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Lampert R, Day S, Ainsworth B, Burg M, Marino BS, Salberg L, Tome Esteban MT, Abrams DJ, Aziz PF, Barth C, Behr ER, Bell C, Berul CI, Bos JM, Bradley D, Cannom DS, Cannon BC, Concannon MA, Cerrone M, Czosek RJ, Dubin AM, Dziura J, Erickson CC, Estes NAM, Etheridge SP, Goldenberg I, Gray B, Haglund-Turnquist C, Harmon K, James CA, Johnsrude C, Kannankeril P, Lara A, Law IH, Li F, Link MS, Molossi SM, Olshansky B, Noseworthy PA, Saarel EV, Sanatani S, Shah M, Simone L, Skinner J, Tomaselli GF, Ware JS, Webster G, Zareba W, Zipes DP, Ackerman MJ. Vigorous Exercise in Patients With Congenital Long QT Syndrome: Results of the Prospective, Observational, Multinational LIVE-LQTS Study. Circulation 2024; 150:516-530. [PMID: 39051104 DOI: 10.1161/circulationaha.123.067590] [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: 10/13/2023] [Accepted: 05/31/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664.
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Affiliation(s)
- Rachel Lampert
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
| | - Sharlene Day
- University of Pennsylvania, Philadelphia (S.D.)
- University of Michigan Hospital, Ann Arbor (S.D., M.A.C.)
| | - Barbara Ainsworth
- School of Exercise and Health, Shanghai University of Sport, China (B.A.)
- College of Health Solutions/Arizona State University, Phoenix (B.A.)
| | - Matthew Burg
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
- VA Hospital, West Haven, CT (M.B.)
| | - Bradley S Marino
- Cleveland Clinic, OH (B.S.M., P.F.A.)
- Lurie Children's Hospital, Chicago, IL (B.S.M., G.W.)
| | - Lisa Salberg
- Hypertrophic Cardiomyopathy Association, Denville, NJ (L.S.)
| | - Maria Teresa Tome Esteban
- Cardiology Section, Cardiovascular and Genomics Research Institute, St. George's, University of London, UK (M.T.T.E., E.R.B.)
- Cardiology Department, St. George's University Hospitals NHS Foundation Trust, London, UK (M.T.T.E., E.R.B.)
| | | | | | - Cheryl Barth
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
| | - Elijah R Behr
- Cardiology Section, Cardiovascular and Genomics Research Institute, St. George's, University of London, UK (M.T.T.E., E.R.B.)
- Cardiology Department, St. George's University Hospitals NHS Foundation Trust, London, UK (M.T.T.E., E.R.B.)
| | - Cheyanne Bell
- Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN (C. Bell, J.M.B., B.C.C., C.H.-T., M.J.A.)
| | | | - Johan M Bos
- Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN (C. Bell, J.M.B., B.C.C., C.H.-T., M.J.A.)
| | | | | | - Bryan C Cannon
- Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN (C. Bell, J.M.B., B.C.C., C.H.-T., M.J.A.)
| | | | - Marina Cerrone
- Leon H. Charney Division of Cardiology, NYU Grossman Sch of Medicine, New York (M.C.)
| | - Richard J Czosek
- The Heart Institute, Cincinnati Children's Hospital Med Center, OH (R.J.C.)
| | - Anne M Dubin
- Stanford University School of Medicine, Palo Alto, CA (A.M.D.)
| | - James Dziura
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
| | | | - N A Mark Estes
- Tufts Medical Center, Boston, MA (N.A.M.E., M.S.L.)
- UPMC, Pittsburgh, PA (N.A.M.E.)
| | | | - Ilan Goldenberg
- Division of Cardiology, University of Rochester Medical Center, NY (I.G., W.Z.)
| | - Belinda Gray
- Faculty of Medicine and Health, University of Sydney/Royal Prince Alfred Hospital, Australia (B.G.)
| | - Carla Haglund-Turnquist
- Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN (C. Bell, J.M.B., B.C.C., C.H.-T., M.J.A.)
| | - Kimberly Harmon
- Department of Family Medicine, University of Washington, Seattle (K.H.)
| | | | | | - Prince Kannankeril
- Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt and Vanderbilt University, Nashville, TN (P.K.)
| | - Alice Lara
- Sudden Arrhythmia Death Syndrome Foundation, Salt Lake City, UT (A.L.)
| | - Ian H Law
- University of Iowa Carver College of Medicine, Iowa City (I.H.L., B.O.)
| | - Fangyong Li
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
| | - Mark S Link
- Tufts Medical Center, Boston, MA (N.A.M.E., M.S.L.)
- UT Southwestern Medical Center, Dallas, TX (M.S.L.)
| | - Silvana M Molossi
- Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston (S.M.M.)
| | - Brian Olshansky
- University of Iowa Carver College of Medicine, Iowa City (I.H.L., B.O.)
| | | | - Elizabeth V Saarel
- St. Lukes Medical Center/Primary Children's Hospital, Boise, ID (E.V.S.)
| | - Shubhayan Sanatani
- Institution British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada (S.S.)
| | - Maully Shah
- University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia (M.S.)
| | - Laura Simone
- Yale School of Medicine, New Haven, CT (R.L., M.B., C. Barth, J.D., F.L, L.S.)
| | - Jonathan Skinner
- Cardiac Inherited Disease Group, Starship Children's Hospital, Auckland, New Zealand (J.S.)
| | - Gordon F Tomaselli
- Johns Hopkins University, Baltimore, MD (C.A.J.,G.F.T.)
- Albert Einstein College of Medine, Bronx, NY (G.F.T.)
| | - James Simon Ware
- National Heart & Lung Inst & MRC London Institute of Medical Sciences, Imperial College London, UK (J.S.W.)
- Royal Brompton & Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK (J.S.W.)
| | | | - Wojciech Zareba
- Division of Cardiology, University of Rochester Medical Center, NY (I.G., W.Z.)
| | | | - Michael J Ackerman
- Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental Therapeutics; Divisions of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, MN (C. Bell, J.M.B., B.C.C., C.H.-T., M.J.A.)
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Theisen B, Holtz A, Rajagopalan V. Noncoding RNAs and Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Cardiac Arrhythmic Brugada Syndrome. Cells 2023; 12:2398. [PMID: 37830612 PMCID: PMC10571919 DOI: 10.3390/cells12192398] [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: 07/22/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/14/2023] Open
Abstract
Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.
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Affiliation(s)
- Benjamin Theisen
- Department of Biomedical and Anatomical Sciences, New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR 72401, USA
| | - Austin Holtz
- Department of Biomedical and Anatomical Sciences, New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR 72401, USA
| | - Viswanathan Rajagopalan
- Department of Biomedical and Anatomical Sciences, New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR 72401, USA
- Arkansas Biosciences Institute, Jonesboro, AR 72401, USA
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Nagy N, Tóth N, Nánási PP. Antiarrhythmic and Inotropic Effects of Selective Na +/Ca 2+ Exchanger Inhibition: What Can We Learn from the Pharmacological Studies? Int J Mol Sci 2022; 23:ijms232314651. [PMID: 36498977 PMCID: PMC9736231 DOI: 10.3390/ijms232314651] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/25/2022] Open
Abstract
Life-long stable heart function requires a critical balance of intracellular Ca2+. Several ion channels and pumps cooperate in a complex machinery that controls the influx, release, and efflux of Ca2+. Probably one of the most interesting and most complex players of this crosstalk is the Na+/Ca2+ exchanger, which represents the main Ca2+ efflux mechanism; however, under some circumstances, it can also bring Ca2+ into the cell. Therefore, the inhibition of the Na+/Ca2+ exchanger has emerged as one of the most promising possible pharmacological targets to increase Ca2+ levels, to decrease arrhythmogenic depolarizations, and to reduce excessive Ca2+ influx. In line with this, as a response to increasing demand, several more or less selective Na+/Ca2+ exchanger inhibitor compounds have been developed. In the past 20 years, several results have been published regarding the effect of Na+/Ca2+ exchanger inhibition under various circumstances, e.g., species, inhibitor compounds, and experimental conditions; however, the results are often controversial. Does selective Na+/Ca2+ exchanger inhibition have any future in clinical pharmacological practice? In this review, the experimental results of Na+/Ca2+ exchanger inhibition are summarized focusing on the data obtained by novel highly selective inhibitors.
