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1
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Wang Y, Li Q, Xu G, Yang Y, He F. Association between elevated serum parathyroid hormone and QTc interval prolongation in chronic kidney disease patients. Int Urol Nephrol 2025:10.1007/s11255-025-04479-1. [PMID: 40172614 DOI: 10.1007/s11255-025-04479-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/21/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE Heart rate-corrected (QTc) interval prolongation is frequently linked to fatal arrhythmias and sudden cardiac death in chronic kidney disease (CKD) patients. In this cross-sectional study, we assessed the prevalence of prolonged QTc intervals and identified clinical factors associated with them across different stages of kidney failure. METHODS 723 patients with CKD stages 2-5 who had electrocardiogram records available were analyzed retrospectively. QTc intervals were calculated by correcting the QT intervals for all patients included in the study. QTc interval prolongation defined as a QTc interval ˃ 440 ms was assessed for its prevalence and its association with various clinical factors. RESULTS A total of 723 patients with CKD stages 2-5 were finally included in this study, among which 420 (58.1%) were male. The average age of the participants was 48.2 ± 14.6 years old. In patients with CKD stages 2-4, the prevalence of QTc interval prolongation was 26%, 24.1%, and 37.8%, respectively. Among patients with CKD stage 5, those not on dialysis had a prevalence of 63%, while those undergoing dialysis had a prevalence of 74.3%. Multivariate logistic regression analysis revealed that elevated levels of parathyroid hormone (PTH) were significantly associated with an increased risk of QTc intervals prolongation in CKD patients (aOR = 1.384, 95% CI 1.173-1.632; P < 0.001). This suggests that higher PTH levels may contribute to QTc interval prolongation in this population. The patients were then grouped by CKD stages. Elevated PTH levels were independently associated with an increased risk of QTc interval prolongation specifically in CKD stages 4 and 5 patients who were not on dialysis. After adjusting for potential confounders, this association remained significant (CKD stage 4: aOR = 2.571, 95% CI 1.030-6.416; P < 0.001; CKD stage 5, non-dialysis: aOR = 1.333, 95% CI 1.063-1.671; P < 0.001). CONCLUSION In patients with CKD, the prevalence of QTc prolongation increases with advancing CKD stages. Specially, among patients with CKD stage 4 and stage 5 who were not on dialysis, elevated PTH levels were independently associated with an increased risk of QTc interval prolongation.
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Affiliation(s)
- Yanan Wang
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Qing Li
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Gang Xu
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Yi Yang
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Fan He
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China.
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
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Schwartz PJ, Cerea P. A paradigm change in sudden cardiac death risk prediction: 'static' goes out, 'dynamic' comes in. Eur Heart J 2024; 45:820-822. [PMID: 38320251 DOI: 10.1093/eurheartj/ehae051] [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: 02/08/2024] Open
Affiliation(s)
- Peter J Schwartz
- Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Istituto Auxologico Italiano IRCCS, Via Pier Lombardo, 22, 20135 Milan, Italy
| | - Paolo Cerea
- Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Istituto Auxologico Italiano IRCCS, Via Pier Lombardo, 22, 20135 Milan, Italy
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3
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Pham HN, Holmstrom L, Chugh H, Uy-Evanado A, Nakamura K, Zhang Z, Salvucci A, Jui J, Reinier K, Chugh SS. Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death. Eur Heart J 2024; 45:809-819. [PMID: 37956651 PMCID: PMC10919917 DOI: 10.1093/eurheartj/ehad770] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 10/23/2023] [Accepted: 11/06/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND AND AIMS Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. METHODS The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015-17) and 203 validation cases (2015-21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. RESULTS Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); P < .001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); P < .001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727-0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837-0.902)] and California cohorts. CONCLUSIONS Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.
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Affiliation(s)
- Hoang Nhat Pham
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Lauri Holmstrom
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Harpriya Chugh
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Audrey Uy-Evanado
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Kotoka Nakamura
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Zijun Zhang
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | | | - Jonathan Jui
- Department of Emergency Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Kyndaron Reinier
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
| | - Sumeet S Chugh
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, Advanced Health Sciences Pavilion, Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, USA
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4
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Qiu Y, Jiang P, Huang Y. Anthracycline-induced cardiotoxicity: mechanisms, monitoring, and prevention. Front Cardiovasc Med 2023; 10:1242596. [PMID: 38173817 PMCID: PMC10762801 DOI: 10.3389/fcvm.2023.1242596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024] Open
Abstract
Anthracyclines are the most fundamental and important treatment of several cancers especially for lymphoma and breast cancer. However, their use is limited by a dose-dependent cardiotoxicity which may emerge early at the initiation of anthracycline administration or several years after termination of the therapy. A full comprehending of the mechanisms of anthracycline-induced cardiotoxicity, which has not been achieved and is currently under the efforts, is critical to the advance of developing effective methods to protect against the cardiotoxicity, as well as to early detect and treat it. Therefore, we review the recent progress of the mechanism underlying anthracycline-induced cardiotoxicity, as well as approaches to monitor and prevent this issue.
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Affiliation(s)
- Yun Qiu
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Piao Jiang
- Department of Oncology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- The First Clinical Medical College, Nanchang University, Nanchang, China
| | - Yingmei Huang
- Department of Cardiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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Fotbolcu H, Soysal P. Effect of insomnia and excessive daytime sleepiness on cardiac functions in older adults. Psychogeriatrics 2023; 23:800-807. [PMID: 37414531 DOI: 10.1111/psyg.12999] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/08/2023] [Accepted: 06/12/2023] [Indexed: 07/08/2023]
Abstract
BACKGROUND We investigated the potential harmful effect in older adults of insomnia and excessive daytime sleepiness (EDS) on myocardial functions and electrophysiologic changes of the heart in terms of heart rate and QT intervals corrected for heart rate (QTc). METHODS The study included 32 insomnia patients and 30 control subjects. An Insomnia Severity Index score of ≥15 indicated insomnia, while a score of <8 was accepted as the control group. The Epworth Sleepiness Scale was used to assess EDS, with a score of ≥11/24 points indicating EDS. Diastolic and systolic functions were evaluated in each patient by transthoracic two-dimensional, conventional and tissue Doppler echocardiography. Heart rate and QTc were calculated for electrophysiologic changes. RESULTS The mean age was 73.2 ± 7.9 years, with 59.7% being female. Biventricular systolic and diastolic functions were impaired in the insomnia patients. The E' value for diastolic function was lower in the patients with insomnia than the controls (5.99 ± 1.59 vs. 6.88 ± 0.97, P = 0.053). Furthermore, values for the systolic function parameters Lateral-S (7.41 ± 1.92 vs. 9.37 ± 1.83, P < 0.001), Septal-S (6.69 ± 1.40 vs. 8.10 ± 1.30, P = 0.001), and Tricuspid-S (12.25 ± 2.00 vs. 14.37 ± 3.13, P = 0.004) were lower for insomnia patients than for controls. In the case of EDS coexistence, the heart rate and QTc values were higher than the controls (76.47 ± 7.18 vs. 71.03 ± 10.95, P = 0.001, and 413.72 ± 28.24 vs. 394.67 ± 24.47, P = 0.015, respectively). CONCLUSION Insomnia is associated with impaired systolic-diastolic functions, independent of EDS. The co-existence of insomnia and EDS may lead to electrophysiological changes in older adults, including increased heart rate and longer QTc.
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Affiliation(s)
- Hakan Fotbolcu
- Department of Cardiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Pinar Soysal
- Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
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6
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Mia S, Sonkar R, Williams L, Latimer MN, Rawnsley DR, Rana S, He J, Dierickx P, Kim T, Xie M, Habegger KM, Kubo M, Zhou L, Thomsen MB, Prabhu SD, Frank SJ, Brookes PS, Lazar MA, Diwan A, Young ME. Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology. JACC Basic Transl Sci 2023; 8:1141-1156. [PMID: 37791313 PMCID: PMC10543917 DOI: 10.1016/j.jacbts.2023.03.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 03/06/2023] [Accepted: 03/07/2023] [Indexed: 10/05/2023]
Abstract
Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology.
