamp techniques. Results A-803467 treatment did not significantly affect maximum diastolic potential, action potential amplitude or maximum rate of rise of the action potential upstroke in epicardial cells, M cells or Purkinje fibers. Action potential duration (APD) was also unaffected by A-803467 in epicardial cells. However, administration of 1,000 nmol/L A-803467 reduced APD30, APD50, and APD90 during relatively slow pacing rates of 0.2 and 0.5 Hz in M cells. In Purkinje fibers, A-803467 (100 and 1,000 nmol/L) substantially abbreviated APD50 and APD90 at slow pacing rates (0.2 and 0.5 Hz). Moreover, 100 nmol/L A-803467 significantly inhibited the development of early afterdepolarizations induced by 10 nmol/L ATX-II (7/8 vs. 2/8, p < 0.05) as well as the amplitude of late sodium current at 0.2 Hz in Purkinje cells. Conclusions The functional significance of Nav1.8 varies among different types of ventricular and conduction system cardiomyocytes. The reduction in INa,L and APD, as well as suppression of early afterdepolarizations by Nav1.8 block in Purkinje fibers suggests Nav1.8 as a potential therapeutic target for bradycardia-dependent arrhythmias.
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Affiliation(s)
- Zhong-He Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Hector Barajas-Martinez
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Department, Lankenau Institute for Medical Research, Lankenau Heart Institute, Wynnwood, PA, United States
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Hong-Yi Duan
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Guo-Hua Fan
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Charles Antzelevitch
- Cardiovascular Research Department, Lankenau Institute for Medical Research, Lankenau Heart Institute, Wynnwood, PA, United States
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Hao Xia
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Dan Hu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan, China
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Takasugi N, Endo S, Takasugi M, Tochibora R, Yoshida A, Watanabe T, Kawaguchi T, Yamada Y, Kanamori H, Ushikoshi H, Okura H. Roles of Atrial Arrhythmias in Triggering Torsade de Pointes in Patients With Acquired Long QT Syndrome. Circ Arrhythm Electrophysiol 2024; 17:e012675. [PMID: 39234741 DOI: 10.1161/circep.123.012675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 08/13/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND Little is known about the role of atrial arrhythmias (AAs) in triggering Torsade de Pointes (TdP) in patients with long QT syndrome (LQTS). The aim of this study was to examine the contribution of AAs to the development of TdP in acquired LQTS patients. METHODS The initiation patterns of 81 episodes of TdP obtained from 34 consecutive acute acquired LQTS patients (14 men, median age, 69 years; median QTc, 645.5 ms) with documented TdP were analyzed. The initiation mode of TdP was divided into 3 categories: (1) preceding short-long sequence (SLS); (2) sudden R-on-T phenomenon without preceding SLS; and (3) increased atrial rate. The patients were divided into 2 groups based on the presence or absence of AAs-induced TdP; AAs-induced (n=18) and non-AAs-induced (n=16) groups. The association of clinical/ECG characteristics and TdP frequency after initiating conventional therapy with AAs-induced TdP was evaluated. The groups were compared using the Mann-Whitney U test or Fisher exact test. RESULTS AAs-induced group comprised 52.9% (18/34) of the patients studied. TdP was preceded by AAs-initiated SLSs in 41.2% (14/34) of the patients and was directly induced by R-on-T AAs (AAs coincidentally encountered a vulnerable repolarizing region during the T wave) in 23.5% (8/34). AAs triggered 48 (59.3%) of the 81 TdP episodes. AAs initiated SLSs in 67.8% (40/59) of the SLS-induced TdP episodes. R-on-T AAs accounted for 23.5% (19/81) of the TdP episodes. AAs-induced group experienced TdP after initiating therapy more frequently than non-AAs-induced group (2.5 versus 1 event, P=0.008). AAs-induced group exhibited macroscopic T-wave alternans more frequently than non-AAs-induced group (6 versus 0 event, P=0.02). CONCLUSIONS AAs play a key role in triggering TdP in more than half of patients with acute acquired LQTS and can increase TdP frequency after initiating therapy. Thus, AAs are not benign but rather can be life-threatening in patients with acute acquired LQTS.
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Affiliation(s)
- Nobuhiro Takasugi
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Susumu Endo
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | | | - Ryota Tochibora
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Akihiro Yoshida
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Takatomo Watanabe
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Tomonori Kawaguchi
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Yoshihisa Yamada
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Hiromitsu Kanamori
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Hiroaki Ushikoshi
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
| | - Hiroyuki Okura
- Gifu University Hospital (N.T., S.E., R.T., A.Y., T.W., T.K., Y.Y., H.K., H.U., H.O.)
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Tsukada S, Iwasaki YK, Tsukada YT. Tensor cardiography: A novel ECG analysis of deviations in collective myocardial action potential transitions based on point processes and cumulative distribution functions. PLOS DIGITAL HEALTH 2024; 3:e0000273. [PMID: 39116062 PMCID: PMC11309480 DOI: 10.1371/journal.pdig.0000273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 06/17/2024] [Indexed: 08/10/2024]
Abstract
To improve clinical diagnoses, assessments of potential cardiac disease risk, and predictions of lethal arrhythmias, the analysis of electrocardiograms (ECGs) requires a more accurate method of weighting waveforms to efficiently detect abnormalities that appear as minute strains in the waveforms. In addition, the inverse problem of estimating the myocardial action potential from the ECG has been a longstanding challenge. To analyze the variance of the ECG waveforms and to estimate collective myocardial action potentials (APs) from the ECG, we designed a model equation incorporating the probability densities of Gaussian functions of time-series point processes in the cardiac cycle and dipoles of the collective APs in the myocardium. The equation, which involves taking the difference between the cumulative distribution functions (CDFs) that represent positive endocardial and negative epicardial potentials, fits both R and T waves. The mean, standard deviation, weights, and level of each cumulative distribution function (CDF) are metrics for the variance of the transition state of the collective myocardial AP. Clinical ECGs of myocardial ischemia during coronary intervention show abnormalities in the aforementioned specific elements of the tensor associated with repolarization transition variance earlier than in conventional indicators of ischemia. The tensor can be used to evaluate the beat-to-beat dynamic repolarization changes between the ventricular epi and endocardium in terms of the Mahalanobis distance (MD). This tensor-based cardiography that uses the differences between CDFs to show changes in collective myocardial APs has the potential to be a new analysis tool for ECGs.
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Affiliation(s)
- Shingo Tsukada
- Molecular and Bio Science Research Group, NTT Basic Research Laboratories and Bio-Medical Informatics Research Center, 3–1, Morinosato Wakamiya, Atsugi-city, Kanagawa Pref., Japan Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Japan
| | - Yu-ki Iwasaki
- Department of Cardiovascular Medicine, Nippon Medical School, Japan
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Tsumoto K, Shimamoto T, Aoji Y, Himeno Y, Kuda Y, Tanida M, Amano A, Kurata Y. Theoretical prediction of early afterdepolarization-evoked triggered activity formation initiating ventricular reentrant arrhythmias. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2023; 240:107722. [PMID: 37515880 DOI: 10.1016/j.cmpb.2023.107722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 07/02/2023] [Accepted: 07/14/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND AND OBJECTIVE Excessive prolongation of QT interval on ECGs in patients with congenital/acquired long QT syndrome and heart failure is a sign suggesting the development of early afterdepolarization (EAD), an abnormal repolarization in the action potential of ventricular cardiomyocytes. The development of EAD has been believed to be a trigger for fatal tachyarrhythmia, which can be a risk for sudden cardiac death. The role of EAD in triggering ventricular tachycardia (VT) remains unclear. The aim of this study was to elucidate the mechanism of EAD-induced triggered activity formation that leads to the VT such as Torsades de Pointes. METHODS We investigated the relationship between EAD and tachyarrhythmia initiation by constructing homogeneous myocardial sheet models consisting of the mid-myocardial cell version of a human ventricular myocyte model and performing simulations of excitation propagation. RESULTS A solitary island-like (clustering) occurrence of EADs in the homogeneous myocardial sheet could induce a focal excitation wave. However, reentrant excitation, an entity of tachyarrhythmia, was not able to be triggered regardless of the EAD cluster size when the focal excitation wave formed a repolarization potential difference boundary consisting of only a convex surface. The discontinuous distribution of multiple EAD clusters in the ventricular tissue formed a specific repolarization heterogeneity due to the repolarization potential difference, the shape of which depended on EAD cluster size and placed intervals. We found that the triggered activity was formed in such a manner that the repolarization potential difference boundary included a concave surface. CONCLUSIONS The formation of triggered activity that led to tachyarrhythmia required not only the occurrence of EAD onset-mediated focal excitation wave but also a repolarization heterogeneity-based specific repolarization potential difference boundary shape formed within the tissue.
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Affiliation(s)
- Kunichika Tsumoto
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan.
| | - Takao Shimamoto
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yuma Aoji
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yukiko Himeno
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yuhichi Kuda
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Mamoru Tanida
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Akira Amano
- Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
| | - Yasutaka Kurata
- Department of Physiology II, Kanazawa Medical University, Uchinada 920-0293, Japan.
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Takeguchi M, Kusumoto S, Sekiguchi K, Suenobu S, Ihara K. Predicting Long-Term Ventricular Arrhythmia Risk in Children with Acute Lymphoblastic Leukemia Using Normal Values of Ventricular Repolarization Markers Established from Japanese Cohort Study. J Clin Med 2023; 12:4723. [PMID: 37510838 PMCID: PMC10381239 DOI: 10.3390/jcm12144723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/12/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Cardiac complications due to anthracycline treatment may become evident several years after chemotherapy and are recognized as a serious cause of morbidity and mortality in cancer patients or childhood cancer survivors. OBJECTIVES We analyzed ventricular repolarization parameters in electrocardiography for pediatric acute lymphoblastic leukemia patients during chemotherapy and in long-term follow-up. To establish the reference values of ventricular repolarization parameters in children, we retrospectively summarized the Tpe interval, QT interval, QTc interval, and Tpe/QT ratio in healthy Japanese children. METHODS Electrocardiography data recorded from students in 1st and 7th grades were randomly selected from a database maintained by the school-based screening system in the Oita city cohort, Japan. Subsequently, chronological data of the Tpe/QT ratio in 17 pediatric patients with acute lymphoblastic leukemia were analyzed over time. RESULTS The mean ± standard deviation of the Tpe interval in 1st and 7th graders was 70 ± 7 and 78 ± 17 ms, respectively, while the mean ± standard deviation of the Tpe/QT ratio was 0.21 ± 0.02 and 0.22 ± 0.02 ms, respectively. During the intensive phase of treatment, the Tpe/QT ratios of 3 high-risk patients among the 17 patients with acute lymphoblastic leukemia exceeded the upper limit. CONCLUSION The Tpe/QT ratio has a potential clinical application in predicting the risk of long-term ventricular arrhythmia of cancer patients or childhood cancer survivors from childhood to adulthood.
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Affiliation(s)
- Masahiro Takeguchi
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu 879-5593, Oita, Japan
| | - Satoshi Kusumoto
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu 879-5593, Oita, Japan
| | - Kazuhito Sekiguchi
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu 879-5593, Oita, Japan
| | - Souichi Suenobu
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu 879-5593, Oita, Japan
| | - Kenji Ihara
- Department of Pediatrics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu 879-5593, Oita, Japan
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Duca ȘT, Roca M, Costache AD, Chetran A, Afrăsânie I, Miftode RȘ, Tudorancea I, Matei I, Ciorap RG, Mitu O, Bădescu MC, Iliescu-Halitchi D, Halițchi-Iliescu CO, Mitu F, Lionte C, Costache II. T-Wave Analysis on the 24 h Holter ECG Monitoring as a Predictive Assessment of Major Adverse Cardiovascular Events in Patients with Myocardial Infarction: A Literature Review and Future Perspectives. Life (Basel) 2023; 13:life13051155. [PMID: 37240799 DOI: 10.3390/life13051155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 05/01/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.