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Affiliation(s)
- Norbert Nagy
- ELKH-SZTE Research Group of Cardiovascular Pharmacology, 6720 Szeged, Hungary
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary
- Correspondence: ; Tel.: +36-62-545-682; Fax: +36-62-545-680
| | - Noémi Tóth
- ELKH-SZTE Research Group of Cardiovascular Pharmacology, 6720 Szeged, Hungary
| | - Péter P. Nánási
- Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
- Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary
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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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Mareddy C, ScM MT, McDaniel G, Monfredi O. Exercise in the Genetic Arrhythmia Syndromes - A Review. Clin Sports Med 2022; 41:485-510. [PMID: 35710274 DOI: 10.1016/j.csm.2022.02.008] [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] [Indexed: 11/15/2022]
Abstract
Provide a brief summary of your article (100-150 words; no references or figures/tables). The synopsis appears only in the table of contents and is often used by indexing services such as PubMed. Genetic arrhythmia syndromes are rare, yet harbor the potential for highly consequential, often unpredictable arrhythmias or sudden death events. There has been historical uncertainty regarding the correct advice to offer to affected patients who are reasonably wanting to participate in sporting and athletic endeavors. In some cases, this had led to abundantly cautious disqualifications, depriving individuals from participation unnecessarily. Societal guidance and expert opinion has evolved significantly over the last decade or 2, along with our understanding of the genetics and natural history of these conditions, and the emphasis has switched toward shared decision making with respect to the decision to participate or not, with patients and families becoming better informed, and willing participants in the decision making process. This review aims to give a brief update of the salient issues for the busy physician concerning these syndromes and to provide a framework for approaching their management in the otherwise aspirational or keen sports participant.
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Affiliation(s)
- Chinmaya Mareddy
- Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, 1215 Lee St, Charlottesville, VA 22908, USA
| | - Matthew Thomas ScM
- Department of Pediatrics, P.O. Box 800386, Charlottesville, VA 22908, USA
| | - George McDaniel
- Department of Pediatric Cardiology, Battle Building 6th Floor, 1204 W. Main St, Charlottesville, VA 22903, USA
| | - Oliver Monfredi
- Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, 1215 Lee St, Charlottesville, VA 22908, USA.
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The relationship between vitamin B12 levels and electrocardiographic ventricular repolarization markers. NUTR HOSP 2022; 39:588-593. [PMID: 35485384 DOI: 10.20960/nh.03995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND it has been shown that vitamin B12 deficiency, which can cause hematological and neuropsychiatric disorders, may also be associated with cardiac autonomic dysfunction, heart rate variability, endothelial dysfunction, and a decrease in myocardial deformation. AIMS the aim of our study is to evaluate the relationship between vitamin B12 levels and electrocardiographic repolarization disorders, which are indicators of arrhythmogenic predisposition in healthy individuals. METHODS our study population consisted of 214 healthy adults. Considering the distribution of vitamin B12 levels and accepting 25 % and 75 % percentiles as the cut-off values, the participants were divided into 3 groups. Laboratory, echocardiography and electrocardiography (ECG) measurements were compared between three groups. ECG measurements were performed manually and Tpeak-Tend (Tp-e), Tp-e corrected (Tp-ec), QT and QT corrected (QTc) intervals were calculated. RESULTS the patients in Group 1 (vitamin B12 < 253 pg/ml) were found to have significantly higher QT and QTc dispersions, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios when compared to those in Group 2 (253 pg/ml < vitamin B12 > 436 pg/ml) and Group 3 (vitamin B12 > 436 pg/ml). On the other hand, a negative significant correlation was detected between vitamin B12 levels and Tp-e, Tp-e/QT, Tp-e/QTc ratios, QT and QTc dispersions. CONCLUSION a low level of vitamin B12 in healthy individuals can be a significant indicator of arrhythmogenic susceptibility. A close follow-up of these subjects in terms of arrhythmogenic predisposition can be useful.
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Kui P, Polyák A, Morvay N, Tiszlavicz L, Nagy N, Ördög B, Takács H, Leprán I, Farkas A, Papp JG, Jost N, Varró A, Baczkó I, Farkas AS. Long-Term Endurance Exercise Training Alters Repolarization in a New Rabbit Athlete’s Heart Model. Front Physiol 2022; 12:741317. [PMID: 35237176 PMCID: PMC8882986 DOI: 10.3389/fphys.2021.741317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/22/2021] [Indexed: 11/13/2022] Open
Abstract
In the present study, the effect of long-term exercise training was investigated on myocardial morphological and functional remodeling and on proarrhythmic sensitivity in a rabbit athlete’s heart model. New-Zealand white rabbits were trained during a 12-week long treadmill running protocol and compared with their sedentary controls. At the end of the training protocol, echocardiography, in vivo and in vitro ECG recordings, proarrhythmic sensitivity with dofetilide (nM) were performed in isolated hearts, and action potential duration (APD) measurements at different potassium concentrations (4.5 and 2 mM) were made in the isolated papillary muscles. Expression levels of the slow component of delayed rectifier potassium current and fibrosis synthesis and degradation biomarkers were quantified. Echocardiography showed a significantly dilated left ventricle in the running rabbits. ECG PQ and RR intervals were significantly longer in the exercised group (79 ± 2 vs. 69 ± 2 ms and 325 ± 11 vs. 265 ± 6 ms, p < 0.05, respectively). The in vivo heart rate variability (HRV) (SD of root mean square: 5.2 ± 1.4 ms vs. 1.4 ± 0.2 ms, p < 0.05) and Tpeak-Tend variability were higher in the running rabbits. Bradycardia disappeared in the exercised group in vitro. Dofetilide tended to increase the QTc interval in a greater extent, and significantly increased the number of arrhythmic beats in the trained animals in vitro. APD was longer in the exercised group at a low potassium level. Real-time quantitative PCR (RT-qPCR) showed significantly greater messenger RNA expression of fibrotic biomarkers in the exercised group. Increased repolarization variability and higher arrhythmia incidences, lengthened APD at a low potassium level, increased fibrotic biomarker gene expressions may indicate higher sensitivity of the rabbit “athlete’s heart” to life-threatening arrhythmias.