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Affiliation(s)
- Sobuj Mia
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Ravi Sonkar
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Lamario Williams
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mary N. Latimer
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - David R. Rawnsley
- Departments of Medicine, Cell Biology and Physiology, Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Samir Rana
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jin He
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Pieterjan Dierickx
- Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
| | - Teayoun Kim
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Min Xie
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Kirk M. Habegger
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Masato Kubo
- Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan
- Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), RIKEN Yokohama Institute, Kanagawa, Japan
| | - Lufang Zhou
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Morten B. Thomsen
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Demark
| | - Sumanth D. Prabhu
- Departments of Medicine, Cell Biology and Physiology, Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Stuart J. Frank
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Endocrinology Section, Birmingham VAMC Medical Service, Birmingham, Alabama, USA
| | - Paul S. Brookes
- Department of Anesthesiology and Perioperative Medicine, University of Rochester, Rochester, New York, USA
| | - Mitchell A. Lazar
- Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Abhinav Diwan
- Departments of Medicine, Cell Biology and Physiology, Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA
- John Cochran VA Medical Center, St. Louis, Missouri, USA
| | - Martin E. Young
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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7
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Neumann B, Vink AS, Hermans BJM, Lieve KVV, Cömert D, Beckmann BM, Clur SAB, Blom NA, Delhaas T, Wilde AAM, Kääb S, Postema PG, Sinner MF. Manual vs. automatic assessment of the QT-interval and corrected QT. Europace 2023; 25:euad213. [PMID: 37470430 PMCID: PMC10469369 DOI: 10.1093/europace/euad213] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/29/2023] [Accepted: 06/29/2023] [Indexed: 07/21/2023] Open
Abstract
AIMS Sudden cardiac death (SCD) is challenging to predict. Electrocardiogram (ECG)-derived heart rate-corrected QT-interval (QTc) is used for SCD-risk assessment. QTc is preferably determined manually, but vendor-provided automatic results from ECG recorders are convenient. Agreement between manual and automatic assessments is unclear for populations with aberrant QTc. We aimed to systematically assess pairwise agreement of automatic and manual QT-intervals and QTc. METHODS AND RESULTS A multi-centre cohort enriching aberrant QTc comprised ECGs of healthy controls and long-QT syndrome (LQTS) patients. Manual QT-intervals and QTc were determined by the tangent and threshold methods and compared to automatically generated, vendor-provided values. We assessed agreement globally by intra-class correlation coefficients and pairwise by Bland-Altman analyses and 95% limits of agreement (LoA). Further, manual results were compared to a novel automatic QT-interval algorithm. ECGs of 1263 participants (720 LQTS patients; 543 controls) were available [median age 34 (inter-quartile range 35) years, 55% women]. Comparing cohort means, automatic and manual QT-intervals and QTc were similar. However, pairwise Bland-Altman-based agreement was highly discrepant. For QT-interval, LoAs spanned 95 (tangent) and 92 ms (threshold), respectively. For QTc, the spread was 108 and 105 ms, respectively. LQTS patients exhibited more pronounced differences. For automatic QTc results from 440-540 ms (tangent) and 430-530 ms (threshold), misassessment risk was highest. Novel automatic QT-interval algorithms may narrow this range. CONCLUSION Pairwise vendor-provided automatic and manual QT-interval and QTc results can be highly discrepant. Novel automatic algorithms may improve agreement. Within the above ranges, automatic QT-interval and QTc results require manual confirmation, particularly if T-wave morphology is challenging.
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Affiliation(s)
- Benjamin Neumann
- Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, Germany
| | - A Suzanne Vink
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
- Department of Pediatric Cardiology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ben J M Hermans
- Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - Krystien V V Lieve
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
| | - Didem Cömert
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
| | - Britt-Maria Beckmann
- Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany
- Department of Legal Medicine, Goethe Univeristy, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Sally-Ann B Clur
- Department of Pediatric Cardiology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nico A Blom
- Department of Pediatric Cardiology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Tammo Delhaas
- Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - Arthur A M Wilde
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
- Department of Pediatric Cardiology, Leiden University Medical Center, Leiden, The Netherlands
- Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Stefan Kääb
- Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, Germany
| | - Pieter G Postema
- Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands
| | - Moritz F Sinner
- Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, Germany
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8
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Boshen Y, Yuankang Z, Xinjie Z, Taixi L, Kaifan N, Zhixiang W, Juan S, Junli D, Suiji L, Xia L, Chengxing S. Triglyceride-glucose index is associated with the occurrence and prognosis of cardiac arrest: a multicenter retrospective observational study. Cardiovasc Diabetol 2023; 22:190. [PMID: 37501144 PMCID: PMC10375765 DOI: 10.1186/s12933-023-01918-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 07/06/2023] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND Triglyceride-glucose (TyG) index is an efficient indicator of insulin resistance and is proven to be a valuable marker in several cardiovascular diseases. However, the relationship between TyG index and cardiac arrest (CA) remains unclear. The present study aimed to investigate the association of the TyG index with the occurrence and clinical outcomes of CA. METHODS In this retrospective, multicenter, observational study, critically ill patients, including patients post-CA, were identified from the eICU Collaborative Research Database and evaluated. The TyG index for each patient was calculated using values of triglycerides and glucose recorded within 24 h of intensive care unit (ICU) admission. In-hospital mortality and ICU mortality were the primary clinical outcomes. Logistic regression, restricted cubic spline (RCS), and correlation analyses were performed to explore the relationship between the TyG index and clinical outcomes. Propensity score matching (PSM), overlap weighting (OW), and inverse probability of treatment weighting (IPTW) were adopted to balance the baseline characteristics of patients and minimize selection bias to confirm the robustness of the results. Subgroup analysis based on different modifiers was also performed. RESULTS Overall, 24,689 critically ill patients, including 1021 patients post-CA, were enrolled. The TyG index was significantly higher in patients post-CA than in those without CA (9.20 (8.72-9.69) vs. 8.89 (8.45-9.41)), and the TyG index had a moderate discrimination ability to identify patients with CA from the overall population (area under the curve = 0.625). Multivariate logistic regression indicated that the TyG index was an independent risk factor for in-hospital mortality (OR = 1.28, 95% CI: 1.03-1.58) and ICU mortality (OR = 1.27, 95% CI: 1.02-1.58) in patients post-CA. RCS curves revealed that an increased TyG index was linearly related to higher risks of in-hospital and ICU mortality (P for nonlinear: 0.225 and 0.271, respectively). Even after adjusting by PSM, IPTW, and OW, the TyG index remained a risk factor for in-hospital mortality and ICU mortality in patients experiencing CA, which was independent of age, BMI, sex, etc. Correlation analyses revealed that TyG index was negatively correlated with the neurological status of patients post-CA. CONCLUSION Elevated TyG index is significantly associated with the occurrence of CA and higher mortality risk in patients post-CA. Our findings extend the landscape of TyG index in cardiovascular diseases, which requires further prospective cohort study.
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Affiliation(s)
- Yang Boshen
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhu Yuankang
- Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Gerontology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng Xinjie
- Department of Respiratory Medicine, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu, China
| | - Li Taixi
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Niu Kaifan
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wang Zhixiang
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Song Juan
- Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China
| | - Duan Junli
- Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Gerontology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Suiji
- Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.
| | - Lu Xia
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Shen Chengxing
- Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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9
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Ali AM, Radtke KK, Hesseling AC, Winckler J, Schaaf HS, Draper HR, Solans BP, van der Laan L, Hughes J, Fourie B, Nielsen J, Garcia-Prats AJ, Savic RM. QT Interval Prolongation with One or More QT-Prolonging Agents Used as Part of a Multidrug Regimen for Rifampicin-Resistant Tuberculosis Treatment: Findings from Two Pediatric Studies. Antimicrob Agents Chemother 2023; 67:e0144822. [PMID: 37358463 PMCID: PMC10353402 DOI: 10.1128/aac.01448-22] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 05/22/2023] [Indexed: 06/27/2023] Open
Abstract
Rifampicin-resistant tuberculosis (RR-TB) involves treatment with many drugs that can prolong the QT interval; this risk may increase when multiple QT-prolonging drugs are used together. We assessed QT interval prolongation in children with RR-TB receiving one or more QT-prolonging drugs. Data were obtained from two prospective observational studies in Cape Town, South Africa. Electrocardiograms were performed before and after drug administration of clofazimine (CFZ), levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), and delamanid. The change in Fridericia-corrected QT (QTcF) was modeled. Drug and other covariate effects were quantified. A total of 88 children with a median (2.5th-to-97.5th range) age of 3.9 (0.5 to 15.7) years were included, of whom 55 (62.5%) were under 5 years of age. A QTcF interval of >450 ms was observed in 7 patient-visits: regimens were CFZ+MFX (n = 3), CFZ+BDQ+LFX (n = 2), CFZ alone (n = 1), and MFX alone (n = 1). There were no events with a QTcF interval of >500 ms. In a multivariate analysis, CFZ+MFX was associated with a 13.0-ms increase in change in QTcF (P < 0.001) and in maximum QTcF (P = 0.0166) compared to those when other MFX- or LFX-based regimens were used. In conclusion, we found a low risk of QTcF interval prolongation in children with RR-TB who received at least one QT-prolonging drug. Greater increases in maximum QTcF and ΔQTcF were observed when MFX and CFZ were used together. Future studies characterizing exposure-QTcF responses in children will be helpful to ensure safety with higher doses if required for effective treatment of RR-TB.