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Affiliation(s)
- Ștefania-Teodora Duca
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Mihai Roca
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Alexandru-Dan Costache
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Adriana Chetran
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Irina Afrăsânie
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Radu-Ștefan Miftode
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Ionuț Tudorancea
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
- Department of Morpho-Functional Science II-Physiology, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
| | - Iulian Matei
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Radu-George Ciorap
- Department of Biomedical Science, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa", 700145 Iasi, Romania
| | - Ovidiu Mitu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Minerva Codruța Bădescu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of III Internal Medicine Clinic, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Dan Iliescu-Halitchi
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, Arcadia Hospital, 700620 Iasi, Romania
| | - Codruța-Olimpiada Halițchi-Iliescu
- Department of Mother and Child Medicine-Pediatrics, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Pedriatics, Arcadia Hospital, 700620 Iasi, Romania
| | - Florin Mitu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Cătălina Lionte
- Department of Internal Medicine III, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700145 Iasi, Romania
- Department of Cardiology, Helicomed Hospital, 700115 Iasi, Romania
| | - Irina-Iuliana Costache
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
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Kihlgren M, Almqvist C, Amankhani F, Jonasson L, Norman C, Perez M, Ebrahimi A, Gottfridsson C. The U-wave: A remaining enigma of the electrocardiogram. J Electrocardiol 2023; 79:13-20. [PMID: 36907158 DOI: 10.1016/j.jelectrocard.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/07/2023]
Abstract
The U-wave's electrophysiological origin remains unknown and is subject to debate. It is rarely used for diagnosis in clinical practice. The aim of this study was to review new information regarding the U-wave. Further to present the proposed theories behind the U-wave's origin along with potential pathophysiologic and prognostic implications related to its presence, polarity and morphology. METHOD Literature searches were conducted to retrieve publications related to the electrocardiogram U-wave in the literature database Embase. RESULTS The review of the literature revealed the following major theories that will be discussed; late depolarisation, delayed or prolonged repolarisation, electro-mechanical stretch and IK1 dependent intrinsic potential differences in the terminal part of the action potential. Various pathologic conditions were found to correlate with the presence and properties of the U-wave, such as its amplitude and polarity. Abnormal U-waves can, for example, be observed in coronary artery disease with ongoing myocardial ischemia or infarction, ventricular hypertrophy, congenital heart disease, primary cardiomyopathy and valvular defects. Negative U-waves are highly specific for the presence of heart diseases. Concordantly negative T- and U-waves are especially associated with cardiac disease. Patients with negative U-waves tend to have higher blood pressure and history of hypertension, higher heart rate, cardiac disease and left ventricular hypertrophy compared to subjects with normal U-waves. Negative U-waves have been found to be associated with increased risk of all-cause mortality, cardiac death and cardiac hospitalisation in men. CONCLUSIONS The origin of the U-wave is still not established. U-wave diagnostics may reveal cardiac disorders and the cardiovascular prognosis. Including the U-wave characteristics in the clinical ECG assessment may be useful.
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Affiliation(s)
- Moa Kihlgren
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Christina Almqvist
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Fereydoun Amankhani
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Linda Jonasson
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Cecilia Norman
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Marcos Perez
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Ahmad Ebrahimi
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
| | - Christer Gottfridsson
- Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, Oncology R&D, AstraZeneca Gothenburg, Sweden.
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Ozgul U, Turan OE, Baskurt AA, Yilancioglu RY, Dogdus M, Inevi UD, Ozcan EE. The predictive value of electrocardiographic polarization parameters on appropriate ICD shock in primary prevention heart failure patients. J Electrocardiol 2023; 77:80-84. [PMID: 36347655 DOI: 10.1016/j.jelectrocard.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 11/08/2022]
Abstract
OBJECT The effect of frontal QRS-T angle, Tp-e and Tp-e/QT ratio on cardiac events have been shown in many studies. In this study, we aimed to determine the prognostic value of frontal QRS-T angle, TPe and Tp-e/QT ratio on ICD shock in patients who had ICD (Implantable Cardioverter Defibrillator) implanted due to heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHOD 158 patients with HFrEF who had previous ICD implantation were retrospectively analyzed. 27 patients were found to have an appropriate shock. Frontal QRS-T angle, Tp-e interval, Tp-e/QT ratio were calculated by evaluating the basal ECG records of the patients. Comparisons of these arrhythmogenic predictors were made in patients with and without ICD shock at follow-up. RESULT When 158 patients with previous ICD implantation were analyzed in two groups with and without ICD shock, the number of patients with frontal QRS-T angle >120°, Tp-e interval > 105 ms, Tp-e/QT > 0.2 in the shock group (n: 27) was found to be high with a different significance (p:<0.01, p:<0.01, p:<0.01). There was no significant difference between the two groups regarding other ECG parameters such as QRS duration, QT interval, PR interval, fragmented QRS and positive T wave. In addition, more amiodarone use was observed in the shock group, and more hyperlipidemia cases were observed in the non-shocked group (p:0.01; p:<0.01). CONCLUSION Increased frontal QRS-T angle, Tp-e interval, and Tp-e/QT ratio are arrhythmogenic parameters and predict appropriate ICD shock.
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Affiliation(s)
- Ufuk Ozgul
- Aydin Ataturk State Hospital, Department of Cardiology, Aydin, Turkey.
| | - Oguzhan Ekrem Turan
- Dokuz Eylul University, Faculty of Medicine, Heart Rhythm Management Center, Izmir, Turkey
| | - Ahmet Anil Baskurt
- Dokuz Eylul University, Faculty of Medicine, Department of Cardiology, Izmir, Turkey
| | | | - Mustafa Dogdus
- Usak University, Training and Research Hospital, Department of Cardiology, Usak, Turkey
| | | | - Emin Evren Ozcan
- Dokuz Eylul University, Faculty of Medicine, Heart Rhythm Management Center, Izmir, Turkey
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10
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Saadeh K, Nantha Kumar N, Fazmin IT, Edling CE, Jeevaratnam K. Anti-malarial drugs: Mechanisms underlying their proarrhythmic effects. Br J Pharmacol 2022; 179:5237-5258. [PMID: 36165125 PMCID: PMC9828855 DOI: 10.1111/bph.15959] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/06/2022] [Accepted: 04/28/2022] [Indexed: 01/12/2023] Open
Abstract
Malaria remains the leading cause of parasitic death in the world. Artemisinin resistance is an emerging threat indicating an imminent need for novel combination therapy. Given the key role of mass drug administration, it is pivotal that the safety of anti-malarial drugs is investigated thoroughly prior to widespread use. Cardiotoxicity, most prominently arrhythmic risk, has been a concern for anti-malarial drugs. We clarify the likely underlying mechanisms by which anti-malarial drugs predispose to arrhythmias. These relate to disruption of (1) action potential upstroke due to effects on the sodium currents, (2) action potential repolarisation due to effects on the potassium currents, (3) cellular calcium homeostasis, (4) mitochondrial function and reactive oxygen species production and (5) cardiac fibrosis. Together, these alterations promote arrhythmic triggers and substrates. Understanding these mechanisms is essential to assess the safety of these drugs, stratify patients based on arrhythmic risk and guide future anti-malarial drug development.
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Affiliation(s)
- Khalil Saadeh
- Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK,School of Clinical Medicine, Addenbrooke's HospitalUniversity of CambridgeCambridgeUK
| | | | - Ibrahim Talal Fazmin
- Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK,School of Clinical Medicine, Addenbrooke's HospitalUniversity of CambridgeCambridgeUK
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11
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Oknińska M, Mączewski M, Mackiewicz U. Ventricular arrhythmias in acute myocardial ischaemia-Focus on the ageing and sex. Ageing Res Rev 2022; 81:101722. [PMID: 36038114 DOI: 10.1016/j.arr.2022.101722] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 08/17/2022] [Accepted: 08/20/2022] [Indexed: 01/31/2023]
Abstract
Annually, approximately 17 million people die from cardiovascular diseases worldwide, half of them suddenly. The most common direct cause of sudden cardiac death is ventricular arrhythmia triggered by an acute coronary syndrome (ACS). The study summarizes the knowledge of the mechanisms of arrhythmia onset during ACS in humans and in animal models and factors that may influence the susceptibility to life-threatening arrhythmias during ACS with particular focus on the age and sex. The real impact of age and sex on the arrhythmic susceptibility within the setting of acute ischaemia is masked by the fact that ACSs result from coronary artery disease appearing with age much earlier among men than among women. However, results of researches show that in ageing process changes with potential pro-arrhythmic significance, such as increased fibrosis, cardiomyocyte hypertrophy, decrease number of gap junction channels, disturbances of the intracellular Ca2+ signalling or changes in electrophysiological parameters, occur independently of the development of cardiovascular diseases and are more severe in male individuals. A review of the literature also indicates a marked paucity of research in this area in female and elderly individuals. Greater awareness of sex differences in the aging process could help in the development of personalized prevention methods targeting potential pro-arrhythmic factors in patients of both sexes to reduce mortality during the acute phase of myocardial infarction. This is especially important in an era of aging populations in which women will predominate due to their longer lifespan.
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Affiliation(s)
- Marta Oknińska
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
| | - Michał Mączewski
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
| | - Urszula Mackiewicz
- Department of Clinical Physiology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland.
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12
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Kandzia T, Markiewicz-Łoskot G, Binkiewicz P. Tpeak-Tend Interval during Pregnancy and Postpartum. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:12638. [PMID: 36231942 PMCID: PMC9566342 DOI: 10.3390/ijerph191912638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/21/2022] [Accepted: 09/26/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Pregnancy is a condition in which new cardiac arrhythmias can occur or prior undiagnosed arrhythmias may provide symptoms. The occurrence of severe ventricular arrhythmias and polymorphic ventricular tachycardia that may lead to fainting or sudden cardiac death is promoted by the prolongation of the QTc interval. The post-partum adaptation period is the most arrhythmogenic. TpTe (Tpeak-Tend interval) is a novel marker of arrhythmogenesis by many considered a more sensitive marker than QTc. OBJECTIVE The aim of our work was to determine the TpTe interval (Tpeak-Tend) in women in the first, second and third trimester of pregnancy and the post-partum period. MATERIALS AND METHODS The study group consisted of 128 women in pregnancy or postpartum and a control group of 32 non-pregnant women. A standard 12-lead ECG (electrocardiograph) recording with evaluation of the duration of TpTe and QTc was performed in all patients. RESULTS In comparison to the non-pregnant women, higher values of QTc and TpTe were observed starting in the first trimester with highest values observed in the postpartum period. Mean duration of TpTe interval during pregnancy (81.59 ± 5.92 ms) and in the whole study group (pregnancy + postpartum) (85.46 ± 6.45 ms) was significantly longer (p < 0.001) compared to the TpTe interval in the control group (74.06 ± 6.14 ms). During pregnancy and postpartum, the increase in the TpTe interval in comparison to the increase in the QTc parameter (31.10% vs. 4.18%) was significantly higher (p < 0.001). CONCLUSIONS The study showed an increase in the duration of the TpTe interval and QTc parameter during pregnancy and postpartum with the highest values in the postpartum period. TpTe interval increase was significantly higher compared to QTc increase during pregnancy and postpartum. Changes of TpTe interval were not associated with any clinical outcome or measure of arrythmia burden. Further studies are needed in order to see the clinical significance of these ECG findings, in particular for larger groups of patients with automatic measurement in correlation with echocardiography.