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Affiliation(s)
- Péter Kui
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Alexandra Polyák
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- Department of Internal Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- ELKH-SZTE Working Group of Cardiovascular Pharmacology, Szeged, Hungary
| | - Nikolett Morvay
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - László Tiszlavicz
- Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Norbert Nagy
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- ELKH-SZTE Working Group of Cardiovascular Pharmacology, Szeged, Hungary
| | - Balázs Ördög
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Hedvig Takács
- Department of Internal Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - István Leprán
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - András Farkas
- Department of Internal Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Julius Gy. Papp
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- ELKH-SZTE Working Group of Cardiovascular Pharmacology, Szeged, Hungary
| | - Norbert Jost
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- ELKH-SZTE Working Group of Cardiovascular Pharmacology, Szeged, Hungary
| | - András Varró
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- ELKH-SZTE Working Group of Cardiovascular Pharmacology, Szeged, Hungary
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- *Correspondence: András Varró,
| | - István Baczkó
- Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Attila S. Farkas
- Department of Internal Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
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Electrocardiographic data of children with type 1 diabetes mellitus. Cardiol Young 2022; 32:106-110. [PMID: 34724995 DOI: 10.1017/s1047951121004376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Adult patients diagnosed with type 1 diabetes mellitus are at risk for ventricular arrhythmias and sudden cardiac death. AIM The objective of our study is to evaluate the electrocardiographic data of children diagnosed with type 1 diabetes mellitus and to determine the possibility of arrhythmia in order to prevent sudden death. METHODS Electrocardiographic data of 60 patients diagnosed with type 1 diabetes mellitus and 86 controls, who were compatible with the patient group in terms of age and gender, were compared. RESULTS The duration of diabetes in our patients with type 1 diabetes mellitus was 5.23 ± 1.76 years, and the haemoglobin A1c levels were 9.63% ± 1.75%. The heart rate, QRS, QT maximum, QT dispersion, QTc minimum, QTc maximum, QTc dispersion, Tp-e maximum, Tp-e maximum/QTc maximum and the JTc were significantly higher compared to the control group. There was no significant correlation between the duration of type 1 diabetes mellitus and HbA1c levels and the electrocardiographic data. CONCLUSION We attributed the lack of a significant correlation between the duration of type 1 diabetes mellitus and the haemoglobin A1c levels and the electrocardiographic data to the fact that the duration of diabetes was short, since our patients were children. We believe that patients with type 1 diabetes mellitus should be followed up closely in terms of sudden death, as they have electrocardiographic changes that may cause arrhythmias compared to the control group. However, more studies with longer follow-up periods are necessary to support our data.
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Kani K, Fujiu K. Electrical Storm. Int Heart J 2021; 62:1195-1198. [PMID: 34853216 DOI: 10.1536/ihj.21-662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Kunihiro Kani
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
| | - Katsuhito Fujiu
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
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10
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Ellermann C, Wolfes J, Eckardt L, Frommeyer G. Role of the rabbit whole-heart model for electrophysiologic safety pharmacology of non-cardiovascular drugs. Europace 2021; 23:828-836. [PMID: 33200170 DOI: 10.1093/europace/euaa288] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 08/27/2020] [Indexed: 11/13/2022] Open
Abstract
Plenty of non-cardiovascular drugs alter cardiac electrophysiology and may ultimately lead to life-threatening arrhythmias. In clinical practice, measuring the QT interval as a marker for the repolarization period is the most common tool to assess the electrophysiologic safety of drugs. However, the sole measurement of the QT interval may be insufficient to determine the proarrhythmic risk of non-cardiovascular agents. Several other markers are considered in pre-clinical safety testing to determine potential harm on cardiac electrophysiology. Besides measuring typical electrophysiologic parameters such as repolarization duration, whole-heart models allow the determination of potential predictors for proarrhythmia. Spatial and temporal heterogeneity as well as changes of shape of the action potential can be easily assessed. In addition, provocation manoeuvers (either by electrolyte imbalances or programmed pacing protocols) may induce sustained arrhythmias and thereby determine ventricular vulnerability to arrhythmias. Compared with the human heart, the rabbit heart possesses a similar distribution of ion currents that govern cardiac repolarization, resulting in a rectangular action potential configuration in both species. In addition, similar biophysical properties of rabbit and human cardiac ion channels lead to a comparable pharmacologic response in human and rabbit hearts. Of note, arrhythmia patterns resemble in both species due to the similar effective size of human and rabbit hearts. Thus, the rabbit heart is particularly suitable for testing the electrophysiologic safety of drugs. Several experimental setups have been developed for studying cardiac electrophysiology in rabbits, ranging from single cell to tissue preparations, whole-heart setups, and in vivo models.
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Affiliation(s)
- Christian Ellermann
- Department of Cardiology II (Electrophysiology), University Hospital Münster, Albert-Schweitzer-Campus 1, Münster D-48149, Germany
| | - Julian Wolfes
- Department of Cardiology II (Electrophysiology), University Hospital Münster, Albert-Schweitzer-Campus 1, Münster D-48149, Germany
| | - Lars Eckardt
- Department of Cardiology II (Electrophysiology), University Hospital Münster, Albert-Schweitzer-Campus 1, Münster D-48149, Germany
| | - Gerrit Frommeyer
- Department of Cardiology II (Electrophysiology), University Hospital Münster, Albert-Schweitzer-Campus 1, Münster D-48149, Germany
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11
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Proshlyakov AY, Chomakhidze PS, Novikova NA. Comparative Characteristics of Beta-Blockers in Patients with Congenital Long QT Syndrome. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2021. [DOI: 10.20996/1819-6446-2021-06-19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Congenital long QT syndrome is a pathology that requires special attention and knowledge about the safety and effectiveness of various medications. Prolongation of the QT interval due to congenital or acquired causes is an important factor in the development of an unfavorable life forecast with the formation of an elongated QT syndrome. With an unfavorable course, patients suffer from loss of consciousness, episodes of tachycardia. Often, stable polymorphic ventricular tachycardia develops. The risk of sudden cardiac death in this pathology can vary from 0.33% to 5%. In people who have suffered an episode of cardiac arrest, and do not have a permanent prescribed antiarrhythmic therapy, the mortality rate reaches 50% within 15 years. Preventive administration of antiarrhythmic drugs is not always effective. A positive result of treatment depends on the severity of long QT syndrome and its genotype. Beta-blockers are often prescribed to patients of different ages with various cardiac pathologies, including for the prevention of arrhythmia in long QT syndrome. Beta-blockers differ in various pharmacokinetic and pharmacodynamic parameters (lipophilicity/hydrophilicity, selectivity, presence/absence of internal sympathomimetic activity), which, along with the variant of the disease genotype, can affect their effectiveness and safety in the considered pathology. This review article presents the results of major studies on the safety and effectiveness of different groups of beta blockers in various variants of long QT syndrome. The preferred beta-blockers for various genotypes of the syndrome were determined, and a comparative characteristic of beta-blockers for their safety and preventive effectiveness was given.
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Affiliation(s)
- A. Yu. Proshlyakov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - P. Sh. Chomakhidze
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - N. A. Novikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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12
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Effects of treatment with hydroxychloroquine and azithromycin on the index of cardiac electrophysiological balance in patients with COVID-19: A retrospective cohort study. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.843042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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13
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Tp-Te interval prolongs in hypertension independent of the left ventricular geometry. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.754891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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14
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Akkuş A, Belviranli M, Şap F, Okudan N. Assessment of Structure, Function, and Rhythm of the Heart with Echocardiography and Electrocardiography in Adolescent Swimmers. Pediatr Cardiol 2021; 42:182-188. [PMID: 32965565 DOI: 10.1007/s00246-020-02469-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 09/18/2020] [Indexed: 01/20/2023]
Abstract
The aim of this study was to evaluate the cardiac parameters by using electrocardiography and echocardiography in adolescent swimmers. Twenty-two adolescent swimmers and 22 gender- and age-matched sedentary controls admitted to our center between November 2018 and May 2019 were included in this study. In addition to demographical characteristics, participants were assessed via a 12-lead electrocardiography and two-dimensional echocardiography for cardiac function. On the echocardiography, end-systolic and end-diastolic interventricular septum, end-systolic and end-diastolic left ventricular posterior wall thicknesses, left atrial width, Tricuspid E, left ventricular mass and left ventricular mass index were higher in the swimmers when compared to the sedentary controls (P < 0.05). On the electrocardiography, Tp-e duration which reflects ventricular transmural repolarization, and Tp-e/QT and Tp-e/corrected QT ratios were higher in the swimmers than the sedentary controls (P < 0.05). In conclusion, swimming exercise in children leads to concentric thickening of left ventricle and induces an increase in Tp-e duration, and Tp-e/QT and Tp-e/corrected QT ratios, which are the novel markers for risk of ventricular arrhythmias.