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Affiliation(s)
- Ali Mohamed Ali
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA
- Bagamoyo Research and Training Center, Ifakara Health Institute, Bagamoyo, Tanzania
| | - Kendra K. Radtke
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA
| | - Anneke C. Hesseling
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Jana Winckler
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - H. Simon Schaaf
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Heather R. Draper
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Belén P. Solans
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA
| | - Louvina van der Laan
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Jennifer Hughes
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Barend Fourie
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - James Nielsen
- Department of Pediatrics, New York University School of Medicine, New York, New York, USA
| | - Anthony J. Garcia-Prats
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
- Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Rada M. Savic
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA
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Muylle KM, van Laere S, Pannone L, Coenen S, de Asmundis C, Dupont AG, Cornu P. Added value of patient- and drug-related factors to stratify drug-drug interaction alerts for risk of QT prolongation: Development and validation of a risk prediction model. Br J Clin Pharmacol 2023; 89:1374-1385. [PMID: 36321834 DOI: 10.1111/bcp.15580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 09/14/2022] [Accepted: 10/30/2022] [Indexed: 11/24/2022] Open
Abstract
AIMS Many clinical decision support systems trigger warning alerts for drug-drug interactions potentially leading to QT prolongation and torsades de pointes (QT-DDIs). Unfortunately, there is overalerting and underalerting because stratification is only based on a fixed QT-DDI severity level. We aimed to improve QT-DDI alerting by developing and validating a risk prediction model considering patient- and drug-related factors. METHODS We fitted 31 predictor candidates to a stepwise linear regression for 1000 bootstrap samples and selected the predictors present in 95% of the 1000 models. A final linear regression model with those variables was fitted on the original development sample (350 QT-DDIs). This model was validated on an external dataset (143 QT-DDIs). Both true QTc and predicted QTc were stratified into three risk levels (low, moderate and high). Stratification of QT-DDIs could be appropriate (predicted risk = true risk), acceptable (one risk level difference) or inappropriate (two risk levels difference). RESULTS The final model included 11 predictors with the three most important being use of antiarrhythmics, age and baseline QTc. Comparing current practice to the prediction model, appropriate stratification increased significantly from 37% to 54% appropriate QT-DDIs (increase of 17.5% on average [95% CI +5.4% to +29.6%], padj = 0.006) and inappropriate stratification decreased significantly from 13% to 1% inappropriate QT-DDIs (decrease of 11.2% on average [95% CI -17.7% to -4.7%], padj ≤ 0.001). CONCLUSION The prediction model including patient- and drug-related factors outperformed QT alerting based on QT-DDI severity alone and therefore is a promising strategy to improve DDI alerting.
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Affiliation(s)
- Katoo M Muylle
- Department of Pharmaceutical and Pharmacological Sciences, Research Group Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Sven van Laere
- Department of Public Health, Research Group of Biostatistics and Medical Informatics, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Luigi Pannone
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, European Reference Networks Guard-Heart, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels, 1090, Belgium
| | - Samuel Coenen
- Department of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, Campus Drie Eiken, Gouverneur Kinsbergencentrum, University of Antwerp, Doornstraat 331, Antwerp, 2610, Belgium
| | - Carlo de Asmundis
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, European Reference Networks Guard-Heart, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels, 1090, Belgium
| | - Alain G Dupont
- Department of Pharmaceutical and Pharmacological Sciences, Research Group Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Pieter Cornu
- Department of Pharmaceutical and Pharmacological Sciences, Research Group Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.,Department of Medical Informatics, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels, 1090, Belgium
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11
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Kim HJ, Jung D, Sunwoo SH, Jung S, Koo JH, Kim DH. Integration of Conductive Nanocomposites and Nanomembranes for High‐Performance Stretchable Conductors. ADVANCED NANOBIOMED RESEARCH 2023. [DOI: 10.1002/anbr.202200153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023] Open
Affiliation(s)
- Hye Jin Kim
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes Seoul National University Seoul 08826 Republic of Korea
| | - Dongjun Jung
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes Seoul National University Seoul 08826 Republic of Korea
| | - Sung-Hyuk Sunwoo
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- Institute of Radiation Medicine Seoul National University Medical Research Center Seoul 03080 Republic of Korea
| | - Sonwoo Jung
- School of Chemical and Biological Engineering, and Institute of Chemical Processes Seoul National University Seoul 08826 Republic of Korea
| | - Ja Hoon Koo
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes Seoul National University Seoul 08826 Republic of Korea
| | - Dae-Hyeong Kim
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes Seoul National University Seoul 08826 Republic of Korea
- Department of Materials Science and Engineering Seoul National University Seoul 08826 Republic of Korea
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12
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Lin N, Zhang H, Li X, Niu Y, Gu H, Lu S, Yang Z, Su Q, Qin L. The influence of different glucose tolerance on QTc interval: a population-based study. BMC Cardiovasc Disord 2023; 23:47. [PMID: 36698056 PMCID: PMC9875502 DOI: 10.1186/s12872-023-03081-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 01/19/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Corrected QT (QTc) interval has been reported to be associated with type 2 diabetes. This study aimed to explore the relationship between different glucose tolerance and QTc intervals among middle-aged and older Chinese individuals. METHODS We conducted a cross-sectional analysis that included 9898 subjects (3194 men and 6704 women) in a Chinese population. Glucose tolerance was studied during the oral glucose tolerance test (OGTT). Insulin, blood pressure, hemoglobin A1c (HbA1c), serum lipids, hepatic transaminases and waist-to-hip ratio were assessed. The QTc interval was derived from ECG recordings, and the subjects were stratified based on different glucose tolerance. RESULTS QTc interval levels were increased significantly in the subjects with abnormal glucose metabolism compared with the normal glucose regulation group. Multiple regression analyses showed that the QTc interval was significantly associated with fasting plasma glucose, 2-h OGTT plasma glucose and HbA1c. The odds ratio of prolonged QTc was 1.396 for impaired glucose regulation (IFG)/impaired fasting glucose (IGT) (95% CI 0.126-1.730), and 1.342 for type 2 diabetes (95% CI 0.142-1.577) after all potential confounders were adjusted. CONCLUSIONS Impaired glucose tolerance (IGR) and diabetes are associated with prolonged QTc intervals among middle-aged and older Chinese individuals. Abnormal glucose regulation can be used to monitor the QTc interval in the population.
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Affiliation(s)
- Ning Lin
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China ,grid.284723.80000 0000 8877 7471Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hongmei Zhang
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyong Li
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixin Niu
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongxia Gu
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
| | - Shuai Lu
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
| | - Zhen Yang
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Su
- grid.412987.10000 0004 0630 1330Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Qin
- grid.39436.3b0000 0001 2323 5732Department of Endocrinology, Chongming Hospital affiliated to Shanghai University of Health & Medicine Science, Shanghai, China
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13
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Mann T, Moses A, Yesaulov A, Hochstadt A, Granot Y, Rosso R, Shacham Y, Chorin E. QT interval dynamics in patients with ST-elevation MI. Front Cardiovasc Med 2023; 9:1056456. [PMID: 36684584 PMCID: PMC9853398 DOI: 10.3389/fcvm.2022.1056456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/07/2022] [Indexed: 01/08/2023] Open
Abstract
Background An association between excessively prolonged QT and ventricular arrhythmia in patients with ST-elevation myocardial infarction has been described; however, the QT dynamics, characterization, and long-term predictive value are not well known. Objective To characterize QT interval dynamics in patients undergoing ST elevation myocardial infarction (STEMI) and determine its association with mortality. Methods A retrospective analysis of 4,936 consecutive patients, hospitalized for STEMI between 01/2013-12/2021. Patients with less than three electrocardiograms (ECGs) during index hospitalization were excluded. Baseline demographics, cardiovascular history, clinical risk factors, treatment measures, laboratory results, and mortality data were retrieved from the hospital's electronic medical records. Results We included 1,054 patients and 5,021 ECGs in our cohort with a median follow-up of 6 years [interquartile range (IQR) 4.3-7.4 years]. The QT was longer in women in comparison to men (428.6 ms ± 33.4 versus 419.8 ms ± 32.52, P-value = 0.001). QT prolongation was greater in females, elderly patients, and patients with STEMI caused by occlusion of the left anterior descending (LAD) coronary artery. We determined QT cutoff to be 445 ms. This value of QT divided our cohort upon arrival into a long QT group (217 patients, 26% of the cohort) and a "normal" QT group (835 patients, 74% of the cohort). The long QT group experienced an increase in combined short and long terms all-cause mortality. The QT upon arrival, on day 2 of hospitalization, and before discharge from the hospital, correlated with long-term mortality. Conclusion QT duration is often prolonged during STEMI; this prolongation is associated with increased mortality and adverse events. Gender is an important mediator of QT dynamics.