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Affiliation(s)
- Tomasz Kandzia
- Department of Nursing and Social Medical Problems, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Grażyna Markiewicz-Łoskot
- Department of Nursing and Social Medical Problems, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
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13
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Bartolucci C, Forouzandehmehr M, Severi S, Paci M. A Novel In Silico Electromechanical Model of Human Ventricular Cardiomyocyte. Front Physiol 2022; 13:906146. [PMID: 35721558 PMCID: PMC9198403 DOI: 10.3389/fphys.2022.906146] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/10/2022] [Indexed: 11/25/2022] Open
Abstract
Contractility has become one of the main readouts in computational and experimental studies on cardiomyocytes. Following this trend, we propose a novel mathematical model of human ventricular cardiomyocytes electromechanics, BPSLand, by coupling a recent human contractile element to the BPS2020 model of electrophysiology. BPSLand is the result of a hybrid optimization process and it reproduces all the electrophysiology experimental indices captured by its predecessor BPS2020, simultaneously enabling the simulation of realistic human active tension and its potential abnormalities. The transmural heterogeneity in both electrophysiology and contractility departments was simulated consistent with previous computational and in vitro studies. Furthermore, our model could capture delayed afterdepolarizations (DADs), early afterdepolarizations (EADs), and contraction abnormalities in terms of aftercontractions triggered by either drug action or special pacing modes. Finally, we further validated the mechanical results of the model against previous experimental and in silico studies, e.g., the contractility dependence on pacing rate. Adding a new level of applicability to the normative models of human cardiomyocytes, BPSLand represents a robust, fully-human in silico model with promising capabilities for translational cardiology.
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Affiliation(s)
- Chiara Bartolucci
- Computational Physiopathology Unit, Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi", University of Bologna, Bologna, Italy
| | | | - Stefano Severi
- Computational Physiopathology Unit, Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi", University of Bologna, Bologna, Italy
| | - Michelangelo Paci
- BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
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14
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An Automata-Based Cardiac Electrophysiology Simulator to Assess Arrhythmia Inducibility. MATHEMATICS 2022. [DOI: 10.3390/math10081293] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Personalized cardiac electrophysiology simulations have demonstrated great potential to study cardiac arrhythmias and help in therapy planning of radio-frequency ablation. Its application to analyze vulnerability to ventricular tachycardia and sudden cardiac death in infarcted patients has been recently explored. However, the detailed multi-scale biophysical simulations used in these studies are very demanding in terms of memory and computational resources, which prevents their clinical translation. In this work, we present a fast phenomenological system based on cellular automata (CA) to simulate personalized cardiac electrophysiology. The system is trained on biophysical simulations to reproduce cellular and tissue dynamics in healthy and pathological conditions, including action potential restitution, conduction velocity restitution and cell safety factor. We show that a full ventricular simulation can be performed in the order of seconds, emulate the results of a biophysical simulation and reproduce a patient’s ventricular tachycardia in a model that includes a heterogeneous scar region. The system could be used to study the risk of arrhythmia in infarcted patients for a large number of scenarios.
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15
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Gupta A, Pavri BB. Conduction system pacing versus biventricular pacing: Reduced repolarization heterogeneity in addition to improved depolarization. J Cardiovasc Electrophysiol 2021; 33:287-295. [PMID: 34911154 DOI: 10.1111/jce.15329] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/01/2021] [Accepted: 11/15/2021] [Indexed: 11/26/2022]
Abstract
INTRODUCTION His-bundle pacing (HBP) and left-bundle-area pacing (LBAP) are conduction system pacing (CSP) modalities increasingly used as alternatives to conventional biventricular pacing (BiVP). While effects of CSP on ventricular depolarization have been reported, effects on ventricular repolarization have not. METHODS QRS duration (QRSd) and validated ECG parameters of ventricular repolarization associated with arrhythmic risk (T-peak-to-T-endTransmural , T-peak-to-T-endTotal , T-peak dispersion, QTc, QTc dispersion) were analyzed post-implant in 107 patients: 60 with CSP (HBP: n = 35, LBAP: n = 25) and 47 with BiVP. T-wave memory resolution and QTc shortening were analyzed on ECGs obtained ≥25 days post-implant. Twenty blinded measurements were obtained by both authors to assess Interobserver variability. RESULTS Although QRSd was shorter with HBP versus LBAP (119 ± 7 ms vs. 132 ± 9 ms, p = .02), there were no significant differences in any repolarization parameters between these methods of CSP. However, when comparing CSP (HBP + LBAP) to BiVP, both QRSd (125 ± 5 ms vs. 147 ± 7 ms, p < .0001) and repolarization parameters (T-peak-to-T-endTransmural : 83 ± 5 ms vs. 107 ± 8 ms; T-peak-to-T-endTotal : 110 ± 7 ms vs. 137 ± 10 ms; QTc: 470 ± 12 ms vs. 506 ± 12 ms; all p ≤ .0001) were significantly shorter with CSP. Improved T-peak-to-T-end values were unrelated to pre-implant QRSd or LV function. Interobserver variability was 4.6 ± 1.9 ms. Frontal QRS-T angle narrowing (132° to 104°, p = .001) and QTc shortening (483 ± 13 ms to 464 ± 12 ms, p = .008) were seen only with CSP. CONCLUSIONS In addition to improved depolarization, CSP reduced repolarization heterogeneity and provided greater T-wave memory resolution as compared to BiVP. Both modalities of CSP (HBP + LBAP) resulted in comparably reduced repolarization heterogeneity regardless of baseline QRSd and LV function. These observations may confer lower arrhythmogenic risk and warrant further study.
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Affiliation(s)
- Anshul Gupta
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Behzad B Pavri
- Division of Cardiology, Section of Cardiac Electrophysiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
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16
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Kambayashi R, Goto A, Izumi-Nakaseko H, Matsumoto A, Sugiyama A. Measurement of Early and Late Repolarization Periods in Addition to QT Interval to Help Predict the Torsadogenic Risk of Donepezil Based on Reverse Translational Animal Research on Its Proarrhythmic Potential. Circ Rep 2021; 3:555-556. [PMID: 34568635 PMCID: PMC8423611 DOI: 10.1253/circrep.cr-21-0061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 11/12/2022] Open
Affiliation(s)
- Ryuichi Kambayashi
- Department of Pharmacology, Faculty of Medicine, Toho University Tokyo Japan
| | - Ai Goto
- Department of Pharmacology, Faculty of Medicine, Toho University Tokyo Japan
| | | | - Akio Matsumoto
- Department of Aging Pharmacology, Faculty of Medicine, Toho University Tokyo Japan
| | - Atsushi Sugiyama
- Department of Pharmacology, Faculty of Medicine, Toho University Tokyo Japan.,Department of Aging Pharmacology, Faculty of Medicine, Toho University Tokyo Japan
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17
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Kobayashi Y, Nagai T, Takenaka S, Kato Y, Komoriyama H, Nagano N, Kamiya K, Konishi T, Sato T, Omote K, Tsujinaga S, Iwano H, Kusano K, Yasuda S, Ogawa H, Ishibashi-Ueda H, Anzai T. Long-Term Prognostic Significance of Ventricular Repolarization Dispersion in Patients with Cardiac Sarcoidosis. Am J Cardiol 2021; 152:125-131. [PMID: 34127248 DOI: 10.1016/j.amjcard.2021.04.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 10/21/2022]
Abstract
Cardiac sarcoidosis (CS) is frequently complicated by fatal ventricular arrhythmias. T-peak to T-end interval to QT interval ratio (TpTe/QT) on electrocardiograms (ECG) was proposed as a marker of ventricular repolarization dispersion. Although this ratio could be associated with the incidence of ventricular arrhythmias in cardiovascular diseases, its prognostic implication in patients with CS is unclear. We sought to investigate whether TpTe/QT was associated with long-term clinical outcomes in patients with CS. Ninety consecutive patients with CS in 2 tertiary hospitals who had ECG data before initiation of immunosuppressive therapy between November 1995 and March 2019 were examined. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalization, and all-cause death. During a median follow-up period of 4.70 (interquartile range 2.06-7.23) years, the primary outcome occurred in 21 patients (23.3%). Survival analyses revealed that the primary outcome (p < 0.001), especially VT/VF or sudden cardiac death (p = 0.002), occurred more frequently in patients with higher TpTe/QT (≥ 0.242, the median) than in those with lower TpTe/QT. Multivariable Cox regression analysis showed that a higher TpTe/QT was independently associated with increased subsequent risk of adverse events (hazard ratio1.11, 95% confidence interval 1.03-1.20, p = 0.008) even after adjustment for the significant covariates. In conclusion, a higher TpTe/QT was associated with worse long-term clinical outcomes, especially fatal ventricular arrhythmic events, in patients with cardiac sarcoidosis, suggesting the importance of assessing TpTe/QT as a surrogate for risk stratification in these patients.
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18
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Evalution of Tp-E Interval on Electrocardiography Recordings in Elderly Hemodialysis Patients And Its Associations With Electrolyte Imbalances. ANADOLU KLINIĞI TIP BILIMLERI DERGISI 2021. [DOI: 10.21673/anadoluklin.790495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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19
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Karadeniz C. Importance of electrocardiographic markers in predicting cardiac events in children. Biomark Med 2020; 14:1679-1689. [PMID: 33336595 DOI: 10.2217/bmm-2020-0391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
ECG is a common diagnostic tool in medical practice. Sudden cardiac death (SCD) is a rare but devastating event. The most common cause of SCD in the young is a primary arrhythmic event, which is often produced by malignant ventricular arrhythmia. Several electrocardiographic markers for ventricular repolarization and depolarization have been proposed to predict this arrhythmic risk and SCD in children. Although many of these parameters can easily be used in clinical practice, some of them need specific techniques for interpretation. In this review, we summarized the current knowledge regarding the clinical importance and the ability of these ECG parameters to predict adverse cardiac events in the pediatric population.
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Affiliation(s)
- Cem Karadeniz
- Department of Pediatric Cardiology, Pediatric Arrhythmia & Electrophysiology, School of Medicine, Kâtip Celebi University, Izmir, Turkey
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20
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Zhao D, Liang B, Peng J, Tang L, Su R, Luo L, Deng B, Wang S. Tp-e and (Tp-e)/QT ratio as a non-invasive risk factors for malignant ventricular arrhythmia in patients with idiopathic ventricular premature complexes. J Clin Lab Anal 2020; 35:e23636. [PMID: 33332643 PMCID: PMC7891518 DOI: 10.1002/jcla.23636] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 09/03/2020] [Accepted: 09/14/2020] [Indexed: 11/24/2022] Open
Abstract
Background To evaluate the role of Tp‐e and (Tp‐e)/QT ratio in differentiating benign ventricular premature complex (VPC) and malignant polymorphic ventricular tachycardia (PVT). Methods From January 2017 to December 2017, patients with documented polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF) were consecutive included and classified as PVT/VF group. Sixty age‐ and sex‐matched healthy individuals were recruited as comparative control and subdivided into non‐VPC and VPC group. Clinical characteristics and Tp‐e and Tp‐e/QT ratio between the three groups were compared. Results Tp‐e and (Tp‐e)/QT ratio were significantly higher in patients of PVT/VF group compared with the other two groups (P < .001). Episodes of syncope were more frequent in patients with PVT/VF (P < .05). The sensitivity and specificity of a Tp‐e interval ≥86 ms for malignant arrhythmias triggered by VPCs were 88% and 66%, respectively, while the sensitivity and specificity of the Tp‐e/QT ratio ≥0.24 were 82% and 70%, respectively. Five patients complained recurrence of syncope in the PVT/VF group and 1 patient died with mean follow‐up of 18 months. Conclusion Tp‐e interval and the Tp‐Te/QT ratio is significantly increased in patients with PVT/VF and may be used as a novel non‐invasive marker of differentiating malignant and benign VPC.