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Affiliation(s)
- Abdullah Akkuş
- Department of Paediatrics, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Muaz Belviranli
- Division of Sports Physiology, Department of Physiology, Faculty of Medicine, Selçuk University, 42131, Konya, Turkey.
| | - Fatih Şap
- Division of Paediatric Cardiology, Department of Paediatrics, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Nilsel Okudan
- Division of Sports Physiology, Department of Physiology, Faculty of Medicine, Selçuk University, 42131, Konya, Turkey
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15
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Yenerçağ M, Arslan U, Doğduş M, Günal Ö, Öztürk ÇE, Aksan G, Erdoğan G, Gül S, Yontar OC, Şen A. Evaluation of electrocardiographic ventricular repolarization variables in patients with newly diagnosed COVID-19. J Electrocardiol 2020; 62:5-9. [PMID: 32731139 PMCID: PMC7373019 DOI: 10.1016/j.jelectrocard.2020.07.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/08/2020] [Accepted: 07/17/2020] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has spread rapidly. COVID-19 has been associated with a number of cardiovascular complications, including arrhythmias. The mechanism of ventricular arrhythmias in patients with COVID-19 is uncertain. The aim of the present study was to evaluate the ventricular repolarization by using the Tp-e interval, QT dispersion, Tp-e/QT ratio, and Tp-e/QTc ratio as candidate markers of ventricular arrhythmias in patients with newly diagnosed COVID-19. In addition, the relationship between the repolarization parameters and the CRP (C-reactive protein) was investigated. METHODS 75 newly diagnosed COVID-19 patients, 75 age and sex matched healthy subjects were included in the study between 20th March 2020 and 10th April 2020. The risk of ventricular arrhythmias was evaluated by calculating the electrocardiographic Tp-e and QT interval, Tp-e dispersion, corrected QT(QTc), QT dispersion (QTd), corrected QTd, Tp-e/QT and Tp-e/QTc ratios. CRP values were also measured in patients with newly diagnosed COVID-19. RESULTS Tp-e interval (80.7 ± 4.6 vs. 70.9 ± 4.8; p < .001), Tp-e / QT ratio (0.21 ± 0.01 vs. 0.19 ± 0.01; p < .001) and Tp-e/QTc ratio (0.19 ± 0.01 vs.0.17 ± 0.01; p < .001) were significantly higher in patients with newly diagnosed COVID-19 than the control group. There was a significant positive correlation between Tp-e interval, Tp-e/QTc ratio and CRP in patients with newly diagnosed COVID-19 (rs = 0.332, p = .005, rs = 0.397, p < .001 consecutively). During their treatment with hydroxychloroquine (HCQ), azithromycin and favipiravir, ventricular tachycardia episodes were observed in in two COVID-19 patients during their hospitalization in the intensive care unit. CONCLUSION Our study showed for the first time in literature that the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio, which are evaluated electrocardiographically in patients with newly diagnosed COVID-19, were prolonged compared with normal healthy individuals. A positive correlation was determined between repolarization parameters and CRP. We believe that pre-treatment evaluation of repolarization parameters in newly diagnosed COVID-19 would be beneficial for predicting ventricular arrhythmia risk.
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Affiliation(s)
- Mustafa Yenerçağ
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Uğur Arslan
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey.
| | - Mustafa Doğduş
- Department of Cardiology, University of Usak Training and Research Hospital, Usak, Turkey
| | - Özgür Günal
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Çağatay Erman Öztürk
- Department of of Anaesthesiology and Reanimation, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Gökhan Aksan
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Güney Erdoğan
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Sefa Gül
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Osman Can Yontar
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
| | - Ahmet Şen
- Department of of Anaesthesiology and Reanimation, University of Health Sciences Samsun Training and Research Hospital, Samsun, Turkey
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Abstract
The main inherited cardiac arrhythmias are long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. These rare diseases are often the underlying cause of sudden cardiac death in young individuals and result from mutations in several genes encoding ion channels or proteins involved in their regulation. The genetic defects lead to alterations in the ionic currents that determine the morphology and duration of the cardiac action potential, and individuals with these disorders often present with syncope or a life-threatening arrhythmic episode. The diagnosis is based on clinical presentation and history, the characteristics of the electrocardiographic recording at rest and during exercise and genetic analyses. Management relies on pharmacological therapy, mostly β-adrenergic receptor blockers (specifically, propranolol and nadolol) and sodium and transient outward current blockers (such as quinidine), or surgical interventions, including left cardiac sympathetic denervation and implantation of a cardioverter-defibrillator. All these arrhythmias are potentially life-threatening and have substantial negative effects on the quality of life of patients. Future research should focus on the identification of genes associated with the diseases and other risk factors, improved risk stratification and, in particular for Brugada syndrome, effective therapies.
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17
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Güney AY, Şap F, Eklioğlu BS, Oflaz MB, Atabek ME, Baysal T. Investigation of the effect of epicardial adipose tissue thickness on cardiac conduction system in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2020; 33:713-720. [PMID: 32441671 DOI: 10.1515/jpem-2020-0001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 03/15/2020] [Indexed: 11/15/2022]
Abstract
Objectives Investigation of the association between epicardial adipose tissue thickness (EATT) and P-wave dispersion (Pd), QT dispersion (QTd), corrected QT dispersion (QTcd) and Tp-e interval in children with Type 1 Diabetes Mellitus (T1DM) was aimed. Methods Forty-one children with T1DM and 41 age- and gender-matched healthy children were included in the study. Demographical characteristics of all cases were examined. In echocardiography; in addition to conventional echocardiographic measurements, end-systolic EATT was measured from right ventricular free wall. In electrocardiogram; Pd, QTd, QTcd and Tp-e interval durations, as well as Tp-e/QT and Tp-e/QTc ratios were calculated. Correlation values between EATT and electrocardiographic parameters were also noted. Results Mean age of the patient group was determined to be 12.43 ± 3.04 years and that of the control group was determined to be 12.08 ± 2.56 years. There was no significant difference between the groups in regard to age, gender, body weight, height and body mass index. In the patient group; EATT, Pd, QTd, QTcd and Tp-e interval were determined to be significantly higher compared to the control group. In the patient group, no significant correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. However, when both patient and control groups were evaluated together, a statistically significant positive correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. Conclusions In children with T1DM, an increase in epicardial adipose tissue thickness and in risk of cardiac arrhythmias has been demonstrated. To reveal the possible unfavorable effects of EATT on cardiac conduction system in T1DM patients needs further studies.