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Vila BDCP, Vanhoni MS, Sousa MG. QT interval instability and variability in dogs with naturally-occurring hypercortisolism. Vet Res Commun 2023; 47:121-130. [PMID: 35575953 DOI: 10.1007/s11259-022-09936-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/04/2022] [Indexed: 01/27/2023]
Abstract
Hypercortisolism is one of the most common endocrine diseases in dogs. In humans, it is clearly associated with a higher risk of cardiovascular events, but studies in dogs are scarce. To investigate the arrhythmogenic risk of dogs with naturally-occurring hypercortisolism (NOHC), indices of variability and instability of the QT interval were retrospectively studied in 38 dogs with NOHC and prospectively studied in 12 healthy dogs: variance (QTv), total instability (TI), short-term (STI) and long-term (LTI), and mean (QTm). Except for QTm, all parameters studied were higher in the NOHC group than in the control group. In addition, STI and QTv showed moderate positive correlation with left ventricle wall thickness. The NOHC group was subdivided according to cortisol suppression pattern in the low-dose dexamethasone suppression test. All electrocardiographic indices of partial and absent suppression patterns were numerically higher than healthy dogs. QTv and TI were lower in the control group than in both NOHC subgroups. LTI and STI were lower in the CG than in the group with the partial suppression pattern. There was no statistical difference between sex groups in any of the electrocardiographic parameters studied. This result might indicate that the etiology of NOHC, and its consequent influence on hypothalamus-pituitary-adrenal axis could interfere on the heterogeneity of ventricular repolarization parameters in different ways, especially in the short-term and the long-term stability; however further studies are necessary to understand the role of cortisol on electrical instability in dogs.
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Affiliation(s)
- Beatriz de Carvalho Pato Vila
- Laboratory of Comparative Cardiology, Department of Veterinary Medicine, Federal University of Paraná (UFPR), Rua dos Funcionários, 1540, Curitiba, PR, 80035-050, Brazil.
| | - Marcela Sigolo Vanhoni
- Laboratory of Comparative Cardiology, Department of Veterinary Medicine, Federal University of Paraná (UFPR), Rua dos Funcionários, 1540, Curitiba, PR, 80035-050, Brazil
| | - Marlos Gonçalves Sousa
- Laboratory of Comparative Cardiology, Department of Veterinary Medicine, Federal University of Paraná (UFPR), Rua dos Funcionários, 1540, Curitiba, PR, 80035-050, Brazil
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Moderately Prolonged QTc in Computer-Assessed ECG, Random Variation or Significant Risk Factor? A Literature Review. CARDIOGENETICS 2022. [DOI: 10.3390/cardiogenetics12030025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Most ECGs in European hospitals are recorded with equipment giving computer measured intervals and interpretation of the recording. In addition to measurements of interval and QRS axis, this interpretation frequently provides the Bazett’s-corrected QTc time. The introduction of computer-corrected QTc revealed QTc prolongation to be a frequent condition among medical patients. Nevertheless, the finding is frequently overlooked by the treating physician. The authors combine experience from a local hospital with a review of the current literature in this field in order to elucidate the importance of this risk factor both as congenital long QT syndrome and as acquired QT prolongation.
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16
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Lawin D, Poudel MR, Lawrenz T, Stellbrink C. Case report of a patient with congenital long QT syndrome Type 2 presenting with electrical storm: do not judge a book by its cover! Eur Heart J Case Rep 2022; 6:ytac369. [PMID: 36212623 PMCID: PMC9536292 DOI: 10.1093/ehjcr/ytac369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/28/2022] [Accepted: 09/01/2022] [Indexed: 11/21/2022]
Abstract
Background Patients with congenital long QT syndrome (LQTS) are at high risk for sudden cardiac death (SCD). Although several triggers can provoke ventricular fibrillation (VF) in patients suffering from LQTS acquired heart disease in addition to LQTS should not be overlooked. Case summary We present a case of a 47-year-old female patient who was diagnosed with congenital LQTS Type 2 at the age of 23 after surviving SCD. At that time, she underwent implantable cardioverter-defibrillator (ICD) implantation and was free of events for 24 years. Recently, the patient was referred to our institution after suffering from an ICD shock during sleep. Upon arrival she developed electrical storm and received overall six ICD shocks. The initial electrocardiogram (ECG) showed atrially triggered ventricular pacing. However, distinct ST segment elevations in the inferior leads could be observed. Thus, coronary angiography was immediately performed and showed subtotal occlusion of the right coronary artery, which was treated by drug-eluting stent implantation. Atrioventricular conduction immediately resumed after revascularization and the following non-paced ECG revealed a prolonged QT interval. Laboratory measurements confirmed acute myocardial infarction with elevated cardiac enzymes. The patient was put on betablockers, dual antiplatelet therapy, and statins and discharged in good condition. Discussion This case report highlights that diagnostic work-up in patients with LQTS presenting with VF should always include the search for additional acquired heart disease such as myocardial infarction, as a potential trigger for electrical storm. Moreover, signs of ischaemia can be discerned even in a paced ECG which should lead to immediate cardiac catheterization.
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Affiliation(s)
- Dennis Lawin
- Department of Cardiology and Intensive Care Medicine, University Hospital OWL of Bielefeld University, Campus Klinikum Bielefeld, Teutoburger Straße 50, 33604 Bielefeld, Germany
| | - Madan Raj Poudel
- Department of Cardiology and Intensive Care Medicine, University Hospital OWL of Bielefeld University, Campus Klinikum Bielefeld, Teutoburger Straße 50, 33604 Bielefeld, Germany
| | - Thorsten Lawrenz
- Department of Cardiology and Intensive Care Medicine, University Hospital OWL of Bielefeld University, Campus Klinikum Bielefeld, Teutoburger Straße 50, 33604 Bielefeld, Germany
- Faculty of Health, University Witten/Herdecke, Alfred Herrenhausen Straße 50, 58455 Witten, Germany
| | - Christoph Stellbrink
- Department of Cardiology and Intensive Care Medicine, University Hospital OWL of Bielefeld University, Campus Klinikum Bielefeld, Teutoburger Straße 50, 33604 Bielefeld, Germany
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Xue H, Li Y, Zhao Z, Ren J, Yu W, Wang F, Li X, Li J, Xia Q, Zhang Y, Li B. Deacetylation mechanism and potential reversal strategy of long QT syndrome on hERG K + channel under hypoxia. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166487. [PMID: 35840042 DOI: 10.1016/j.bbadis.2022.166487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 11/30/2022]
Abstract
Clinically, hypoxia is a major risk factor for long QT syndrome (LQTS), which is associated with many diseases, such as myocardial ischemia. LQTS can be caused by the deficiency of hERG, a potassium ion channel that plays a key role in cardiac repolarization. Modifications such as acetylation of histones or non-histone proteins can affect the protein expression. In the present study, we explored the mechanism underlying hypoxia-induced LQTS and a potential reversal strategy. Experiments were performed under hypoxia to determine transcriptional and post-transcriptional expression changes. We used real-time PCR, chromatin immunoprecipitation assay, and western blotting to determine the histones acetylation in the hERG gene and the mechanism. Molecular docking, western blotting, IP, and patch -clamp assay were performed to determine the acetylation and ubiquitination levels of hERG protein and the mechanism. hERG mRNA and protein expression were found to decrease under hypoxia. The histone deacetylation level increased under hypoxia at both H3K27 and H4 of the hERG gene. HDAC1 and HDAC2 are the key enzymes for the mechanism. HDAC6 directly interacts with hERG. The acetylation level of hERG decreased and the ubiquitination level of hERG increased under hypoxia. The inhibitors of HDAC1, HDAC2, and HDAC6 could reverse the reduction of hERG mRNA and hERG protein expression under hypoxia. In conclusion, deacetylation of hERG gene-associated histones and hERG protein might be the mechanisms for LQTS in patients with hypoxia, and the inhibition of HDAC1, HDAC2, and HDAC6 might be a promising reversal strategy for reducing hERG expression under different pathological conditions.
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Affiliation(s)
- Hui Xue
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Yuexin Li
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Zhengrong Zhao
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Jiacheng Ren
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Wenting Yu
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Fang Wang
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Xianghua Li
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Jiaxin Li
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Qianqian Xia
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Yuxin Zhang
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China
| | - Baoxin Li
- Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China.
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Isaksen JL, Ghouse J, Skov MW, Olesen MS, Holst AG, Pietersen A, Nielsen JB, Maier A, Graff C, Frikke-Schmidt R, Kanters JK. Associations between primary care electrocardiography and non-Alzheimer dementia. J Stroke Cerebrovasc Dis 2022; 31:106640. [PMID: 35830834 DOI: 10.1016/j.jstrokecerebrovasdis.2022.106640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/22/2022] [Accepted: 07/02/2022] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVES To determine whether electrocardiogram (ECG) markers are associated with incident non-Alzheimer's dementia (non-AD) and whether these markers also improve risk prediction for non-AD. MATERIALS AND METHODS We retrospectively included 170,605 primary care patients aged 60 years or older referred for an ECG by their general practitioner and followed them for a median of 7.6 years. Using Cox regression, we reported hazard ratios (HRs) for electrocardiogram markers. Subsequently, we evaluated if addition of these electrocardiogram markers to a clinical model improved risk prediction for non-AD using change in area under the receiver-operator characteristics curve (AUC). RESULTS The 5-year cumulative incidence of non-AD was 3.4 %. Increased heart rate (HR=1.06 pr. 10 bpm [95% confidence interval: 1.04-1.08], p<0.001), shorter QRS duration (HR=1.07 pr. 10 ms [1.05-1.09], p<0.001), elevated J-amplitude (HR=1.16 pr. mm [1.08-1.24], p<0.001), decreased T-peak amplitude (HR=1.02 pr. mm [1.01-1.04], p=0.002), and increased QTc (HR=1.08 pr. 20 ms [1.05-1.10], p<0.001) were associated with an increased rate of non-AD. Atrial fibrillation on the ECG (HR=1.18 [1.08-1.28], p<0.001) Sokolow-Lyon index > 35 mm (HR=1.31 [1.18-1.46], p<0.001) and borderline (HR=1.18 [1.11-1.26], p<0.001) or abnormal (HR=1.40 [1.27-1.55], p<0.001) QRS-T angle were also associated with an increased rate of non-AD. Upon addition of ECG markers to the Cox model, 5-year and 10-year C-statistic (AUC) improved significantly (delta-AUC, 0.36 [0.18-0.50] and 0.20 [0.03-0.35] %-points, respectively). CONCLUSIONS ECG markers typical of an elevated cardiovascular risk profile were associated with non-AD and improved both 5-year and 10-year risk predictions for non-AD.