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Affiliation(s)
- Donghua Zhao
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Bo Liang
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Jian Peng
- Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liangyu Tang
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Rongbin Su
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Lingli Luo
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Bin Deng
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
| | - Shuyuan Wang
- Department of Cardiology, The First People's Hospital of Zhaoqing City, Zhaoqing City, China
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21
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Miki T, Senoo K, Okura T, Shiraishi H, Shirayama T, Aiba T, Matoba S. First episode of ventricular fibrillation in an 84-year-old man with long-QT type 2 syndrome: A case report. J Cardiol Cases 2020; 22:257-259. [PMID: 33304416 PMCID: PMC7718543 DOI: 10.1016/j.jccase.2020.07.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 07/01/2020] [Accepted: 07/07/2020] [Indexed: 11/21/2022] Open
Abstract
Congenital long QT syndrome (LQTS) is associated with ventricular arrhythmia and an increased risk of sudden cardiac death in young people. However, it is extremely rare for an elderly man to experience ventricular fibrillation (VF) due to congenital LQTS as a first episode. We describe the case of an 84-year-old man who experienced syncope after urination. He had a medical history of hypertension and asthma, but no history of syncope. Electrocardiographic findings in 2017 showed QT prolongation (corrected QT = 505 ms). No medication that could induce QT prolongation was administered. Blood test results on admission showed no electrolyte abnormalities, and there were no abnormal findings on echocardiography. The second episode of loss of consciousness occurred during hospitalization, and electrocardiography revealed incessant torsade de pointes, caused by R-on-T with short-long-short (SLS) sequences due to bradyarrhythmia. Coronary angiography did not detect myocardial ischemia, and an implantable cardioverter-defibrillator was implanted for secondary prevention. Genetic testing revealed a mutation of the KCNH2 gene, indicating LQTS type 2. In summary, we report a rare case of prolonged QT interval with SLS sequences due to sick sinus syndrome triggering VF as the first attack in an elderly patient with LQTS type 2. .
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Affiliation(s)
- Tomonori Miki
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Keitaro Senoo
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Cardiac Arrhythmia Research and Innovation, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takashi Okura
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hirokazu Shiraishi
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Cardiac Arrhythmia Research and Innovation, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Shirayama
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Cardiac Arrhythmia Research and Innovation, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Aiba
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Satoaki Matoba
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Cardiac Arrhythmia Research and Innovation, Kyoto Prefectural University of Medicine, Kyoto, Japan
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22
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Meo M, Bonizzi P, Bear LR, Cluitmans M, Abell E, Haïssaguerre M, Bernus O, Dubois R. Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study. Front Physiol 2020; 11:933. [PMID: 32903614 PMCID: PMC7438571 DOI: 10.3389/fphys.2020.00933] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/10/2020] [Indexed: 12/15/2022] Open
Abstract
Background Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model. Methods Langendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (TPEAK-TEND) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites. Results After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components. Conclusion Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.
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Affiliation(s)
- Marianna Meo
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France
| | - Pietro Bonizzi
- Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, Netherlands
| | - Laura R Bear
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France
| | - Matthijs Cluitmans
- Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, Netherlands
| | - Emma Abell
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France
| | - Michel Haïssaguerre
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France.,Bordeaux University Hospital (CHU), Electrophysiology and Ablation Unit, Pessac, France
| | - Olivier Bernus
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France
| | - Rémi Dubois
- Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.,University of Bordeaux, CRCTB, Bordeaux, France.,INSERM, CRCTB, U1045, Bordeaux, France
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23
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Zhou X, Qu Y, Passini E, Bueno-Orovio A, Liu Y, Vargas HM, Rodriguez B. Blinded In Silico Drug Trial Reveals the Minimum Set of Ion Channels for Torsades de Pointes Risk Assessment. Front Pharmacol 2020; 10:1643. [PMID: 32082155 PMCID: PMC7003137 DOI: 10.3389/fphar.2019.01643] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 12/16/2019] [Indexed: 12/11/2022] Open
Abstract
Torsades de Pointes (TdP) is a type of ventricular arrhythmia which could be observed as an unwanted drug-induced cardiac side effect, and it is associated with repolarization abnormalities in single cells. The pharmacological evaluations of TdP risk in previous years mainly focused on the hERG channel due to its vital role in the repolarization of cardiomyocytes. However, only considering drug effects on hERG led to false positive predictions since the drug action on other ion channels can also have crucial regulatory effects on repolarization. To address the limitation of only evaluating hERG, the Comprehensive in Vitro Proarrhythmia Assay initiative has proposed to systematically integrate drug effects on multiple ion channels into in silico drug trial to improve TdP risk assessment. It is not clear how many ion channels are sufficient for reliable TdP risk predictions, and whether differences in IC50 and Hill coefficient values from independent sources can lead to divergent in silico prediction outcomes. The rationale of this work is to investigate the above two questions using a computationally efficient population of human ventricular cells optimized to favor repolarization abnormality. Our blinded results based on two independent data sources confirm that simulations with the optimized population of human ventricular cell models enable efficient in silico drug screening, and also provide direct observation and mechanistic analysis of repolarization abnormality. Our results show that 1) the minimum set of ion channels required for reliable TdP risk predictions are Nav1.5 (peak), Cav1.2, and hERG; 2) for drugs with multiple ion channel blockage effects, moderate IC50 variations combined with variable Hill coefficients can affect the accuracy of in silico predictions.
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Affiliation(s)
- Xin Zhou
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom
| | - Yusheng Qu
- SPARC, Amgen Research, Amgen Inc., Thousand Oaks, CA, United States
| | - Elisa Passini
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom
| | - Alfonso Bueno-Orovio
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom
| | - Yang Liu
- GAU, Amgen Research, Amgen Inc., South San Francisco, CA, United States
| | - Hugo M Vargas
- SPARC, Amgen Research, Amgen Inc., Thousand Oaks, CA, United States
| | - Blanca Rodriguez
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom
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24
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Li KHC, Lee S, Yin C, Liu T, Ngarmukos T, Conte G, Yan GX, Sy RW, Letsas KP, Tse G. Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies. IJC HEART & VASCULATURE 2020; 26:100468. [PMID: 31993492 PMCID: PMC6974766 DOI: 10.1016/j.ijcha.2020.100468] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 01/01/2020] [Accepted: 01/02/2020] [Indexed: 12/17/2022]
Abstract
Brugada syndrome (BrS) is an inherited ion channel channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Originally believed to be predominantly associated with mutations in SCN5A encoding for the cardiac sodium channel, mutations of 18 genes other than SCN5A have been implicated in the pathogenesis of BrS to date. Diagnosis is based on the presence of a spontaneous or drug-induced coved-type ST segment elevation. The predominant electrophysiological mechanism underlying BrS remains disputed, commonly revolving around the three main hypotheses based on abnormal repolarization, depolarization or current-load match. Evidence from computational modelling, pre-clinical and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening ventricular arrhythmic events. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers. Current treatment options include pharmacological therapy to reduce the occurrence of arrhythmic events or to abort these episodes, and interventions such as implantable cardioverter-defibrillator insertion or radiofrequency ablation of abnormal arrhythmic substrate.
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Affiliation(s)
- Ka Hou Christien Li
- Faculty of Medicine, Newcastle University, Newcastle, United Kingdom.,Laboratory of Cardiovascular Physiology, Li Ka Shing Institute of Health Sciences, Hong Kong, SAR, PR China
| | - Sharen Lee
- Laboratory of Cardiovascular Physiology, Li Ka Shing Institute of Health Sciences, Hong Kong, SAR, PR China
| | - Chengye Yin
- School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, PR China
| | - Tachapong Ngarmukos
- Department of Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University, Bangkok, Thailand
| | - Giulio Conte
- Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland
| | - Gan-Xin Yan
- Lankenau Institute for Medical Research and Lankenau Medical Center, Wynnewood, PA, USA
| | - Raymond W Sy
- Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.,Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
| | - Konstantinos P Letsas
- Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Athens, Greece
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, PR China.,Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China
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25
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Kurata Y, Tsumoto K, Hayashi K, Hisatome I, Kuda Y, Tanida M. Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model: Involvement of Spontaneous SR Ca 2+ Release. Front Physiol 2020; 10:1545. [PMID: 31998140 PMCID: PMC6965073 DOI: 10.3389/fphys.2019.01545] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 12/05/2019] [Indexed: 12/19/2022] Open
Abstract
Early afterdepolarization (EAD) is known to cause lethal ventricular arrhythmias in long QT syndrome (LQTS). In this study, dynamical mechanisms of EAD formation in human ventricular myocytes (HVMs) were investigated using the mathematical model developed by ten Tusscher and Panfilov (Am J Physiol Heart Circ Physiol 291, 2006). We explored how the rapid (IKr) and slow (IKs) components of delayed-rectifier K+ channel currents, L-type Ca2+ channel current (ICa L), Na+/Ca2+ exchanger current (INCX), and intracellular Ca2+ handling via the sarcoplasmic reticulum (SR) contribute to initiation, termination and modulation of phase-2 EADs during pacing in relation to bifurcation phenomena in non-paced model cells. Parameter-dependent dynamical behaviors of the non-paced model cell were determined by calculating stabilities of equilibrium points (EPs) and limit cycles, and bifurcation points to construct bifurcation diagrams. Action potentials (APs) and EADs during pacing were reproduced by numerical simulations for constructing phase diagrams of the paced model cell dynamics. Results are summarized as follows: (1) A modified version of the ten Tusscher-Panfilov model with accelerated ICaL inactivation could reproduce bradycardia-related EADs in LQTS type 2 and β-adrenergic stimulation-induced EADs in LQTS type 1. (2) Two types of EADs with different initiation mechanisms, ICaL reactivation-dependent and spontaneous SR Ca2+ release-mediated EADs, were detected. (3) Termination of EADs (AP repolarization) during pacing depended on the slow activation of IKs. (4) Spontaneous SR Ca2+ releases occurred at higher Ca2+ uptake rates, attributable to the instability of steady-state intracellular Ca2+ concentrations. Dynamical mechanisms of EAD formation and termination in the paced model cell are closely related to stability changes (bifurcations) in dynamical behaviors of the non-paced model cell, but they are model-dependent. Nevertheless, the modified ten Tusscher-Panfilov model would be useful for systematically investigating possible dynamical mechanisms of EAD-related arrhythmias in LQTS.