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Affiliation(s)
- Ahmet Yasin Güney
- Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Fatih Şap
- Division of Pediatric Cardiology, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Akyokus-Meram, Konya, 42080, Turkey
| | - Beray Selver Eklioğlu
- Division of Pediatric Endocrinology, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Mehmet Burhan Oflaz
- Division of Pediatric Cardiology, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Mehmet Emre Atabek
- Division of Pediatric Endocrinology, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Tamer Baysal
- Division of Pediatric Cardiology, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
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18
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Safaeian R, Hassani V, Asghari A, Mohseni M, Ashraf H, Koleini ZS. The effects of ondansetron versus dexamethasone on electrocardiographic markers of ventricular repolarization in children undergoing cochlear implant. Int J Pediatr Otorhinolaryngol 2020; 132:109896. [PMID: 32032916 DOI: 10.1016/j.ijporl.2020.109896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/06/2020] [Accepted: 01/18/2020] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Congenital hearing loss is associated with cardiac rhythm disturbances namely long Q-T syndrome. This study was designed to investigate the effect of anti-emetic doses of ondansetron and dexamethasone on ECG recordings in children undergoing cochlear implant surgery. METHODS Sixty-three pediatric patients scheduled for elective cochlear implantation were enrolled in the study. Two patients were excluded as their baseline ECG showed long QT syndrome. Anesthesia was induced with fentanyl, propofol and atracurium and maintained with propofol. Dexamethasone 0.1 mg.kg-1or ondansetron 0.2 mg.kg-1was randomly administered for the participants approximately 30 min before the end of surgery. ECG recording was performed 15 min after induction of anesthesia and 15 min after dexamethasone/ondansetron administration. RR interval, QRS duration, QT interval, and Tp-e interval were measured by a blinded cardiologist. RESULTS Ondansetron resulted in no significant changes in RR, JTc and QTc intervals; while prolongedTp-e interval. Multivariable logistic regression analysis showed that use of ondansetron was an independent predictor of QTc prolongation after adjustment for age, gender and baseline QTc (OR = 17.94, CI 95% 1.97-168.70, p = 0.011). The incidence of postoperative retching/vomiting in ondansetron group was significantly lower than dexamethasone group. (3.2% vs. 26.7%, p = 0.011). CONCLUSION The risk of arrhythmias with the use of ondansetron in otherwise healthy candidates of cochlear implant is very low. However, the drug may induce significant changes in ECG parameters. The clinical significance of these changes in patients with cardiac conduction abnormalities should be investigated in further studies.
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Affiliation(s)
- Reza Safaeian
- Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran
| | - Valiollah Hassani
- Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran
| | - Alimohamad Asghari
- Skull Base Research Center, The Five Senses Health Research Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Masood Mohseni
- Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran.
| | - Haleh Ashraf
- Cardiac Primary Prevention Research Center (CPPRC), Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Sadat Koleini
- Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran
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Inanır M, Gunes Y, Sincer I, Erdal E. Evaluation of Electrocardiographic Ventricular Depolarization and Repolarization Variables in Type 1 Diabetes Mellitus. Arq Bras Cardiol 2020; 114:275-280. [PMID: 32215498 PMCID: PMC7077569 DOI: 10.36660/abc.20180343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 03/10/2019] [Indexed: 12/14/2022] Open
Abstract
Background The risk of cardiovascular events and sudden death increases with type 1 diabetes mellitus (T1DM). Objective To evaluate electrocardiographic markers of arrhythmias in T1DM patients. Methods Electrocardiographic parameters reflecting ventricular depolarization and repolarization, namely, QT, QTc, QTd, QTdc, Tp-e, JT, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios, of 46 patients diagnosed with T1DM were retrospectively analyzed and compared with 46 healthy age-, sex-, and body mass-matched controls. Correlations between T1DM duration, hemoglobin A1c (HbA1c), and ventricular repolarization variables were analyzed. P values lower than 0.05 were considered statistically significant. Results Diabetes duration was 16.6 ± 7.1 years, and HbA1c was 10.81% ± 3.27% in the T1DM group. In comparison with the control group, heart rate, QTc, QTd, QTdc, Tp-e and JTc intervals, Tp-e/QT ratio (p < 0.001), and Tp-e/QTc ratio (p = 0.007) were significantly higher in T1DM patients. T1DM duration and HbA1c levels were significantly correlated with QTc, QTd, QTdc, Tp-e, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios. Conclusions In T1DM patients, potential electrocardiographic repolarization predictors were significantly increased in correlation with disease duration and HbA1c levels. These findings may contribute to the understanding of sudden cardiac death in patients with T1DM.
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Affiliation(s)
- Mehmet Inanır
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Yilmaz Gunes
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Isa Sincer
- Abant Izzet Baysal University Hospital, Bolu - Turkey
| | - Emrah Erdal
- Abant Izzet Baysal University Hospital, Bolu - Turkey
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20
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Vehmeijer JT, Koyak Z, Vink AS, Budts W, Harris L, Silversides CK, Oechslin EN, Zwinderman AH, Mulder BJM, de Groot JR. Prolonged T peak -T end interval is a risk factor for sudden cardiac death in adults with congenital heart disease. CONGENIT HEART DIS 2019; 14:952-957. [PMID: 31573144 PMCID: PMC7003836 DOI: 10.1111/chd.12847] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 09/05/2019] [Accepted: 09/11/2019] [Indexed: 11/29/2022]
Abstract
Objective Adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well‐defined. The Tpeak‐Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non‐ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients. Design From an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention. Outcome Measures TpTe was measured on a standard 12‐lead ECG. The maximum TpTe of all ECG leads (TpTe‐max), mean (TpTe‐mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis. Results ECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe‐max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe‐mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7‐12.4, P < .001). Conclusions The TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.
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Affiliation(s)
- Jim T Vehmeijer
- Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Zeliha Koyak
- Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - A Suzanne Vink
- Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Werner Budts
- Department of Cardiology, Universitair Ziekenhuis Leuven, Leuven, Belgium.,Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Louise Harris
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto Congenital Cardiac Centre for Adults, University of Toronto, Toronto, Ontario, Canada
| | - Candice K Silversides
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto Congenital Cardiac Centre for Adults, University of Toronto, Toronto, Ontario, Canada
| | - Erwin N Oechslin
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto Congenital Cardiac Centre for Adults, University of Toronto, Toronto, Ontario, Canada
| | - Aeilko H Zwinderman
- Department of Clinical Epidemiology and Biostatistics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Barbara J M Mulder
- Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.,Netherlands Heart Institute, Utrecht, the Netherlands
| | - Joris R de Groot
- Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
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Özbek SC, Sökmen E. Usefulness of Tp-Te interval and Tp-Te/QT ratio in the prediction of ventricular arrhythmias and mortality in acute STEMI patients undergoing fibrinolytic therapy. J Electrocardiol 2019; 56:100-105. [DOI: 10.1016/j.jelectrocard.2019.07.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 06/22/2019] [Accepted: 07/07/2019] [Indexed: 12/20/2022]
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22
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De Diego C, Zaballos M, Quintela O, Sevilla R, Callejo D, González-Panizo J, Anadón MJ, Almendral J. Bupivacaine Toxicity Increases Transmural Dispersion of Repolarization, Developing of a Brugada-like Pattern and Ventricular Arrhythmias, Which is Reversed by Lipid Emulsion Administration. Study in an Experimental Porcine Model. Cardiovasc Toxicol 2019; 19:432-440. [DOI: 10.1007/s12012-019-09515-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Inanir M, Sincer I, Erdal E, Gunes Y, Cosgun M, Mansiroglu AK. Evaluation of electrocardiographic ventricular repolarization parameters in extreme obesity. J Electrocardiol 2018; 53:36-39. [PMID: 30721839 DOI: 10.1016/j.jelectrocard.2018.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 11/10/2018] [Accepted: 12/05/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND AND OBJECTIVES The risk of sudden death and cardiac arrhythmia increases in morbidly obese patients. We aimed to evaluate the marker of arrhythmias such as Tp-e/QT, Tp-e/QTc, Tp-e/JT and Tp-e/JTc ratios in extreme obesity. METHODS The study included 41 extremely obese patients and 41 control subjects. QTmax, QTmin, QRS, JT and Tp-e intervals were measured od 12‑lead electrocardiographies. In addition, Tp-e/QT, Tp-e/QTc, Tp-e/JT and Tp-e/JTc rates and QTc, cQTd and JTc intervals were calculated. RESULTS Tp-e interval (79.2 ± 9.7 ms (milisecond) vs. 68.6 ± 8.1, p < 0.001), QTc interval (395.9 ± 18.8 vs. 377.9 ± 19.3 ms, p < 0.001), JTc interval (317.1 ± 27.0 vs. 297.4 ± 23.2 ms, p = 0.001), Tp-e/QT ratio (0.22 ± 0.03vs. 0.19 ± 0.02, p < 0.001), Tp-e/QTc ratio (0.20 ± 0.26vs. 0.18 ± 0.02, p = 0.001), Tp-e/JT ratio (0.29 ± 0.04 vs. 0.25 ± 0.03, p < 0.001), TPe/JTc ratio (0.25 ± 0.04 vs. 0.23 ± 0.03, p = 0.018), QTd (32.8 ± 10 vs.15 ± 6.4 ms, p < 0.001) and cQTd (70.0 ± 30.1 vs. 31.3 ± 22.4 ms, p < 0.001) were significantly higher in obese patients. CONCLUSION Compared to healthy subjects potential ECG repolarization predictors were significantly increased in extremely obese patients.