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Affiliation(s)
- Jonas L Isaksen
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Jonas Ghouse
- Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - Morten W Skov
- Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - Morten S Olesen
- Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - Anders G Holst
- Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - Adrian Pietersen
- Copenhagen General Practitioners' Laboratory, Copenhagen, Denmark
| | - Jonas B Nielsen
- Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, University Hospital of Copenhagen, Rigshospitalet, Denmark; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
| | - Anja Maier
- Department of Technology, Management and Economics, Technical University of Denmark, Kgs. Lyngby, Denmark; Department of Design, Manufacturing and Engineering Management, University of Strathclyde, Glasgow, United Kingdom
| | - Claus Graff
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Ruth Frikke-Schmidt
- Department of Clinical Biochemistry, Rigshospitalet, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Jørgen K Kanters
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
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19
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Huang W, Xu R, Zhou B, Lin C, Guo Y, Xu H, Guo X. Clinical Manifestations, Monitoring, and Prognosis: A Review of Cardiotoxicity After Antitumor Strategy. Front Cardiovasc Med 2022; 9:912329. [PMID: 35757327 PMCID: PMC9226336 DOI: 10.3389/fcvm.2022.912329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/23/2022] [Indexed: 12/24/2022] Open
Abstract
The development of various antitumor drugs has significantly improved the survival of patients with cancer. Many first-line chemotherapy drugs are cytotoxic and the cardiotoxicity is one of the most significant effects that could leads to poor prognosis and decreased survival rate. Cancer treatment include traditional anthracycline drugs, as well as some new targeted drugs such as trastuzumab and ICIs. These drugs may directly or indirectly cause cardiovascular injury through different mechanisms, and lead to increasing the risk of cardiovascular disease or accelerating the development of cardiovascular disease. Cardiotoxicity is clinically manifested by arrhythmia, decreased cardiac function, or even sudden death. The cardiotoxicity caused by traditional chemotherapy drugs such as anthracyclines are significantly known. The cardiotoxicity of some new antitumor drugs such like immune checkpoint inhibitors (ICIs) is also relatively clear and requiring further observation and verification. This review is focused on major three drugs with relatively high incidence of cardiotoxicity and poor prognosis and intended to provide an update on the clinical complications and outcomes of these drugs, and we innovatively summarize the monitoring status of survivors using these drugs and discuss the biomarkers and non-invasive imaging features to identify early cardiotoxicity. Finally, we summarize the prevention that decreasing antitumor drugs-induced cardiotoxicity.
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Affiliation(s)
- Wei Huang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Rong Xu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Bin Zhou
- Laboratory of Molecular Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Center for Translational Medicine, Ministry of Education, Clinical Research Center for Birth Defects of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Chao Lin
- Department of Hematology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yingkun Guo
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Huayan Xu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xia Guo
- Department of Hematology, West China Second University Hospital, Sichuan University, Chengdu, China
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20
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Song JH, Yang C, Lee W, Kim H, Kim Y, Kim H. QTc interval prolongation due to spinal anesthesia in patients with and without diabetes: an observational study. BMC Anesthesiol 2022; 22:143. [PMID: 35562669 PMCID: PMC9102281 DOI: 10.1186/s12871-022-01614-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 03/10/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Spinal anesthesia and autonomic neuropathy (caused by diabetes) prolong the QTc interval. Changes in the duration of the QTc interval following subarachnoid blockade in patients with diabetes have not been evaluated. We hypothesized that after subarachnoid blockade, QTc interval prolongation would be greater in patients with diabetes than in those without. Accordingly, we compared the QTc interval, T wave peak-to-end interval (Tp-e interval), blood pressure, heart rate, and heart rate variability before and after spinal anesthesia in patients with and without diabetes. METHODS This prospective observational study (Clinical Research Information Service identifier: KCT0004897) was conducted in a tertiary university hospital and included 24 patients with diabetes mellitus (DM group) and 24 patients without it (control group) who were scheduled for spinal anesthesia. The QTc interval, Tp-e interval, heart rate variability, blood pressure, and heart rate were measured before (T1) and 1 (T2), 5 (T3), and 10 min (T4) following subarachnoid blockade. RESULTS Ten minutes following subarachnoid blockade, the QTc intervals of patients in the DM group were significantly longer than the baseline values, whereas the change in the QTc interval in the control group was not significant (p < 0.0001 vs. p = 0.06). CONCLUSION Spinal anesthesia caused a more significant prolongation of the QTc interval in patients with diabetes than in those without.
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Affiliation(s)
- Jang-Ho Song
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Chunwoo Yang
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Woojoo Lee
- Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Hongseok Kim
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Youngjun Kim
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hyunzu Kim
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea.
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21
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Charalambous C, Moon JC, Holly JMP, Chaturvedi N, Hughes AD, Captur G. Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort. Front Cardiovasc Med 2022; 9:863988. [PMID: 35528832 PMCID: PMC9072634 DOI: 10.3389/fcvm.2022.863988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/21/2022] [Indexed: 11/30/2022] Open
Abstract
Background As people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown. Objectives To examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort. Methods Participants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60-64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60-64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60-64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation. Results One thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60-64y with QTc prolongation [respectively: β -0.30 ms/nmol/L, (95% confidence intervals -0.44, -0.17), p < 0.001; β-28.9 ms/unit (-41.93, -15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β -0.04 ms/nmol/L (-0.08, -0.008), p = 0.019; β -2.44 ms/unit (-4.17, -0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60-64y [β -0.21 ms/nmol/L (-0.39, -0.04), p = 0.017; β -20.14 ms/unit (-36.28, -3.99), p = 0.015], steeper decline in ΔIGF-I [β -0.05 ms/nmol/L/10 years (-0.10, -0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β -2.16 ms/unit/10 years (-4.23, -0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β -5.70 ms/mmol/L (-10.23, -1.18) p = 0.014]. Conclusion Over a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted.
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Affiliation(s)
- Christos Charalambous
- UCL MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
| | - James C Moon
- UCL Institute of Cardiovascular Science, University College London, London, United Kingdom
- Cardiac MRI Unit, Barts Heart Centre, London, United Kingdom
| | - Jeff M P Holly
- National Institute for Health Research (NIHR) Bristol Nutrition Biomedical Research Unit, Level 3, University Hospitals Bristol Education and Research Centre, Bristol, United Kingdom
- Faculty of Health Sciences, School of Translational Health Sciences, Bristol Medical School, Southmead Hospital, University of Bristol, Bristol, United Kingdom
| | - Nishi Chaturvedi
- UCL MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
| | - Alun D Hughes
- UCL MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
- UCL Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Gabriella Captur
- UCL MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
- UCL Institute of Cardiovascular Science, University College London, London, United Kingdom
- Cardiology Department, Centre for Inherited Heart Muscle Conditions, The Royal Free Hospital, London, United Kingdom
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22
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QT interval extracted from 30-minute short resting Holter ECG recordings predicts mortality in heart failure. J Electrocardiol 2022; 72:109-114. [DOI: 10.1016/j.jelectrocard.2022.03.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 03/07/2022] [Accepted: 03/30/2022] [Indexed: 01/08/2023]
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Glasser J, Chin C, Samson RA, Barber BJ. A Prolonged QTc Interval Leads to the Diagnosis of Hyperthyroidism in an Adolescent Boy. J Emerg Med 2022; 62:e60-e64. [PMID: 35131131 DOI: 10.1016/j.jemermed.2021.12.007] [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: 12/01/2020] [Revised: 11/29/2021] [Accepted: 12/23/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Syncope is a common cause of pediatric emergency department visits and carries a broad differential diagnosis, which includes a few rare but critical cardiac conditions. CASE REPORT We review the case of an adolescent boy who presented to the emergency department after a syncopal event. He was found to have a prolonged QTc interval on electrocardiogram (ECG), without personal or family history or known risk factors. He was screened for thyroid dysfunction on a second ED visit for presyncope and was subsequently diagnosed with hyperthyroidism. The patient was treated with methimazole for 2 weeks and a repeat ECG showed normalization of the QTc interval with a QTc reduction of more than 100 ms; routine thyroid studies showed correction of thyroid stimulating hormone and free thyroxine levels shortly thereafter. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case and review of the medical literature should raise awareness for the emergency physician to consider evaluation of thyroid function in pediatric patients with QT interval prolongation and vice versa, potentially averting dangerous dysrhythmias.