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Affiliation(s)
- Yasutaka Kurata
- Department of Physiology II, Kanazawa Medical University, Uchinada, Japan
| | - Kunichika Tsumoto
- Department of Physiology II, Kanazawa Medical University, Uchinada, Japan
| | - Kenshi Hayashi
- Department of Cardiovascular and Internal Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Ichiro Hisatome
- Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University, Yonago, Japan
| | - Yuhichi Kuda
- Department of Physiology II, Kanazawa Medical University, Uchinada, Japan
| | - Mamoru Tanida
- Department of Physiology II, Kanazawa Medical University, Uchinada, Japan
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26
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Kazemi B, Hajizadeh R, Ranjbar A, Sohrabi B, Vaezi H. Evaluation of T peak to end/QT and T peak to end/QTc ratios in patients with STEMI undergoing percutaneous intervention vs. thrombolytic therapy. J Electrocardiol 2020; 58:160-164. [PMID: 31895992 DOI: 10.1016/j.jelectrocard.2019.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 11/15/2019] [Accepted: 12/03/2019] [Indexed: 11/18/2022]
Abstract
INTRODUCTION The patients with ST-segment Elevation Myocardial Infarction (STEMI) are significantly at increased risk of arrhythmia. Repolarization of myocardium has been evaluated by a series of electrical parameters including T wave peak to T wave end (Tp-Te) and Tp-Te/QT ratio. Which were compared with survival outcomes between two groups of STEMI patients treated with Primary Percutaneous Coronary Intervention (PPCI) and recombinant Tissue Plasminogen Activator (r-TPA). METHODS In this prospective study, 188 patients with STEMI were included in the study. 12‑Lead ECGs were obtained from all patients on time of admission and after 24 h after treatment. After dividing the patients into two groups based on their type of treatment (PPCI or r-TPA), The Tp-Te/QT and Tp-Te/QTc ratios were calculated using ECG records. The survival outcomes were compared between two groups. RESULTS 95 patients (50.5%) underwent PPCI and 93 patients (49.5%) received r-TPA. Tp-Te/QT and Tp-Te/QTc ratios after administration of the treatments were significantly decreased in both groups (P-value = .001) with lower Tp-Te/QT and Tp-Te/QTc ratios in PPCI group (P-value = .001). 7 patients in PPCI group (7.3%) and 16 patients in r-TPA group (17.2%) were died during their hospitalization period (P-value = .04). The best combination of sensitivity and specificity of post treatment Tp-Te/QT ratio was at cutoff points of 29.4 with 82% sensitivity and 83% specificity. CONCLUSION Our study demonstrated that Tp-Te/QT and Tp-Te/QTc ratios decrease significantly after both PPCI and r-TPA therapies, but with PPCI these indexes decrease more than r-TPA, resulting a better survival outcome in patients with STEMI.
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Affiliation(s)
- Babak Kazemi
- Department of Cardiology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Reza Hajizadeh
- Department of Cardiology, Faculty of Medicine, Urmia University of Medical Science, Urmia, Iran
| | - Abdolmohammad Ranjbar
- Department of Cardiology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
| | - Bahram Sohrabi
- Department of Cardiology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Hasanali Vaezi
- Department of Cardiology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
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27
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Piccirillo G, Moscucci F, Pofi R, D'Alessandro G, Minnetti M, Isidori AM, Francomano D, Lenzi A, Puddu PE, Alexandre J, Magrì D, Aversa A. Changes in left ventricular repolarization after short-term testosterone replacement therapy in hypogonadal males. J Endocrinol Invest 2019; 42:1051-1065. [PMID: 30838540 PMCID: PMC6692303 DOI: 10.1007/s40618-019-01026-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 02/14/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Evidences suggest that androgen deficiency is associated with sudden cardiac death (SCD). Our purpose was to analyse some electrocardiographic (ECG) markers of repolarization phase in hypogonadal patients either at baseline or after testosterone replacement therapy (TRT). PATIENTS AND METHODS Baseline and after 6 months of testosterone replacement therapy, 14 hypogonadal patients and 10 age-matched controls underwent a short-term ECG recordings at rest and immediately after a maximal exercise test. The following ECG parameters have been collected: QTe (the interval between the q wave the end of T wave), QTp (the interval between the q wave and the peak of T wave), and Te (the interval between the peak and the end of T wave). RESULTS At baseline, in the hypogonadal patients, corrected QTe and QTp values were longer at rest than in the controls at rest (p < 0.05), whereas, during the recovery phase, only the QTp remained significantly longer (p < 0.05). After TRT, hypogonadal patients showed an improvement only in Te (p < 0.05). Conversely, any difference between hypogonadal patients and control subjects was found with respect to the markers of temporal dispersion of repolarization phases, except for a worse QTp → Te coherence (p = 0.001) obtained during the recovery phase. CONCLUSIONS In conclusion, at rest, hypogonadal patients suffer from a stable increase in the myocardial repolarization phase without an increase in its temporal dispersion and, hence, the SCD risk seems to be low.
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Affiliation(s)
- G Piccirillo
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, Policlinico Umberto I, "La Sapienza" University of Rome, Viale del Policlinico, 00185, Rome, Italy
| | - F Moscucci
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, Policlinico Umberto I, "La Sapienza" University of Rome, Viale del Policlinico, 00185, Rome, Italy.
| | - R Pofi
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - G D'Alessandro
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, Policlinico Umberto I, "La Sapienza" University of Rome, Viale del Policlinico, 00185, Rome, Italy
| | - M Minnetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - A M Isidori
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - D Francomano
- Division of Internal Medicine and Endocrinology, Madonna delle Grazie Hospital, Velletri, Rome, Italy
| | - A Lenzi
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - P E Puddu
- Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, Policlinico Umberto I, "La Sapienza" University of Rome, Viale del Policlinico, 00185, Rome, Italy
- EA 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie reperfusion myocardique, Université de Caen, Normandie, France
| | - J Alexandre
- EA 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie reperfusion myocardique, Université de Caen, Normandie, France
- Department of Pharmacology, CHU Caen, Caen, France
| | - D Magrì
- Dipartimento di Medicina Clinica e Molecolare, S. Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
| | - A Aversa
- Department of Experimental and Clinical Medicine, University of Catanzaro « Magna Grecia », Catanzaro, Italy
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28
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Abstract
Objective: To evaluate ventricular repolarization parameters using the interval from the peak to the end of the T wave (Tp–Te), together with QT and corrected QT (QTc) intervals, QT dispersion (QTd), and Tp-Te/QTc ratio in patients with Turner syndrome (pwTS) and to compare the results with those from healthy controls. Methods: In total, 38 patients previously diagnosed with Turner syndrome (TS) and 35 healthy girls (controls) were included in our cross-sectional study. Twelve-lead electrocardiography (ECG) and echocardiography after a 30-min rest were performed. The QT, QTc, QTd, Tp-Te interval, and Tp-Te/QTc ratio were determined. Results: No differences in age or sex were observed between the groups. QT intervals were similar in both groups [pwTS: 354.76±25.33 ms, controls (C): 353.29±17.51 ms, p=0.775]. pwTS had significantly longer QTc and QTd than controls (411.87±22.66 ms vs. 392.06±13.21 ms, p<0.001 and 40.31±2.02 ms vs. 37.54±1.83 ms, p<0.001, respectively). Similarly, the Tp-Te interval and Tp-Te/QTc ratio were significantly longer in pwTS than in controls (71.89±3.39 ms vs. 65.34±2.88 ms, p<0.001 and 0.17±0.01 vs. 0.16±0.01, p=0.01). Conclusion: As pwTS have longer QTc, QTd, Tp–Te interval, and Tp-Te/QTc ratio, an annual follow-up with ECG can provide awareness and even prevent sudden death in them. Also avoiding the use of drugs that makes repolarization anomaly and having knowledge about the side effects of these drugs are essential in pwTS.
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29
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Lopez-Perez A, Sebastian R, Izquierdo M, Ruiz R, Bishop M, Ferrero JM. Personalized Cardiac Computational Models: From Clinical Data to Simulation of Infarct-Related Ventricular Tachycardia. Front Physiol 2019; 10:580. [PMID: 31156460 PMCID: PMC6531915 DOI: 10.3389/fphys.2019.00580] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 04/25/2019] [Indexed: 12/20/2022] Open
Abstract
In the chronic stage of myocardial infarction, a significant number of patients develop life-threatening ventricular tachycardias (VT) due to the arrhythmogenic nature of the remodeled myocardium. Radiofrequency ablation (RFA) is a common procedure to isolate reentry pathways across the infarct scar that are responsible for VT. Unfortunately, this strategy show relatively low success rates; up to 50% of patients experience recurrent VT after the procedure. In the last decade, intensive research in the field of computational cardiac electrophysiology (EP) has demonstrated the ability of three-dimensional (3D) cardiac computational models to perform in-silico EP studies. However, the personalization and modeling of certain key components remain challenging, particularly in the case of the infarct border zone (BZ). In this study, we used a clinical dataset from a patient with a history of infarct-related VT to build an image-based 3D ventricular model aimed at computational simulation of cardiac EP, including detailed patient-specific cardiac anatomy and infarct scar geometry. We modeled the BZ in eight different ways by combining the presence or absence of electrical remodeling with four different levels of image-based patchy fibrosis (0, 10, 20, and 30%). A 3D torso model was also constructed to compute the ECG. Patient-specific sinus activation patterns were simulated and validated against the patient's ECG. Subsequently, the pacing protocol used to induce reentrant VTs in the EP laboratory was reproduced in-silico. The clinical VT was induced with different versions of the model and from different pacing points, thus identifying the slow conducting channel responsible for such VT. Finally, the real patient's ECG recorded during VT episodes was used to validate our simulation results and to assess different strategies to model the BZ. Our study showed that reduced conduction velocities and heterogeneity in action potential duration in the BZ are the main factors in promoting reentrant activity. Either electrical remodeling or fibrosis in a degree of at least 30% in the BZ were required to initiate VT. Moreover, this proof-of-concept study confirms the feasibility of developing 3D computational models for cardiac EP able to reproduce cardiac activation in sinus rhythm and during VT, using exclusively non-invasive clinical data.
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Affiliation(s)
- Alejandro Lopez-Perez
- Center for Research and Innovation in Bioengineering (Ci2B), Universitat Politècnica de València, Valencia, Spain
| | - Rafael Sebastian
- Computational Multiscale Simulation Lab (CoMMLab), Universitat de València, Valencia, Spain
| | - M Izquierdo
- INCLIVA Health Research Institute, Valencia, Spain.,Arrhythmia Unit, Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Ricardo Ruiz
- INCLIVA Health Research Institute, Valencia, Spain.,Arrhythmia Unit, Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Martin Bishop
- Division of Imaging Sciences & Biomedical Engineering, Department of Biomedical Engineering, King's College London, London, United Kingdom
| | - Jose M Ferrero
- Center for Research and Innovation in Bioengineering (Ci2B), Universitat Politècnica de València, Valencia, Spain
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30
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Uchida S, Asai Y, Kariya Y, Tsumoto K, Hibino H, Honma M, Abe T, Nin F, Kurata Y, Furutani K, Suzuki H, Kitano H, Inoue R, Kurachi Y. Integrative and theoretical research on the architecture of a biological system and its disorder. J Physiol Sci 2019; 69:433-451. [PMID: 30868372 PMCID: PMC6456489 DOI: 10.1007/s12576-019-00667-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 02/08/2019] [Indexed: 11/28/2022]
Abstract
An organism stems from assemblies of a variety of cells and proteins. This complex system serves as a unit, and it exhibits highly sophisticated functions in response to exogenous stimuli that change over time. The complete sequencing of the entire human genome has allowed researchers to address the enigmas of life and disease at the gene- or molecular-based level. The consequence of such studies is the rapid accumulation of a multitude of data at multiple levels, ranging from molecules to the whole body, that has necessitated the development of entirely new concepts, tools, and methodologies to analyze and integrate these data. This necessity has given birth to systems biology, an advanced theoretical and practical research framework that has totally changed the directions of not only basic life science but also medicine. During the symposium of the 95th Annual Meeting of The Physiological Society of Japan 2018, five researchers reported on their respective studies on systems biology. The topics included reactions of drugs, ion-transport architecture in an epithelial system, multi-omics in renal disease, cardiac electrophysiological systems, and a software platform for computer simulation. In this review article these authors have summarized recent achievements in the field and discuss next-generation studies on health and disease.