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Affiliation(s)
- M Inanir
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey.
| | - I Sincer
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey
| | - E Erdal
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey
| | - Y Gunes
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey
| | - M Cosgun
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey
| | - A K Mansiroglu
- Abant Izzet Baysal University, Medical Faculty, Cardiology Department, Bolu, Turkey
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Qiu B, Wang Y, Li C, Guo H, Xu Y. Utility of the JT Peak Interval and the JT Area in Determining the Proarrhythmic Potential of QT-Shortening Agents. J Cardiovasc Pharmacol Ther 2018; 24:160-171. [PMID: 30092655 DOI: 10.1177/1074248418791999] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Drug-induced long QT increases the risk of ventricular tachyarrhythmia known as torsades de pointes (TdP). Many biomarkers have been used to predict TdP. At present, however, there are few biomarkers for arrhythmias induced by QT-shortening drugs. The objective of the present study was to identify the best biomarkers for predicting arrhythmias caused by the 4 potassium channel openers ICA-105574, NS-1643, R-L3, and pinacidil. Our results showed that, at higher concentrations, all 4 potassium channel openers induced ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts, but not in rabbit hearts. The electrocardiography parameters were measured including QT/QTc, JT peak, Tp-e interval, JT area, short-term beat-to-beat QT interval variability (STV), and index of cardiac electrophysiological balance (iCEB). We found that the potassium channel openers at test concentrations shortened the QT/QTc and the JT peak interval and increased the JT area. Nevertheless, even at proarrhythmic concentrations, they did not always change STV, Tp-e, or iCEB. Receiver operating characteristic curve analysis showed that the JT peak interval representing the early repolarization phase and the JT area reflecting the dispersion of ventricular repolarization were the best predictors of VT/VF. Action potential recordings in guinea pig papillary muscle revealed that except for pinacidil, the potassium channel openers shortened APD30 in a concentration-dependent manner. They also evoked early or delayed afterdepolarizations at fast pacing rates. Patch-clamp recordings in guinea pig ventricular cardiomyocytes showed that the potassium channel openers enhanced the total outward currents during the early phase of action potential repolarization, especially at proarrhythmic concentrations. We concluded that the JT peak interval and the JT area are surrogate biomarkers identifying the risk of proarrhythmia associated with the administration of QT-shortening agents. The acceleration of early-phase repolarization and the increased dispersion of ventricular repolarization may contribute to the occurrence of arrhythmias.
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Affiliation(s)
- Bo Qiu
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, China.,The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.,The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei, China.,Hebei General Hospital, Shijiazhuang, China
| | - Yuhong Wang
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing, China
| | - Congxin Li
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, China.,The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.,The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei, China
| | - Huicai Guo
- Department of Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yanfang Xu
- Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, China.,The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, Hebei, China.,The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei, China
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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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Lester RM, Olbertz J. Early drug development: assessment of proarrhythmic risk and cardiovascular safety. Expert Rev Clin Pharmacol 2016; 9:1611-1618. [PMID: 27718759 DOI: 10.1080/17512433.2016.1245142] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION hERG assays and thorough ECG trials have been mandated since 2005 to evaluate the QT interval and potential proarrhythmic risk of new chemical entities. The high cost of these studies and the shortcomings inherent in these binary and limited approaches to drug evaluation have prompted regulators to search for more cost effective and mechanistic paradigms to assess drug liability as exemplified by the CiPA initiative and the exposure response ICH E14(R3) guidance document. Areas covered: This review profiles the changing regulatory landscape as it pertains to early drug development and outlines the analyses that can be performed to characterize preclinical and early clinical cardiovascular risk. Expert commentary: It is further acknowledged that the narrow focus on the QT interval needs to be expanded to include a more comprehensive evaluation of cardiovascular risk since unanticipated off target effects have led to the withdrawal of multiple drugs after they had been approved and marketed.
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Affiliation(s)
- Robert M Lester
- a Cardiovascular Safety Services , Celerion Inc. , Tempe , AZ , USA
| | - Joy Olbertz
- a Cardiovascular Safety Services , Celerion Inc. , Tempe , AZ , USA
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27
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Tse G, Liu T, Li KHC, Laxton V, Chan YWF, Keung W, Li RA, Yan BP. Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies. Front Physiol 2016; 7:467. [PMID: 27803673 PMCID: PMC5067537 DOI: 10.3389/fphys.2016.00467] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 09/27/2016] [Indexed: 12/19/2022] Open
Abstract
Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na+ channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na+, K+, Ca2+, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, 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 VT/VF. 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 and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.
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Affiliation(s)
- Gary Tse
- Department of Medicine and Therapeutics, Chinese University of Hong KongHong Kong, Hong Kong
- Li Ka Shing Institute of Health Sciences, Chinese University of Hong KongHong Kong, Hong Kong
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin, China
| | - Ka H. C. Li
- Faculty of Medicine, Newcastle UniversityNewcastle, UK
| | - Victoria Laxton
- Intensive Care Department, Royal Brompton and Harefield NHS TrustLondon, UK
| | - Yin W. F. Chan
- School of Biological Sciences, University of CambridgeCambridge, UK
| | - Wendy Keung
- Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong KongPokfulam, Hong Kong
| | - Ronald A. Li
- Ming Wai Lau Centre for Reparative Medicine, Karolinska InstitutetSolna, Sweden
| | - Bryan P. Yan
- Department of Medicine and Therapeutics, Chinese University of Hong KongHong Kong, Hong Kong
- Department of Epidemiology and Preventive Medicine, Monash UniversityMelbourne, VIC, Australia
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Alonso S, Bär M, Echebarria B. Nonlinear physics of electrical wave propagation in the heart: a review. REPORTS ON PROGRESS IN PHYSICS. PHYSICAL SOCIETY (GREAT BRITAIN) 2016; 79:096601. [PMID: 27517161 DOI: 10.1088/0034-4885/79/9/096601] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The beating of the heart is a synchronized contraction of muscle cells (myocytes) that is triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media with applications to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact for cardiac arrhythmias.
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Affiliation(s)
- Sergio Alonso
- Physikalisch-Technische Bundesanstalt, Abbestr. 2-12 10587, Berlin, Germany. Department of Physics, Universitat Politècnica de Catalunya, Av. Dr. Marañón 44, E-08028 Barcelona, Spain
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Abstract
The heartbeat originates within the sinoatrial node (SA node or SAN), a small highly specialized structure containing <10,000 genuine pacemaker cells. The ~5 billion working cardiomyocytes downstream of the SAN remain quiescent when it fails, leading to circulatory collapse and fueling a $6B/year electronic pacemaker industry. The electronic pacemaker devices work quite well. But, device-related problems persist. These include lead failure/repositioning, finite battery life, and infection. For pediatric patients, the children outgrow the length of the leads, necessitating replacement with longer leads. These pitfalls have motivated creation of biological pacing. that are free from all hardware. Toward this goal, we and others have tested the concept of biological pacemakers. Combined with efforts to create clinically relevant, large animal models of biological pacing, the field is moving beyond a conceptual novelty toward a future with clinical reality.