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Affiliation(s)
- Joshua Glasser
- Department of Emergency Medicine, Penn State College of Medicine, Hershey, Pennsylvania; Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania
| | - Cindy Chin
- Department of Pediatrics, University of Arizona, Tucson, Arizona; Division of Pediatric Endocrinology, University of Arizona, Tucson, Arizona
| | - Ricardo A Samson
- Department of Pediatrics, University of Arizona, Tucson, Arizona; Division of Pediatric Cardiology, University of Arizona, Tucson, Arizona
| | - Brent J Barber
- Department of Pediatrics, University of Arizona, Tucson, Arizona; Division of Pediatric Cardiology, University of Arizona, Tucson, Arizona
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24
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Carvalho GDD, Armaganijan LV, Lopes RD, Olandoski M, Galvão BMDA, Pessoa CC, Erbano BO, Luz RSBD, Demarchi AV, Medeiros BGD, Moreira DAR. Relationship between ventricular repolarization parameters and the inducibility of ventricular arrhythmias during electrophysiological study in patients with coronary artery disease. REVISTA DA ASSOCIAÇÃO MÉDICA BRASILEIRA 2022; 68:61-66. [DOI: 10.1590/1806-9282.20210806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 10/08/2021] [Indexed: 11/21/2022]
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Ferreira G, Santander A, Chavarría L, Cardozo R, Savio F, Sobrevia L, Nicolson GL. Functional consequences of lead and mercury exposomes in the heart. Mol Aspects Med 2021; 87:101048. [PMID: 34785060 DOI: 10.1016/j.mam.2021.101048] [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: 04/14/2021] [Revised: 11/02/2021] [Accepted: 11/03/2021] [Indexed: 12/20/2022]
Abstract
Lead and mercury are heavy metals that are highly toxic to life forms. There are no known physiological processes that require them, and they do not have a particular threshold concentration to produce biologic damage. They are non-biodegradable, and they slowly accumulate in the environment in a dynamic equilibrium between air, water, soil, food, and living organisms. Their accumulation in the environment has been increasing over time, because they were not banned from use in anthropogenic industrial production. In their +2 cationic state they are powerful oxidizing agents with the ability to interfere significantly with processes that require specific divalent cations. Acute or chronic exposure to lead and mercury can produce multisystemic damage, especially in the developing nervous systems of children and fetuses, resulting in variety of neurological consequences. They can also affect the cardiovascular system and especially the heart, either directly through their action on cardiomyocytes or indirectly through their effects on innervation, humoral responses or blood vessel alterations. For example, heart function modified by these heavy metals are heart rate, contraction, excitability, and rhythm. Some cardiac molecular targets have been identified and characterized. The direct mechanisms of damage of these heavy metals on heart function are discussed. We conclude that exposome to these heavy metals, should be considered as a major relevant risk factor for cardiac diseases.
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Affiliation(s)
- Gonzalo Ferreira
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling. Department of Biophysics, Faculty of Medicine, Universidad de la República, Gral. Flores, 2125, CP 11800, Montevideo, Uruguay.
| | - Axel Santander
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling. Department of Biophysics, Faculty of Medicine, Universidad de la República, Gral. Flores, 2125, CP 11800, Montevideo, Uruguay
| | - Luisina Chavarría
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling. Department of Biophysics, Faculty of Medicine, Universidad de la República, Gral. Flores, 2125, CP 11800, Montevideo, Uruguay
| | - Romina Cardozo
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling. Department of Biophysics, Faculty of Medicine, Universidad de la República, Gral. Flores, 2125, CP 11800, Montevideo, Uruguay
| | - Florencia Savio
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling. Department of Biophysics, Faculty of Medicine, Universidad de la República, Gral. Flores, 2125, CP 11800, Montevideo, Uruguay
| | - Luis Sobrevia
- Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, Universidad Católica de Chile, Santiago, 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville, E-41012, Spain; Medical School (Faculty of Medicine), São Paulo State University (UNESP), Brazil; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Queensland, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713GZ, Groningen, the Netherlands
| | - Garth L Nicolson
- Department of Molecular Pathology, The Institute for Molecular Medicine, 16731 Gothard St. Huntington Beach, California, 92647, USA
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26
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Chahal CAA, Gottwald JA, St Louis EK, Xie J, Brady PA, Alhurani RE, Timm P, Thapa P, Mandrekar J, So EL, Olson JE, Ackerman MJ, Somers VK. QT prolongation in patients with index evaluation for seizure or epilepsy is predictive of all-cause mortality. Heart Rhythm 2021; 19:578-584. [PMID: 34775068 DOI: 10.1016/j.hrthm.2021.11.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 11/02/2021] [Accepted: 11/06/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Refractory epilepsy confers a considerable lifetime risk of sudden unexplained death in epilepsy (SUDEP). Mechanisms may overlap with sudden cardiac death (SCD), particularly regarding QTc prolongation. Guidelines in the United States do not mandate the use of electrocardiography (ECG) in diagnostic evaluation of seizures or epilepsy. OBJECTIVE The purpose of this study was to determine the frequency of ECG use and of QT prolongation, and whether QT prolongation predicts mortality in patients with seizures. METHODS We performed a retrospective cohort study including all patients seen at Mayo Clinic in Rochester, Minnesota, from January 1, 2000, to July 31, 2015, with index evaluation for seizure or epilepsy. Patients with an ECG were categorized by the presence of a prolonged QT interval with a primary endpoint of all-cause mortality after the 15-year observation period. RESULTS Optimal cutoff QT intervals most predictive of mortality were identified. Median age was 40.0 years. An ECG was obtained in 18,222 patients (57.4%). After patients with confounding ECG findings were excluded, primary prolonged QT intervals were seen in 223 cases (1.4%), similar to the general population. Kaplan-Meier analysis demonstrated a significant increase in mortality (Cox hazard ratio [HR] 1.90; 95% confidence interval [CI] 1.76-2.05) for prolonged optimal cutoff QT, maintained after adjustments for age, Charlson comorbidity index, and sex (HR 1.48; 95% CI 1.37-1.59). CONCLUSION Use of ECG in diagnostic workup of patients with seizures is poor. A prolonged optimal cutoff QTc interval predicts all-cause mortality in patients evaluated for seizure and those diagnosed with epilepsy. We advocate the routine use of a 12-lead ECG at index evaluation in patients with seizure or epilepsy.
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Affiliation(s)
- C Anwar A Chahal
- Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Erik K St Louis
- Department of Neurology, Mayo Clinic, Rochester, Minnesota; Mayo Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jiang Xie
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Peter A Brady
- Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Rabe E Alhurani
- Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Neurology, Mayo Clinic, Rochester, Minnesota; Division of Geriatric Medicine, Loyola University Medical Center, Maywood, Illinois
| | - Paul Timm
- Department of Neurology, Mayo Clinic, Rochester, Minnesota; Mayo Center for Sleep Medicine, Mayo Clinic, Rochester, Minnesota
| | - Prabin Thapa
- Division of Biomedical Statistics and Informatics, Department of Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Jay Mandrekar
- Division of Biomedical Statistics and Informatics, Department of Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Elson L So
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
| | - Janet E Olson
- Division of Biomedical Statistics and Informatics, Department of Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Michael J Ackerman
- Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota; Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota; Department of Pediatrics, Mayo Clinic, Rochester, Minnesota
| | - Virend K Somers
- Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
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Rosso R, Hochstadt A, Viskin D, Chorin E, Schwartz AL, Tovia-Brodie O, Laish-Farkash A, Havakuk O, Gepstein L, Banai S, Viskin S. Polymorphic ventricular tachycardia, ischaemic ventricular fibrillation, and torsade de pointes: importance of the QT and the coupling interval in the differential diagnosis. Eur Heart J 2021; 42:3965-3975. [PMID: 33693589 DOI: 10.1093/eurheartj/ehab138] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/13/2021] [Accepted: 02/18/2021] [Indexed: 12/20/2022] Open
Abstract
AIMS Distinctive types of polymorphic ventricular tachycardia (VT) respond differently to different forms of therapy. We therefore performed the present study to define the electrocardiographic characteristics of different forms of polymorphic VT. METHODS AND RESULTS We studied 190 patients for whom the onset of 305 polymorphic VT events was available. The study group included 87 patients with coronary artery disease who had spontaneous polymorphic VT triggered by short-coupled extrasystoles in the absence of myocardial ischaemia. This group included 32 patients who had a long QT interval but nevertheless had their polymorphic VT triggered by ectopic beats with short coupling interval, a subcategory termed 'pseudo-torsade de pointes] (TdP). For comparison, we included 50 patients who had ventricular fibrillation (VF) during acute myocardial infarction ('ischaemic VF' group) and 53 patients with drug-induced TdP ('true TdP' group). The QT of patients with pseudo-TdP was (by definition) longer than that of patients with polymorphic VT and normal QT (QTc 491.4 ± 25.2 ms vs. 447.3 ± 55.6 ms, P < 0.001). However, their QT was significantly shorter than that of patients with true TdP (QTc 564.6 ± 75.6 ms, P < 0.001). Importantly, the coupling interval of the ectopic beat triggering the arrhythmia was just as short during pseudo-TdP as during polymorphic VT with normal QT (359.1 ± 38.1 ms vs. 356.6 ± 39.4 ms, P = 0.467) but was much shorter than during true TdP (581.2 ± 95.3 ms, P < 0.001). CONCLUSIONS The coupling interval helps discriminate between polymorphic VT that occurs despite a long QT interval (pseudo-TdP) and polymorphic arrhythmias striking because of a long QT (true TdP).