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Affiliation(s)
- Shinichi Uchida
- Department of Nephrology, Graduate Schools of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan
| | - Yoshiyuki Asai
- Department of Systems Bioinformatics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Yoshiaki Kariya
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kunichika Tsumoto
- Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Suita, Japan
- Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Japan
- Department of Physiology II, Kanazawa Medical University, Ishikawa, 920-0293, Japan
| | - Hiroshi Hibino
- Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
- AMED-CREST, AMED, Niigata, Japan.
| | - Masashi Honma
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeshi Abe
- Department of Systems Bioinformatics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan
| | - Fumiaki Nin
- Department of Molecular Physiology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan
- AMED-CREST, AMED, Niigata, Japan
| | - Yasutaka Kurata
- Department of Physiology II, Kanazawa Medical University, Ishikawa, 920-0293, Japan
| | - Kazuharu Furutani
- Department of Physiology and Membrane Biology, University of California Davis, Davis, 95616, USA
| | - Hiroshi Suzuki
- Department of Pharmacy, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroaki Kitano
- The Systems Biology Institute, Shinagawa-ku, Tokyo, 108-0071, Japan
| | - Ryuji Inoue
- Department of Physiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
| | - Yoshihisa Kurachi
- Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Osaka University, Suita, Japan.
- Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Japan.
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Reynard JT, Oshodi OM, Lai JC, Lai RW, Bazoukis G, Fragakis N, Letsas KP, Korantzopoulos P, Liu FZ, Liu T, Xia Y, Tse G, Li CK. Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform. Minerva Cardioangiol 2019; 67:131-144. [PMID: 30260143 DOI: 10.23736/s0026-4725.18.04775-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.
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Affiliation(s)
- Jack T Reynard
- Faculty of Medicine, Newcastle University, Newcastle Upon Tyne, UK
| | | | - Jenny C Lai
- Faculty of Medicine, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Rachel W Lai
- Faculty of Medicine, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - George Bazoukis
- Laboratory of Cardiac Electrophysiology, Second Department of Cardiology, Evangelismos General Hospital of Athens, Athens, Greece
| | - Nikolaos Fragakis
- Third Department of Cardiology, Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- First Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece
| | - Konstantinos P Letsas
- Laboratory of Cardiac Electrophysiology, Second Department of Cardiology, Evangelismos General Hospital of Athens, Athens, Greece
| | - Panagiotis Korantzopoulos
- Third Department of Cardiology, Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- First Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece
| | - Fang-Zhou Liu
- Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital affiliated to South China University of Technology, Guangzhou, China
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yunlong Xia
- Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Gary Tse
- Faculty of Medicine, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Christien K Li
- Faculty of Medicine, Newcastle University, Newcastle Upon Tyne, UK -
- Faculty of Medicine, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
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BURAK C, BAYSAL E, SÜLEYMANOĞLU M, YAYLA Ç, CAY S, KERVAN Ü. Evaluation of myocardial dispersion of repolarization in patients with heart transplantation. Turk J Med Sci 2019; 49:212-216. [PMID: 30761885 PMCID: PMC7350875 DOI: 10.3906/sag-1807-90] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Background/aim The number of patients with heart transplantation has dramatically increased in the last decade. Considerable studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. We analyzed the dispersion of myocardial repolarization using electrocardiographic Tp-e interval and Tp-e/QTc ratio in patients with heart transplantation. Materials and methods This observational study included 38 patients (12 female and 26 male) with heart transplantation and 38 well-matched controls. From electrocardiograms, Tp-e interval and Tp-e/QTc ratio were calculated and compared between the 2 groups. Results Noninvasive arrhythmia indicators including Tp-e interval (84.63 ± 14.17 ms vs 71.82 ± 7.47 ms, P < 0.001), Tp-e/QTc ratio (0.19 ± 0.04 vs 0.16 ± 0.02, P < 0.001) and QTc interval except QT interval were significantly higher in transplanted hearts compared to normal hearts. Conclusion Patients with heart transplantation have increased myocardial dispersion of repolarization.
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Affiliation(s)
- Cengiz BURAK
- Department of Cardiology, Mardin State Hospital, MardinTurkey
- * To whom correspondence should be addressed. E-mail:
| | - Erkan BAYSAL
- Department of Cardiology, Diyarbakır Gazi Yaşargil Training and Research Hospital, DiyarbakırTurkey
| | | | - Çağrı YAYLA
- Department of Cardiology and Cardiovascular Surgery, Türkiye Yüksek İhtisas Training and Research Hospital, AnkaraTurkey
| | - Serkan CAY
- Department of Cardiology and Cardiovascular Surgery, Türkiye Yüksek İhtisas Training and Research Hospital, AnkaraTurkey
| | - Ümit KERVAN
- Department of Cardiology and Cardiovascular Surgery, Türkiye Yüksek İhtisas Training and Research Hospital, AnkaraTurkey
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Öztürk M, Turan OE, Karaman K, Bilge N, Ceyhun G, Aksu U, Aksakal E, Gulcu O, Kalkan K, Demirelli S. Evaluation of ventricular repolarization parameters during migraine attacks. J Electrocardiol 2018; 53:66-70. [PMID: 30684863 DOI: 10.1016/j.jelectrocard.2018.12.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/10/2018] [Accepted: 12/21/2018] [Indexed: 01/03/2023]
Abstract
AIMS Migraine is a chronic neurovascular disorder characterized by intermittent episodes of severe headache. Abnormalities in the autonomic nervous system (sympathetic and parasympathetic nervous systems) have been detected during migraine-free periods in patients with migraine. In these patients, disrupted autonomic innervations of the heart and coronary arteries may lead to electrocardiographic changes during a migraine attack. T-wave peak-to-end interval (Tp-e interval) and Tp-e/QT ratio are relatively new markers of ventricular arrhythmogenesis and repolarization heterogeneity. In the present observational study, we investigated the changes in ventricular repolarization during migraine attacks and attack-free periods by performing 12‑lead electrocardiography (ECG). METHODS This study included 63 patients (54 [86%] women; mean age: 33.3 ± 9.9 years) with migraine. The QT and corrected QT (QTc) intervals, Tp-e interval, and Tp-e/QT ratio of the patients during migraine attacks and attack-free periods were measured by performing 12‑lead ECG. RESULTS The QT and QTc intervals, Tp-e interval, and Tp-e/QT ratio were higher during migraine attacks than during attack-free periods (P < 0.001 for all). CONCLUSION These results indicate that migraine attacks are associated with an increase in ventricular repolarization parameters compared with attack-free periods possibly because of the dysregulation of the autonomic nervous system.
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Affiliation(s)
- Mustafa Öztürk
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey.
| | | | - Kayıhan Karaman
- Department of Cardiology, Gaziosmanpaşa University, Faculty of Medicine, Tokat, Turkey
| | - Nuray Bilge
- Department of Neurology, Atatürk University, Faculty of Medicine, Erzurum, Turkey
| | - Gökhan Ceyhun
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Ugur Aksu
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Emrah Aksakal
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Oktay Gulcu
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Kamuran Kalkan
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Selami Demirelli
- Department of Cardiology, University of Health Sciences, Erzurum Education and Research Hospital, Erzurum, Turkey
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Santiago A, Aguado-Sierra J, Zavala-Aké M, Doste-Beltran R, Gómez S, Arís R, Cajas JC, Casoni E, Vázquez M. Fully coupled fluid-electro-mechanical model of the human heart for supercomputers. INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING 2018; 34:e3140. [PMID: 30117302 DOI: 10.1002/cnm.3140] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 04/28/2018] [Accepted: 07/22/2018] [Indexed: 05/12/2023]
Abstract
In this work, we present a fully coupled fluid-electro-mechanical model of a 50th percentile human heart. The model is implemented on Alya, the BSC multi-physics parallel code, capable of running efficiently in supercomputers. Blood in the cardiac cavities is modeled by the incompressible Navier-Stokes equations and an arbitrary Lagrangian-Eulerian (ALE) scheme. Electrophysiology is modeled with a monodomain scheme and the O'Hara-Rudy cell model. Solid mechanics is modeled with a total Lagrangian formulation for discrete strains using the Holzapfel-Ogden cardiac tissue material model. The three problems are simultaneously and bidirectionally coupled through an electromechanical feedback and a fluid-structure interaction scheme. In this paper, we present the scheme in detail and propose it as a computational cardiac workbench.
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Affiliation(s)
- Alfonso Santiago
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Jazmín Aguado-Sierra
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Miguel Zavala-Aké
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | | | - Samuel Gómez
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Ruth Arís
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Juan C Cajas
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Eva Casoni
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
| | - Mariano Vázquez
- Department of Computer Applications in Science and Engineering, Barcelona Supercomputing Center (BSC), Barcelona, Spain
- Instituto de Investigación en Inteligencia Artificial (IIIA), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain
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Piccirillo G, Moscucci F, Mastropietri F, Di Iorio C, Mariani MV, Fabietti M, Stricchiola GM, Parrotta I, Sardella G, Mancone M, Magrì D. Possible predictive role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients: preliminary data. Clin Interv Aging 2018; 13:1657-1667. [PMID: 30237702 PMCID: PMC6138964 DOI: 10.2147/cia.s170226] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Objectives To evaluate the predicative power of the electrical risk score (ERS), a noninvasive and inexpensive test obtained by means of a standard 12-lead electrocardiogram (ECG), in a cohort of elderly patients who had undergone transcatheter aortic valve replacement (TAVR). Methods Survivors and non-survivors after TAVR at 1-year follow-up were compared in respect to the pre-procedural ERS as well as a number of other clinical and instrumental variables. ERS is composed of seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms); left ventricular hypertrophy (Sokolow–Lyon criteria); delayed QRS transition zone (≥ V4); frontal QRS-T angle (>90°); long QTBazett (>450 ms for men and >460 in women) or JTBazett (330 ms for men and >340 ms for women); and long Tpeak to Tend interval (Tp-e) (>89 ms). The trial was registered in ClinicalTrials.gov as NCT03145376. Results A total of 40 patients were evaluated. During the follow-up, the all-cause mortality rate was 25% (ten patients) with 15% of cardiovascular death (six patients). The ERS was the strongest predictor of all-cause (odds ratio 3.73, 95% CI: 1.44–9.66, P<0.05) or cardiovascular (odds ratio 3.95, 95% CI: 1.09–14.27, P<0.05) mortality. Receiver operating characteristic curves showed that ERS had the widest significant sensitivity-specificity area under the curve (AUC) predicting all-cause (AUC: 0.855, P<0.05) or cardiovascular mortality (AUC: 0.908, P<0.05). Conclusion ERS seems to be a useful noninvasive tool able to stratify the risk of mortality in 1-year follow-up of TAVR patients. These findings, however, require larger trials to be confirmed.
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Affiliation(s)
- Gianfranco Piccirillo
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Federica Moscucci
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Fabiola Mastropietri
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Claudia Di Iorio
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Marco Valerio Mariani
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Marcella Fabietti
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Gaetana M Stricchiola
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Ilaria Parrotta
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Gennaro Sardella
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Massimo Mancone
- Department of Cardiovascular, Respiratory, Nephrological, Anesthesiologic, and Geriatric Sciences, Policlinico Umberto I, "La Sapienza" University of Rome, Rome, Italy,
| | - Damiano Magrì
- Department of Molecular and Clinical Medicine, S. Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
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Sicouri S, Antzelevitch C. Mechanisms Underlying the Actions of Antidepressant and Antipsychotic Drugs That Cause Sudden Cardiac Arrest. Arrhythm Electrophysiol Rev 2018; 7:199-209. [PMID: 30416734 PMCID: PMC6141916 DOI: 10.15420/aer.2018.29.2] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 06/19/2018] [Indexed: 12/18/2022] Open
Abstract
A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. While many antidepressants and antipsychotics have been linked to QT prolongation and the development of torsade de pointes arrhythmias, some have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This article examines the arrhythmic liability of antipsychotic and antidepressant drugs capable of inducing long QT and/or Brugada syndrome phenotypes. The goal of this article is to provide an update on the ionic and cellular mechanisms thought to be involved in, and the genetic and environmental factors that predispose to, the development of cardiac arrhythmias and sudden cardiac death among patients taking antidepressant and antipsychotic drugs that are in clinical use.