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Ashrafi R, Yon M, Pickavance L, Yanni Gerges J, Davis G, Wilding J, Jian K, Zhang H, Hart G, Boyett M. Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis. J Obes 2016; 2016:7127898. [PMID: 27747100 PMCID: PMC5056006 DOI: 10.1155/2016/7127898] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 06/29/2016] [Accepted: 07/21/2016] [Indexed: 01/03/2023] Open
Abstract
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+ transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+ transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.
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Affiliation(s)
- Reza Ashrafi
- Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK
- *Reza Ashrafi:
| | - Marianne Yon
- Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK
| | - Lucy Pickavance
- Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK
| | - Joseph Yanni Gerges
- Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK
| | - Gershan Davis
- Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK
| | - John Wilding
- Department of Obesity & Endocrinology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, 4th Floor, UCD, Duncan Building, Daulby Street, Liverpool L69 3GA, UK
| | - Kun Jian
- Biological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UK
| | - Henggui Zhang
- Biological Physics Group, School of Physics & Astronomy, University of Manchester, Schuster Building, Oxford Road, Manchester M13 9PL, UK
| | - George Hart
- Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK
| | - Mark Boyett
- Institute of Cardiovascular Sciences, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK
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Boukhris M, Elhadj ZI, Terra AW, Tomasello SD, Galassi AR, Boukhris B. Reply to “Effect of cardiac rehabilitation on ventricular repolarization in patients with type 2 diabetes and coronary heart disease: Non-invasive quantification via transmural dispersion of repolarization”. Heart Lung 2015; 44:461. [DOI: 10.1016/j.hrtlng.2015.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Castro-Torres Y, Carmona-Puerta R, Katholi RE. Ventricular repolarization markers for predicting malignant arrhythmias in clinical practice. World J Clin Cases 2015; 3:705-720. [PMID: 26301231 PMCID: PMC4539410 DOI: 10.12998/wjcc.v3.i8.705] [Citation(s) in RCA: 92] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 02/22/2015] [Accepted: 06/08/2015] [Indexed: 02/05/2023] Open
Abstract
Malignant cardiac arrhythmias which result in sudden cardiac death may be present in individuals apparently healthy or be associated with other medical conditions. The way to predict their appearance represents a challenge for the medical community due to the tragic outcomes in most cases. In the last two decades some ventricular repolarization (VR) markers have been found to be useful to predict malignant cardiac arrhythmias in several clinical conditions. The corrected QT, QT dispersion, Tpeak-Tend, Tpeak-Tend dispersion and Tp-e/QT have been studied and implemented in clinical practice for this purpose. These markers are obtained from 12 lead surface electrocardiogram. In this review we discuss how these markers have demonstrated to be effective to predict malignant arrhythmias in medical conditions such as long and short QT syndromes, Brugada syndrome, early repolarization syndrome, acute myocardial ischemia, heart failure, hypertension, diabetes mellitus, obesity and highly trained athletes. Also the main pathophysiological mechanisms that explain the arrhythmogenic predisposition in these diseases and the basis for the VR markers are discussed. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients.
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Chang YC, Wu CC, Lin CH, Wu YW, Yang YC, Chang TJ, Jiang YD, Chuang LM. Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors. PLoS One 2015; 10:e0133192. [PMID: 26185995 PMCID: PMC4505945 DOI: 10.1371/journal.pone.0133192] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 06/23/2015] [Indexed: 11/18/2022] Open
Abstract
Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion (r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight (r = 0.15, p = 0.01), and hemoglobin A1c (r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking (p = 0.02), body weight (p = 0.04), total cholesterol levels (p = 0.05), and possibly estimated glomerular filtration rate (p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels.
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Affiliation(s)
- Yi-Cheng Chang
- Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, HsinChu branch, HsinChu, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medicine, College of Medicine, National Taiwan University, Taipei; Taiwan
| | - Chau-Chung Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Primary Care Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Hung Lin
- Department of Internal Medicine, Taipei Medical University Hospital, Taipei Taiwan
| | - Yen-Wen Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Nuclear Medicine and Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Departments of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ying-Chieh Yang
- Department of Internal Medicine, National Taiwan University Hospital, HsinChu branch, HsinChu, Taiwan
| | - Tien-Jyun Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medicine, College of Medicine, National Taiwan University, Taipei; Taiwan
| | - Yi-Der Jiang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medicine, College of Medicine, National Taiwan University, Taipei; Taiwan
| | - Lee-Ming Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medicine, College of Medicine, National Taiwan University, Taipei; Taiwan
- Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- * E-mail:
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Hu YF, Dawkins JF, Cho HC, Marbán E, Cingolani E. Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med 2015; 6:245ra94. [PMID: 25031269 DOI: 10.1126/scitranslmed.3008681] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model.
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Affiliation(s)
- Yu-Feng Hu
- Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA. Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan
| | | | - Hee Cheol Cho
- Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA
| | - Eduardo Marbán
- Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA.
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AAGAARD PHILIP, BRAUNSCHWEIG FRIEDER, WECKE LILIANE, SAHLÉN ANDERS, BERGFELDT LENNART. Early Repolarization in Middle-Age Runners. Med Sci Sports Exerc 2014; 46:1285-92. [DOI: 10.1249/mss.0000000000000251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Voulgari C, Pagoni S, Tesfaye S, Tentolouris N. The spatial QRS-T angle: implications in clinical practice. Curr Cardiol Rev 2014; 9:197-210. [PMID: 23909632 PMCID: PMC3780345 DOI: 10.2174/1573403x113099990031] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 03/19/2013] [Indexed: 12/14/2022] Open
Abstract
The ventricular gradient (VG) as a concept was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. The contemporary spatial QRS-T angle is based on the concept of the VG and defined as its mathematical and physiological integral. Its current major clinical use is to assess the cardiac primary repolarization abnormalities in 3-dimensional spatial vectorial plans which are normally untraced in the presence of secondary electrophysiological activity in a 2-dimensional routine electrocardiogram (ECG). Currently the calculation of the spatial QRS-T angle can be easily computed on the basis of a classical ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local heterogeneity of the myocardial ventricular action potention duration. Recent population-based studies suggest that the spatial QRS-T angle is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary cardiovascular prevention efforts and should be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial QRS-T angle. The main focus is its role in ECG assessment of dispersion of repolarization, a key factor in arrythmogeneity.
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Affiliation(s)
- Christina Voulgari
- First Department of Propaudeutic Internal Medicine, “Laiko” General Hospital, Athens University Medical School, Greece.
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Prognostic value of T peak-to-end interval for risk stratification after acute myocardial infarction. EGYPTIAN JOURNAL OF CRITICAL CARE MEDICINE 2014. [DOI: 10.1016/j.ejccm.2014.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major. PLoS One 2014; 9:e86524. [PMID: 24475137 PMCID: PMC3903540 DOI: 10.1371/journal.pone.0086524] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Accepted: 12/10/2013] [Indexed: 11/19/2022] Open
Abstract
Background Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. Methods and Results Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = −0.609, p<0.001), SD-QTc (r = −0.572, p<0.001), and QTc dispersion (r = −0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. Conclusions Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.