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Affiliation(s)
- Raphael Rosso
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Aviram Hochstadt
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Dana Viskin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Ehud Chorin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Arie Lorin Schwartz
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Oholi Tovia-Brodie
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Avishag Laish-Farkash
- Department of Cardiology, Assuta Ashdod University Hospital, Ha-Refu'a St 7, Ashdod 7747629, Israel
| | - Ofer Havakuk
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Lior Gepstein
- Department of Cardiology, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion-Israel institute of Technology, HaAliya HaShniya St 8, Haifa 3109601, Israel
| | - Shmuel Banai
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
| | - Sami Viskin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Weizmann St 6, Tel Aviv-Yafo 6423906, Israel
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28
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Affiliation(s)
- Peter J Schwartz
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.,Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Cusano Milanino (MI), Italy
| | - Hanno L Tan
- Department of Clinical and Experimental Cardiology, Amsterdam University Medical Center AMC, University of Amsterdam, Amsterdam, The Netherlands.,Netherlands Heart Institute, Utrecht, The Netherlands
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29
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Mantri N, Lu M, Zaroff JG, Risch N, Hoffmann T, Oni-Orisan A, Lee C, Jorgenson E, Iribarren C. QT Interval Dynamics and Cardiovascular Outcomes: A Cohort Study in an Integrated Health Care Delivery System. J Am Heart Assoc 2021; 10:e018513. [PMID: 34581201 PMCID: PMC8649135 DOI: 10.1161/jaha.120.018513] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.
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Affiliation(s)
- Neha Mantri
- Department of Cardiology Kaiser Permanente San Francisco Medical Center San Francisco CA
| | - Meng Lu
- Division of Research Kaiser Permanente Oakland CA
| | - Jonathan G Zaroff
- Department of Cardiology Kaiser Permanente San Francisco Medical Center San Francisco CA
| | - Neil Risch
- Institute for Human Genetics University of California, San Francisco CA
| | - Thomas Hoffmann
- Institute for Human Genetics University of California, San Francisco CA
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Viskin S, Chorin E, Viskin D, Hochstadt A, Schwartz AL, Rosso R. Polymorphic Ventricular Tachycardia: Terminology, Mechanism, Diagnosis, and Emergency Therapy. Circulation 2021; 144:823-839. [PMID: 34491774 DOI: 10.1161/circulationaha.121.055783] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Polymorphic ventricular tachyarrhythmias are highly lethal arrhythmias. Several types of polymorphic ventricular tachycardia have similar electrocardiographic characteristics but have different modes of therapy. In fact, medications considered the treatment of choice for one form of polymorphic ventricular tachycardia, are contraindicated for the other. Yet confusion about terminology, and thus diagnosis and therapy, continues. We present an in-depth review of the different forms of polymorphic ventricular tachycardia and propose a practical step-by-step approach for distinguishing these malignant arrhythmias.
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Affiliation(s)
- Sami Viskin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | - Ehud Chorin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | - Dana Viskin
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | - Aviram Hochstadt
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | - Arie Lorin Schwartz
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
| | - Raphael Rosso
- Department of Cardiology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Israel
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Castelletti S, Winkel BG, Schwartz PJ. Remote Monitoring of the QT Interval and Emerging Indications for Arrhythmia Prevention. Card Electrophysiol Clin 2021; 13:523-530. [PMID: 34330378 DOI: 10.1016/j.ccep.2021.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
QT interval prolongation is a marker of increased risk for life-threatening arrhythmias, and needs to be promptly recognized. Many effective drugs, however, prolong QTc (QT interval corrected for heart rate) in genetically predisposed subjects. The possibility of remote monitoring and QTc measurement for up to 2 weeks, continuously providing physicians with real time data, allows life-saving interventions or changes in drug therapy. This applies especially to patients with the long QT syndrome and to those taking drugs blocking the IKr current and prolonging the QT interval. Patch monitors recording ECG traces continuously are available and contribute to effective arrhythmic prevention.
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Affiliation(s)
- Silvia Castelletti
- Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Via Pier Lombardo 22, 20135 Milan, Italy
| | - Bo Gregers Winkel
- University Hospital Copenhagen, Rigshospitalet, Department of Cardiology, 2142 Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Peter J Schwartz
- Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Via Pier Lombardo 22, 20135 Milan, Italy.
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Young WJ, Warren HR, Mook-Kanamori DO, Ramírez J, van Duijvenboden S, Orini M, Tinker A, van Heemst D, Lambiase PD, Jukema JW, Munroe PB, Noordam R. Genetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank. CIRCULATION. GENOMIC AND PRECISION MEDICINE 2021; 14:e003231. [PMID: 33887147 PMCID: PMC8208093 DOI: 10.1161/circgen.120.003231] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 04/02/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND ECG markers of ventricular depolarization and repolarization are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian randomization (MR). METHODS Independent lead variants from a newly performed genome-wide association study for serum calcium in >300 000 European-ancestry participants from UK Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT, and QRS intervals using an inverse-weighted method in 76 226 participants not contributing to the serum calcium genome-wide association study. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR pleiotropy residual sum and outlier were performed to test for the presence of horizontal pleiotropy. RESULTS Two hundred five independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01 ms [95% CI, 2.03 to 3.99]) and JT (2.89 ms [1.91 to 3.87]) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. CONCLUSIONS These analyses support a causal effect of serum calcium levels on ventricular repolarization, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may, therefore, directly influence cardiovascular disease risk.
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Affiliation(s)
- William J. Young
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)
| | - Helen R. Warren
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- NIHR Barts Cardiovascular Biomedical Research Unit (H.R.W., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Dennis O. Mook-Kanamori
- Department of Clinical Epidemiology (D.O.M.-K.), Leiden University Medical Center, the Netherlands
- Department of Public Health and Primary Care (D.O.M.-K.), Leiden University Medical Center, the Netherlands
| | - Julia Ramírez
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)
| | - Stefan van Duijvenboden
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)
| | - Michele Orini
- Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)
- Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)
| | - Andrew Tinker
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- NIHR Barts Cardiovascular Biomedical Research Unit (H.R.W., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Diana van Heemst
- Department of Internal Medicine (D.v.H., R.N.), Leiden University Medical Center, the Netherlands
| | - Pier D. Lambiase
- Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trust (W.J.Y., M.O., P.D.L.)
- Institute of Cardiovascular Sciences, University of College London, United Kingdom (J.R., S.v.D., M.O., P.D.L.)
| | - J. Wouter Jukema
- Department of Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands
- Netherlands Heart Institute, Utrecht, the Netherlands (J.W.J.)
| | - Patricia B. Munroe
- Clinical Pharmacology Department, William Harvey Research Institute (W.J.Y., H.R.W., J.R., S.v.D., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
- NIHR Barts Cardiovascular Biomedical Research Unit (H.R.W., A.T., P.B.M.), Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Raymond Noordam
- Department of Internal Medicine (D.v.H., R.N.), Leiden University Medical Center, the Netherlands
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Schwartz PJ. 1970-2020: 50 years of research on the long QT syndrome-from almost zero knowledge to precision medicine. Eur Heart J 2021; 42:1063-1072. [PMID: 33057695 DOI: 10.1093/eurheartj/ehaa769] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/13/2020] [Accepted: 09/07/2020] [Indexed: 12/17/2022] Open
Abstract
To those of us involved in clinical research it seldom happens to begin working on a rather obscure disease, still largely unexplored, and to follow its ripening into a medical entity of large interest to clinicians and basic scientists alike, and moreover to do so for exactly 50 years. This is what has been my privilege in the relentless pursuit of the intriguing disease known as the long QT syndrome (LQTS). This essay begins with the encounter with my first patient affected by LQTS when just a handful of cardiologists had seen similar cases and continues with the series of efforts, some sound some amateurish, which eventually led-together with many brilliant partners and associates-to describe and understand the natural history of the disease and the most effective therapies. It then touches on how our International Registry for LQTS, with its well-documented family trees, constituted the necessary springboard for the major genetic discoveries of the 1990s. From the explosion of genetic data, my own interest focused first on the intriguing genotype-phenotype correlation and then on 'modifier genes', in the attempt of understanding why family members with the same disease-causing mutation could have an opposite clinical history. And from there on to iPS-derived cardiomyocytes, used to unravelling the specific mechanisms of action of modifier genes and to exploring novel therapeutic strategies. This long, and highly rewarding, journey continues because the fascination and the attraction of the unknown are irresistible.