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Affiliation(s)
- Serge Sicouri
- Lankenau Institute for Medical ResearchWynnewood, PA, USA
| | - Charles Antzelevitch
- Lankenau Institute for Medical ResearchWynnewood, PA, USA
- Lankenau Heart InstituteWynnewood, PA
- Sidney Kimmel Medical College of Thomas Jefferson UniversityPhiladelphia, PA, USA
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Tomoum H, Habeeb N, Elagouza I, Mobarez H. Paediatric breath-holding spells are associated with autonomic dysfunction and iron deficiency may play a role. Acta Paediatr 2018; 107:653-657. [PMID: 29210110 DOI: 10.1111/apa.14177] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 11/11/2017] [Accepted: 12/01/2017] [Indexed: 11/30/2022]
Abstract
AIM This study assessed cardiac performance and iron in subjects aged 12-36 months with breath-holding spells (BHSs). METHODS We consecutively recruited 40 subjects (55% male) experiencing BHSs from the general paediatric outpatients department at the Children's Hospital, Ain Shams University, Egypt, from 2015 to 2016. The 20 matched comparisons were mainly healthy siblings. The workup included iron levels and electrocardiograms. RESULTS The age at the onset of BHSs was 5-24 months with a median monthly frequency of 13. Almost two-thirds of the patients had cyanotic spells, and one-third had pallid spells, lasting 25-90 seconds. Lower serum iron levels and higher QT dispersion and T-wave dispersion were recorded in patients than the comparison group, and 4.8% had dysrhythmia and bradycardia. We observed higher durations of bradycardia during attacks and higher occurrences of dysrhythmia during cyanotic spells, which were more frequent in patients with prolonged or frequent BHSs. CONCLUSION Our study of patients aged 12-13 months supported the theory of autonomic dysfunction in BHSs. The ECG findings, especially in patients with prolonged or frequent spells, need to be studied further to evaluate the risk of life-threatening events. Iron deficiency may play a role in autonomic dysfunction in patients with BHSs.
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Affiliation(s)
- H Tomoum
- Department of Paediatrics; Faculty of Medicine; Ain Shams University; Cairo Egypt
| | - N Habeeb
- Department of Paediatrics; Faculty of Medicine; Ain Shams University; Cairo Egypt
| | - I Elagouza
- Department of Paediatrics; Faculty of Medicine; Ain Shams University; Cairo Egypt
| | - H Mobarez
- Department of Paediatrics; Faculty of Medicine; Ain Shams University; Cairo Egypt
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Meta-analysis of T-wave indices for risk stratification in myocardial infarction. JOURNAL OF GERIATRIC CARDIOLOGY : JGC 2018; 14:776-779. [PMID: 29581718 PMCID: PMC5863057 DOI: 10.11909/j.issn.1671-5411.2017.12.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Antzelevitch C, Di Diego JM, Argenziano M. Tpeak-Tend as a predictor of ventricular arrhythmogenesis. Int J Cardiol 2018; 249:75-76. [PMID: 29121761 DOI: 10.1016/j.ijcard.2017.09.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 09/06/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Charles Antzelevitch
- Lankenau Institute for Medical Research, Wynnewood, PA, United States; Lankenau Heart Institute, Main Line Health System, Wynnewood, PA, United States; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States.
| | - José M Di Diego
- Lankenau Institute for Medical Research, Wynnewood, PA, United States
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40
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Meta-analysis of T peak-T end and T peak-T end/QT ratio for risk stratification in congenital long QT syndrome. J Electrocardiol 2018; 51:396-401. [PMID: 29550106 DOI: 10.1016/j.jelectrocard.2018.03.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Revised: 02/13/2018] [Accepted: 03/06/2018] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND OBJECTIVES Congenital long QT syndrome (LQTS) predisposes affected individuals to ventricular tachycardia/fibrillation (VF/VF), potentially resulting in sudden cardiac death. The Tpeak-Tend interval and the Tpeak-Tend/QT ratio, electrocardiographic markers of dispersion of ventricular repolarization, were proposed for risk stratification but their predictive values in LQTS have been controversial. A systematic review and meta-analysis was conducted to examine the value of Tpeak-Tend intervals and Tpeak-Tend/QT ratios in predicting arrhythmic and mortality outcomes in congenital LQTS. METHOD PubMed and Embase databases were searched until 9th May 2017, identifying 199 studies. RESULTS Five studies on long QT syndrome were included in the final meta-analysis. Tpeak-Tend intervals were longer (mean difference [MD]: 13ms, standard error [SE]: 4ms, P=0.002; I2=34%) in congenital LQTS patients with adverse events [syncope, ventricular arrhythmias or sudden cardiac death] compared to LQTS patients without such events. By contrast, Tpeak-Tend/QT ratios were not significantly different between the two groups (MD: 0.02, SE: 0.02, P=0.26; I2=0%). CONCLUSION This meta-analysis showed that Tpeak-Tend interval is significant higher in individuals who are at elevated risk of adverse events in congenital LQTS, offering incremental value for risk stratification.
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Conlon R, Tanner R, David S, Szeplaki G, Galvin J, Keaney J, Keelan E, Boles U. Evaluation of the Tp-Te Interval, QTc and P-Wave Dispersion in Patients With Coronary Artery Ectasia. Cardiol Res 2018; 8:280-285. [PMID: 29317970 PMCID: PMC5755659 DOI: 10.14740/cr631w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 11/30/2017] [Indexed: 11/21/2022] Open
Abstract
Background Coronary artery ectasia (CAE) is defined as a diffuse dilatation of the diameter of the ectatic segment of the coronary artery, 1.5 times greater than that of the adjacent segment. The Tp-Te interval, P-wave and QTc dispersions are relatively new electrocardiographic markers associated with an increased risk of developing arrhythmias. Despite CAE increasing in prevalence in recent years, there is a sparsity of data available about its arrhythmogenic effect. The aim of the study was to evaluate QTc, P-wave dispersion and Tp-Te and Tp-Te/QT ratio in patients with CAE. Methods A retrospective comparative study was designed for consecutive age- and sex-matched patients. Twenty patients with isolated CAE (group 1) and 20 control subjects (group 2), with normal coronary arteries, were included. All patients presented with chest pain and coronary angiogram was indicated. Outcome measures included Tp-Te interval, Tp-Te/QT ratio, QTc dispersion and P-wave dispersion. Measurement of electrocardiogram (ECG) parameters was conducted using standardized digital online software. Descriptive and inferential statistics were performed. Results Mean Tp-Te (95.5 ± 9.01 ms) and Tp-Te/QT ratio (0.22 ± 0.02) were significantly prolonged in CAE group (Tp-Te: 84 ± 5.62 ms, P = 0.00009; Tp-Te/QT ratio: 0.20 ± 0.01, P = 0.00004). In addition, QTc (31.2 ± 3.71 ms) and P-wave dispersion (31.9 ± 5.46 ms) were significantly increased in comparison to the control group (QTc: 27.6 ± 2.82 ms, P = 0.00532 and 20 ± 3.77 ms, P = 0.00003 respectively). However, there was no difference in ventricular activation time (VAT) between groups. Conclusions CAE ECGs were found to be associated with increased Tp-Te, Tp-Te/QT ratio, QTc intervals and P-wave dispersions. This may suggest that CAE existence has a pro-arrhythmogenic nature.
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Affiliation(s)
- Ronan Conlon
- Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland
| | - Richard Tanner
- Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland
| | - Santhosh David
- Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland
| | - Gabor Szeplaki
- Heart and Vascular Center, Mater Private Hospital, Dublin 2, Ireland
| | - Joseph Galvin
- Heart and Vascular Center, Mater Private Hospital, Dublin 2, Ireland
| | - John Keaney
- Heart and Vascular Center, Mater Private Hospital, Dublin 2, Ireland
| | - Edward Keelan
- Heart and Vascular Center, Mater Private Hospital, Dublin 2, Ireland
| | - Usama Boles
- Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland.,Heart and Vascular Center, Mater Private Hospital, Dublin 2, Ireland
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Banavalikar B, Thajudeen A, Namboodiri N, Nair KKM, Pushpangadhan AS, Valaparambil AK. Long-term effects of cardiac resynchronization therapy on electrical remodeling in heart failure-A prospective study. Pacing Clin Electrophysiol 2017; 40:1279-1285. [PMID: 28901586 DOI: 10.1111/pace.13193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Revised: 08/08/2017] [Accepted: 08/28/2017] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Effects of cardiac resynchronization therapy (CRT) on arrhythmogenicity and sudden death have not been fully ascertained. CRT has been shown to increase transmural dispersion of repolarization (TDR) immediately on implantation, which may favorably remodel on long-term follow-up. However, such a hypothesis has not been prospectively evaluated. METHODS AND RESULTS We included 35 consecutive patients who underwent CRT implantation between September 2013 and August 2014 (mean age 56.8 ± 11.09 years; 71.43% males). QT and Tpeak-Tend (Tp-e) intervals were measured during endocardial (RVendoP), epicardial (LVepiP), and biventricular pacing (BiVP) at CRT implantation and 1-year follow-up. Compared to RVendoP (130.41 ± 16.75 ms), Tp-e was significantly prolonged during BiVP (142.06 ± 21.98 ms; P < 0.001) and LVepiP (183.45 ± 27.87 ms; P < 0.001) at baseline. There was a significant decrease in Tp-e during BiVP on follow-up (117.93 ± 15.03 ms; P < 0.001). High responders had significantly lower Tp-e at 1 year compared to low responders (113.16 ± 14.3 ms vs 129.59 ± 9.75 ms, P = 0.004). Tp-e at 1 year had strong negative correlation with reduction in LV end-systolic volumes (r = - 0.51; P = 0.003). Seven patients with sustained ventricular arrhythmias during follow-up had significantly longer baseline Tp-e compared to those without arrhythmias (158.19 ± 17.59 ms vs 139.72 ± 20.94 ms, P = 0.043). A baseline Tp-e value of ≥ 148 ms had a specificity of 75% and sensitivity of 71% to predict ventricular arrhythmias. CONCLUSIONS Baseline TDR is greater during BiVP and LV epiP compared with RVendoP in patients with heart failure. However, BiVP causes a significant reduction in TDR reflective of reverse electrical remodeling on long-term follow-up.
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Affiliation(s)
- Bharatraj Banavalikar
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
| | - Anees Thajudeen
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
| | - Narayanan Namboodiri
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
| | - Krishna Kumar Mohanan Nair
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
| | - Abhilash Srivilasam Pushpangadhan
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
| | - Ajit Kumar Valaparambil
- Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695011, India
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Hysteretic Dynamics of Multi-Stable Early Afterdepolarisations with Repolarisation Reserve Attenuation: A Potential Dynamical Mechanism for Cardiac Arrhythmias. Sci Rep 2017; 7:10771. [PMID: 28883639 PMCID: PMC5589958 DOI: 10.1038/s41598-017-11355-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 08/23/2017] [Indexed: 02/08/2023] Open
Abstract
Some cardiovascular and non-cardiovascular drugs frequently cause excessive prolongation of the cardiac action potential (AP) and lead to the development of early afterdepolarisations (EADs), which trigger lethal ventricular arrhythmias. Combining computer simulations in APs with numerical calculations based on dynamical system theory, we investigated stability changes of APs observed in a paced human ventricular myocyte model by decreasing and/or increasing the rapid (IKr) and slow (IKs) components of delayed rectifying K+ current. Upon reducing IKr, the APs without EADs (no-EAD response) showed gradual prolongation of AP duration (APD), and were annihilated without AP configuration changes due to the occurrence of saddle-node bifurcations. This annihilation caused a transition to an AP with EADs as a new stable steady state. Furthermore, reducing repolarisation currents (repolarisation reserve attenuation) evoked multi-stable states consisting of APs with different APDs, and caused multiple hysteretic dynamics. Depending on initial ion circumstances within ventricular myocytes, these multi-stable AP states might increase the local/global heterogeneity of AP repolarisations in the ventricle. Thus, the EAD-induced arrhythmias with repolarisation reserve attenuation might be attributed to the APD variability caused by multi-stability in cardiac AP dynamics.