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Abstract
Late I Na is an integral part of the sodium current, which persists long after the fast-inactivating component. The magnitude of the late I Na is relatively small in all species and in all types of cardiomyocytes as compared with the amplitude of the fast sodium current, but it contributes significantly to the shape and duration of the action potential. This late component had been shown to increase in several acquired or congenital conditions, including hypoxia, oxidative stress, and heart failure, or due to mutations in SCN5A, which encodes the α-subunit of the sodium channel, as well as in channel-interacting proteins, including multiple β subunits and anchoring proteins. Patients with enhanced late I Na exhibit the type-3 long QT syndrome (LQT3) characterized by high propensity for the life-threatening ventricular arrhythmias, such as Torsade de Pointes (TdP), as well as for atrial fibrillation. There are several distinct mechanisms of arrhythmogenesis due to abnormal late I Na, including abnormal automaticity, early and delayed after depolarization-induced triggered activity, and dramatic increase of ventricular dispersion of repolarization. Many local anesthetic and antiarrhythmic agents have a higher potency to block late I Na as compared with fast I Na. Several novel compounds, including ranolazine, GS-458967, and F15845, appear to be the most selective inhibitors of cardiac late I Na reported to date. Selective inhibition of late I Na is expected to be an effective strategy for correcting these acquired and congenital channelopathies.
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Dealing with global safety issues : was the response to QT-liability of non-cardiac drugs well coordinated? Drug Saf 2013; 36:167-82. [PMID: 23417505 DOI: 10.1007/s40264-013-0016-z] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Drug-induced torsade de pointes (TdP) is a potentially fatal iatrogenic entity. Its reporting rate in association with non-cardiac drugs increased exponentially from the early 1990s and was associated with an increasing number of new non-cardiac drugs whose proarrhythmic liability was not appreciated pre-marketing. This epidemic provoked a comprehensive global response from drug regulators, drug developers and academia, which resulted in stabilization of the reporting rate of TdP. This commentary reviews the chronology and nature of, and the reasons for, this response, examines its adequacy, and proposes future strategies for dealing with such iatrogenic epidemics more effectively. It is concluded that the response was piecemeal and lacked direction. No one entity was responsible, with the result that important contributions from regulators, industry and academia lacked coordination. While the process of dealing with QT crisis seemed to have worked reasonably well in this instance, it does not seem wise to expect the next crisis in drug development to be managed as well. Future crises will need better management and the challenge is to implement a system set up to respond globally and efficiently to a perceived drug-related hazard. In this regard, we discuss the roles of new tools the legislation has provided to the regulators and the value of an integrated expert assessment of all pre-approval data that may signal a potential safety issue in the postmarketing period. We also discuss the roles of other bodies such as the WHO Collaborating Centre for International Drug Monitoring, CIOMS and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
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Shi C, Wang X, Dong F, Wang Y, Hui J, Lin Z, Yang J, Xu Y. Temporal alterations and cellular mechanisms of transmural repolarization during progression of mouse cardiac hypertrophy and failure. Acta Physiol (Oxf) 2013; 208:95-110. [PMID: 23356774 DOI: 10.1111/apha.12071] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2012] [Revised: 10/29/2012] [Accepted: 01/23/2013] [Indexed: 01/02/2023]
Abstract
AIM The remodelling of transmural dispersion of repolarization (TDR) in human heart failure (HF) and in different animal models of cardiac hypertrophy or HF remains a controversial topic. We hypothesize that TDR may exhibit temporal alterations, depending on the stage of the disease. METHODS We systematically investigated the temporal alterations of TDR during the development of cardiac hypertrophy and HF in the mouse pressure-overload model using electrophysiological and molecular biology techniques. RESULTS A progressive prolongation of QT interval and changes in the amplitude of the J wave at 2, 5, 9 and 13 weeks were found in anesthetized aorta-banded mice. Action potential duration (APD) at 90% repolarization (APD90) in subendocardial myocytes of the left ventricular free wall remained unchanged at the hypertrophic stage (2 and 5 weeks), but was significantly prolonged in HF mice at 9 and 13 weeks. However, APD90 in subepicardial myocytes exhibited a significant prolongation at 2 weeks and did not progressively extend from 2 weeks to 13 weeks in banded mice. Thus, non-parallel prolongation of APD in subendocardial and subepicardial myocytes led to a reduction in TDR at hypertrophic stage and an amplification of TDR at HF stage. Further experiments revealed that asynchronous down-regulation of voltage-dependent potassium currents (I(to,f), I(K,slow) and I(ss)) and L-type calcium currents (I(Ca-L)) in subendocardial and subepicardial myocytes may contribute to the dynamic remodelling of transmural APD. CONCLUSION The two distinct TDR modes were revealed during the progression of mouse cardiac hypertrophy and failure, indicating that the remodelling of TDR depends on the stage of the disease.
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Affiliation(s)
| | - X. Wang
- The Third Hospital of Hebei Medical University; Shijiazhuang; China
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The role of acute hyperinsulinemia in the development of cardiac arrhythmias. Naunyn Schmiedebergs Arch Pharmacol 2013; 386:435-44. [PMID: 23474828 DOI: 10.1007/s00210-013-0845-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 02/20/2013] [Indexed: 10/27/2022]
Abstract
Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.
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Zaniboni M. Heterogeneity of Intrinsic Repolarization Properties Within the Human Heart: New Insights From Simulated Three-Dimensional Current Surfaces. IEEE Trans Biomed Eng 2012; 59:2372-80. [DOI: 10.1109/tbme.2012.2204880] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- M Zaniboni
- Department of Evolutionary and Functional Biology, University of Parma, Parma, Italy.
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Hekkala AM, Swan H, Viitasalo M, Väänänen H, Toivonen L. Epinephrine bolus test in detecting long QT syndrome mutation carriers with indeterminable electrocardiographic phenotype. Ann Noninvasive Electrocardiol 2011; 16:172-9. [PMID: 21496168 DOI: 10.1111/j.1542-474x.2011.00426.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. METHODS Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T-wave peak-to-end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. RESULTS Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. CONCLUSIONS Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype-specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members.
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Affiliation(s)
- Anna-Mari Hekkala
- Helsinki University Hospital, Department of Cardiology, Helsinki, Finland.
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Collins RT. Clinical significance of prolonged QTc interval in Williams syndrome. Am J Cardiol 2011; 108:471-3. [PMID: 21550581 DOI: 10.1016/j.amjcard.2011.03.071] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2011] [Revised: 03/16/2011] [Accepted: 03/16/2011] [Indexed: 01/05/2023]
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Sun Y, Quan XQ, Fromme S, Cox RH, Zhang P, Zhang L, Guo D, Guo J, Patel C, Kowey PR, Yan GX. A novel mutation in the KCNH2 gene associated with short QT syndrome. J Mol Cell Cardiol 2011; 50:433-41. [DOI: 10.1016/j.yjmcc.2010.11.017] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2010] [Revised: 11/18/2010] [Accepted: 11/22/2010] [Indexed: 11/28/2022]
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Alsheikh-Ali AA, Madias C, Supran S, Link MS. Marked Variability in Susceptibility to Ventricular Fibrillation in an Experimental Commotio Cordis Model. Circulation 2010; 122:2499-504. [DOI: 10.1161/circulationaha.110.955336] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Alawi A. Alsheikh-Ali
- From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.)
| | - Christopher Madias
- From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.)
| | - Stacey Supran
- From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.)
| | - Mark S. Link
- From the Cardiac Arrhythmia Center, Division of Cardiology (C.M., M.S.L.), and Clinical Care Research Division (S.S.), Tufts Medical Center, Boston, Mass; and Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates (A.A.A.-A.)
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Rubulis A, Bergfeldt L, Rydén L, Jensen J. Prediction of cardiovascular death and myocardial infarction by the QRS-T angle and T vector loop morphology after angioplasty in stable angina pectoris: an 8-year follow-up. J Electrocardiol 2010; 43:310-7. [DOI: 10.1016/j.jelectrocard.2010.05.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2010] [Indexed: 11/26/2022]
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