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Oskouie SK, Prenner SB, Shah SJ, Sauer AJ. Differences in Repolarization Heterogeneity Among Heart Failure With Preserved Ejection Fraction Phenotypic Subgroups. Am J Cardiol 2017; 120:601-606. [PMID: 28651852 DOI: 10.1016/j.amjcard.2017.05.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 05/04/2017] [Accepted: 05/04/2017] [Indexed: 12/22/2022]
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome associated with multiple medical comorbidities and pathophysiologic pathways or phenotypes. We recently developed a phenomapping method combining deep phenotyping with machine learning analysis to classify HFpEF patients into 3 clinically distinct phenotypic subgroups (phenogroups) with different clinical outcomes. Phenogroup #1 was younger with lower B-type natriuretic peptide levels, phenogroup #2 had the highest prevalence of obesity and diabetes mellitus, and phenogroup #3 was the oldest with the most factors for chronic kidney disease, the most dysfunctional myocardial mechanics, and the highest adverse outcomes. The pathophysiological differences between these phenogroups, however, remain incompletely described. We sought to evaluate whether these 3 groups differ on the basis of repolarization heterogeneity, which has previously been linked to adverse outcomes in HFpEF. The T-peak to T-end (TpTe) interval, a well-validated index of repolarization heterogeneity, was measured by 2 readers blinded to each other and all other clinical data on the electrocardiograms of 201 HFpEF patients enrolled in a systematic observational study. TpTe duration was associated with higher B-type natriuretic peptide level (p = 0.006), increased QRS-T angle (p = 0.008), and lower septal e' velocity (p = 0.007). TpTe duration was greatest in phenogroup #3 (100.4 ± 24.5 ms) compared with phenogroups #1 (91.2 ± 17.3 ms) and #2 (90.2 ± 17.0 ms) (p = 0.0098). On multivariable analyses, increased TpTe was independently associated with the high-risk phenogroup #3 classification. In conclusion, repolarization heterogeneity is a marker of a specific subset of HFpEF patients identified using unsupervised machine learning analysis and therefore may be a key pathophysiologic marker in this subset of HFpEF patients.
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Lee HC, Rudy Y, Liang H, Chen CC, Luo CH, Sheu SH, Cui J. Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and Its Potential Therapeutic Targets: Insights from Modeling. J Med Biol Eng 2017; 37:780-789. [PMID: 29213224 PMCID: PMC5714284 DOI: 10.1007/s40846-017-0257-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gain-of-function mutations in the pore-forming subunit of IKs channels, KCNQ1, lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant IKs channels cause SQTS and the possibility of IKs-specific pharmacological treatment remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect on IKs gating properties and changes in the action potentials (AP) of human ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes with and without β-adrenergic stimulation. V141M KCNQ1 caused a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to IKs accumulation. V141M KCNQ1 also caused a leftward shift of the conductance-voltage curve compared to wild type (WT) IKs (V1/2 = 33.6 ± 4.0 mV for WT, and 24.0 ± 1.3 mV for heterozygous V141M). A Markov model of heterozygous V141M mutant IKs was developed and incorporated into the O’Hara–Rudy model. Compared to the WT, AP simulations demonstrated marked rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M AP simulations, especially under β-adrenergic stimulation. Computational simulations identified specific IK1 blockade as a beneficial pharmacologic target for reducing the transmural APD heterogeneity associated with V141M KCNQ1 mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural APD heterogeneity under β-adrenergic stimulation. Computational simulations identified IK1 blockers as a potential antiarrhythmic drug of choice for SQTS.
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Affiliation(s)
- Hsiang-Chun Lee
- Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, MO 63130, USA.,Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung 807, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.,Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.,Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.,Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan
| | - Yoram Rudy
- Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Hongwu Liang
- Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, MO 63130, USA
| | - Chih-Chieh Chen
- Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan
| | - Ching-Hsing Luo
- Department of Electric Engineering, National Cheng Kung University, Tainan 804, Taiwan
| | - Sheng-Hsiung Sheu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung 807, Taiwan.,Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.,Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Jianmin Cui
- Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, St. Louis, MO 63130, USA
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Osadchii OE. Role of abnormal repolarization in the mechanism of cardiac arrhythmia. Acta Physiol (Oxf) 2017; 220 Suppl 712:1-71. [PMID: 28707396 DOI: 10.1111/apha.12902] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In cardiac patients, life-threatening tachyarrhythmia is often precipitated by abnormal changes in ventricular repolarization and refractoriness. Repolarization abnormalities typically evolve as a consequence of impaired function of outward K+ currents in cardiac myocytes, which may be caused by genetic defects or result from various acquired pathophysiological conditions, including electrical remodelling in cardiac disease, ion channel modulation by clinically used pharmacological agents, and systemic electrolyte disorders seen in heart failure, such as hypokalaemia. Cardiac electrical instability attributed to abnormal repolarization relies on the complex interplay between a provocative arrhythmic trigger and vulnerable arrhythmic substrate, with a central role played by the excessive prolongation of ventricular action potential duration, impaired intracellular Ca2+ handling, and slowed impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account for the dependence of arrhythmic vulnerability on the location of the ventricular pacing site. Finally, the review clarifies the electrophysiological basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the clinical importance and pathophysiology of drug-induced arrhythmia, with particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na+ channel blockers, and class III antiarrhythmic agents that block the delayed rectifier K+ channel (dofetilide).
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Affiliation(s)
- O. E. Osadchii
- Department of Health Science and Technology; University of Aalborg; Aalborg Denmark
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48
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Lee MY. T wave. INTERNATIONAL JOURNAL OF ARRHYTHMIA 2017. [DOI: 10.18501/arrhythmia.2017.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Hegyi B, Horváth B, Váczi K, Gönczi M, Kistamás K, Ruzsnavszky F, Veress R, Izu LT, Chen-Izu Y, Bányász T, Magyar J, Csernoch L, Nánási PP, Szentandrássy N. Ca 2+-activated Cl - current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization. J Mol Cell Cardiol 2017; 109:27-37. [PMID: 28668303 DOI: 10.1016/j.yjmcc.2017.06.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 06/26/2017] [Accepted: 06/28/2017] [Indexed: 01/26/2023]
Abstract
The role of Ca2+-activated Cl- current (ICl(Ca)) in cardiac arrhythmias is still controversial. It can generate delayed afterdepolarizations in Ca2+-overloaded cells while in other studies incidence of early afterdepolarization (EAD) was reduced by ICl(Ca). Therefore our goal was to examine the role of ICl(Ca) in spatial and temporal heterogeneity of cardiac repolarization and EAD formation. Experiments were performed on isolated canine cardiomyocytes originating from various regions of the left ventricle; subepicardial, midmyocardial and subendocardial cells, as well as apical and basal cells of the midmyocardium. ICl(Ca) was blocked by 0.5mmol/L 9-anthracene carboxylic acid (9-AC). Action potential (AP) changes were tested with sharp microelectrode recording. Whole-cell 9-AC-sensitive current was measured with either square pulse voltage-clamp or AP voltage-clamp (APVC). Protein expression of TMEM16A and Bestrophin-3, ion channel proteins mediating ICl(Ca), was detected by Western blot. 9-AC reduced phase-1 repolarization in every tested cell. 9-AC also increased AP duration in a reverse rate-dependent manner in all cell types except for subepicardial cells. Neither ICl(Ca) density recorded with square pulses nor the normalized expressions of TMEM16A and Bestrophin-3 proteins differed significantly among the examined groups of cells. The early outward component of ICl(Ca) was significantly larger in subepicardial than in subendocardial cells in APVC setting. Applying a typical subepicardial AP as a command pulse resulted in a significantly larger early outward component in both subepicardial and subendocardial cells, compared to experiments when a typical subendocardial AP was applied. Inhibiting ICl(Ca) by 9-AC generated EADs at low stimulation rates and their incidence increased upon beta-adrenergic stimulation. 9-AC increased the short-term variability of repolarization also. We suggest a protective role for ICl(Ca) against risk of arrhythmias by reducing spatial and temporal heterogeneity of cardiac repolarization and EAD formation.
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Affiliation(s)
- Bence Hegyi
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Department of Pharmacology, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 3503, Davis, CA 95616, USA
| | - Balázs Horváth
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Faculty of Pharmacy, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Krisztina Váczi
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Mónika Gönczi
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; MTA-DE Momentum, Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Kornél Kistamás
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Ferenc Ruzsnavszky
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Roland Veress
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Leighton T Izu
- Faculty of Pharmacy, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Ye Chen-Izu
- Faculty of Pharmacy, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Department of Biomedical Engineering, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 2303, Davis, CA 95616, USA; Department of Internal Medicine, Division of Cardiology, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 6315, Davis, CA 95616, USA
| | - Tamás Bányász
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - János Magyar
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - László Csernoch
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
| | - Péter P Nánási
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary.
| | - Norbert Szentandrássy
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary; Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, H-4012 Debrecen, Hungary
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Huang H, Pugsley MK, Fermini B, Curtis MJ, Koerner J, Accardi M, Authier S. Cardiac voltage-gated ion channels in safety pharmacology: Review of the landscape leading to the CiPA initiative. J Pharmacol Toxicol Methods 2017; 87:11-23. [PMID: 28408211 DOI: 10.1016/j.vascn.2017.04.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 03/27/2017] [Accepted: 04/06/2017] [Indexed: 12/15/2022]
Abstract
Voltage gated ion channels are central in defining the fundamental properties of the ventricular cardiac action potential (AP), and are also involved in the development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion currents, including the Na+ current (INa), L-type Ca2+ current (Ica-L), and K+ currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and S7B over a decade ago, there has been a focus on drug effects on QT prolongation clinically, and on the rapidly activating delayed rectifier current (IKr), nonclinically, for evaluation of proarrhythmic risk. This focus on QT interval prolongation and a single ionic current likely impacted negatively some drugs that lack proarrhythmic liability in humans. To rectify this issue, the Comprehensive in vitro proarrhythmia assay (CiPA) initiative has been proposed to integrate drug effects on multiple cardiac ionic currents with in silico modelling of human ventricular action potentials, and in vitro data obtained from human stem cell-derived ventricular cardiomyocytes to estimate proarrhythmic risk of new drugs with improved accuracy. In this review, we present the physiological functions and the molecular basis of major cardiac ion channels that contribute to the ventricle AP, and discuss the CiPA paradigm in drug development.
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Affiliation(s)
- Hai Huang
- CiToxLAB North America, 445, Armand-Frappier Boul, Laval H7V 4B3, QC, Canada
| | - Michael K Pugsley
- Department of Toxicology, Purdue Pharma L.P., Cranbury, NJ 08512, USA
| | | | - Michael J Curtis
- Cardiovascular Division, Faculty of Life Sciences & Medicine, King's College London, Rayne Institute, St Thomas' Hospital, London SE17EH, UK
| | - John Koerner
- Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA
| | - Michael Accardi
- CiToxLAB North America, 445, Armand-Frappier Boul, Laval H7V 4B3, QC, Canada
| | - Simon Authier
- CiToxLAB North America, 445, Armand-Frappier Boul, Laval H7V 4B3, QC, Canada.
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