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Affiliation(s)
- Peter J Schwartz
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Via Pier Lombardo, 22, Milan 20135, Italy
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Zhang S, Zhuang X, Lv Q, Du Z, Zhou H, Zhong X, Sun X, Xiong Z, Hu X, Yang D, Zhang M, Liao X. Six-Year Change in QT Interval Duration and Risk of Incident Heart Failure - A Secondary Analysis of the Atherosclerosis Risk in Communities Study. Circ J 2021; 85:640-646. [PMID: 33268658 DOI: 10.1253/circj.cj-20-0719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Few studies have investigated the association between temporal change in QT interval and incident heart failure (HF). The aim of this study is to examine this association in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS A secondary analysis was performed for the ARIC study. Overall, 10,274 participants (age 60.0±5.7 years, 45.7% male and 19.5% black) who obtained a 12-lead electrocardiography (ECG) at both Visit 1 (1987-1989) and Visit 3 (1993-1995) in the ARIC study were included. QT interval duration was corrected by using Bazett's formula (QTc). The change in corrected QT interval duration (∆QTc) was calculated by subtracting QTc at Visit 3 from Visit 1. The main outcome measure was incident HF. Multivariable Cox regression models were used to assess the association between ∆QTc and incident HF. During a median follow up of 19.5 years, 1,833 cases (17.8%) of incident HF occurred. ∆QTc was positively associated with incident HF (HR: 1.06, 95% CI 1.03, 1.08, per 10 ms increase, P<0.001; HR 1.22, 95% CI 1.08, 1.36, T3 vs. T1, P=0.002), after adjusting for traditional cardiovascular risk factor, QTc and QRS duration. CONCLUSIONS Temporal increases in QTc are independently associated with increased risk of HF.
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Affiliation(s)
- Shaozhao Zhang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiaodong Zhuang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Qiyuan Lv
- School of Nursing, Sun Yat-Sen University
| | - Zhimin Du
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Huimin Zhou
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiangbin Zhong
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xiuting Sun
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Zhenyu Xiong
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Xun Hu
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | - Daya Yang
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
| | | | - Xinxue Liao
- Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University
- NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University)
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Lee TL, Hsuan CF, Wu CC, Hung WC, Tsai IT, Wei CT, Yu TH, Lu IC, Chung FM, Lee YJ, Lu YC. Association between Triglyceride Glucose Index and Corrected QT Prolongation in Chinese Male Steelworkers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:4020. [PMID: 33921213 PMCID: PMC8069503 DOI: 10.3390/ijerph18084020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 01/08/2023]
Abstract
Objectives: Increased triglyceride glucose (TyG) index appears to be linked to carotid and coronary atherosclerosis and calcifications and possesses an elevated future risk of developing cardiovascular disease. Corrected QT (QTc) interval prolongation is associated with ventricular arrhythmias and sudden cardiac death, and a high prevalence of prolonged QTc interval was previously reported in blue-collar workers. The purpose of this study was to find the possible causal inter-relationship between TyG index and QTc interval in a large population of Chinese male steelworkers. Methods: A total of 3189 male workers from two steel plants were enrolled. They responded to a cross-sectional questionnaire on basic attributes and lifestyle, including sleep patterns. All workers in the two plants underwent periodic health checkups, including twelve-lead electrocardiography. Structural equation modeling (SEM) was used to assess the direct and indirect effects of TyG index on QTc interval. Results: With increasing TyG index tertile, the male steelworkers had an increased QTc interval. Applying multivariate analysis, TyG index was associated independently with the odds of QTc prolongation (adjusted odds ratio = 2.73, 95% confidence interval = 1.39-5.24, p = 0.004). SEM revealed that TyG index, hypertension, obesity, lifestyle, white blood cell (WBC) count, and liver function had statistically significant direct effects on QTc interval. Furthermore, TyG index also had an indirect effect on QTc interval through hypertension, obesity, WBC count, and liver function. Moreover, lifestyle had an indirect effect on QTc interval through TyG index. The final model explained 14% of the variability in QTc interval. Conclusions: An increased TyG index was associated with QTc interval prolongation in this study, and SEM delineated possible causal pathways and inter-relationships of the risk factors contributing to the occurrence of QTc prolongation among Chinese male steelworkers.
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Affiliation(s)
- Thung-Lip Lee
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - Chin-Feng Hsuan
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - I-Ting Tsai
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Department of Emergency, E-Da Hospital, Kaohsiung 82445, Taiwan
| | - Ching-Ting Wei
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung 82445, Taiwan
- Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan
- Department of Electrical Engineering, I-Shou University, Kaohsiung 82445, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - I-Cheng Lu
- Department of Occupational Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan;
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
| | - Yau-Jiunn Lee
- Lee’s Endocrinologic Clinic, Pingtung 90000, Taiwan;
| | - Yung-Chuan Lu
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
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Peralta AA, Schwartz J, Gold DR, Coull B, Koutrakis P. Associations between PM 2.5 metal components and QT interval length in the Normative Aging Study. ENVIRONMENTAL RESEARCH 2021; 195:110827. [PMID: 33549618 PMCID: PMC7987821 DOI: 10.1016/j.envres.2021.110827] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/15/2021] [Accepted: 01/28/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Several studies have found associations between increases in QT interval length, a marker of cardiac electrical instability, and short-term fine particulate matter (PM2.5) exposures. To our knowledge, this is the first study to examine the association between specific PM2.5 metal components and QT interval length. METHODS We measured heart-rate corrected QT interval (QTc) duration among 630 participants in the Normative Aging Study (NAS) based in Eastern Massachusetts between 2000 and 2011. We utilized time-varying linear mixed-effects regressions with a random intercept for each participant to analyze associations between QTc interval and moving averages (0-7 day moving averages) of 24-h mean concentrations of PM2.5 metal components (vanadium, nickel, copper, zinc and lead) measured at the Harvard Supersite monitoring station. Models were adjusted for daily PM2.5 mass estimated at a 1 km × 1 km grid cell from a previously validated prediction model and other covariates. Bayesian kernel machine regression (BKMR) was utilized to assess the overall joint effect of the PM2.5 metal components. RESULTS We found consistent results with higher lead (Pb) associated with significant higher QTc intervals for both the multi-pollutant and the two pollutant (PM2.5 mass and a PM2.5 component) models across the moving averages. The greatest effect of lead on QTc interval was detected for the 4-day moving average lead exposure. In the multi-pollutant model, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with a 7.91 ms (95% CI: 3.63, 12.18) increase in QTc interval. In the two-pollutant models with PM2.5 mass and lead, each 2.72 ng/m3 increase in daily lead levels for a 4-day moving average was associated with an 8.50 ms (95% CI: 4.59, 12.41) increase in QTc interval. We found that 4-day moving average of copper has a negative association with QTc interval when compared to the other PM2.5 metal components. In the multi-pollutant model, each 1.81 ng/m3 increase in daily copper levels for a 4-day moving average was associated with an -3.89 ms (95% CI: -6.98, -0.79) increase in QTc interval. Copper's essential function inside the human body could mediate its cardiotoxicity on cardiac conductivity and explain why we found that copper in comparison to the other metals was less harmful for QTc interval. CONCLUSIONS Exposure to metals contained in PM2.5 are associated with acute changes in ventricular repolarization as indicated by QT interval characteristics.
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Affiliation(s)
- Adjani A Peralta
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
| | - Joel Schwartz
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
| | - Diane R Gold
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
| | - Brent Coull
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Petros Koutrakis
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States
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Hekkanen JJ, Kenttä TV, Haukilahti MAE, Rahola JT, Holmström L, Vähätalo J, Tulppo MP, Kiviniemi AM, Pakanen L, Ukkola OH, Junttila MJ, Huikuri HV, Perkiömäki JS. Increased Beat-to-Beat Variability of T-Wave Heterogeneity Measured From Standard 12-Lead Electrocardiogram Is Associated With Sudden Cardiac Death: A Case-Control Study. Front Physiol 2020; 11:1045. [PMID: 32982784 PMCID: PMC7477294 DOI: 10.3389/fphys.2020.01045] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/29/2020] [Indexed: 11/13/2022] Open
Abstract
Introduction The prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization measured from standard 12-lead ECG is not well-understood. Methods We measured the short-term variability of repolarization parameters, such as T-wave heterogeneity in leads V4–V6 (TWH) and QT interval (QT), from five consecutive beats of previously recorded standard 12-lead ECG in 200 victims of unexpected sudden cardiac death (SCD) confirmed to be due to complicated atherosclerotic coronary artery disease (CAD) in medico-legal autopsy and 200 age- and sex-matched controls with angiographically confirmed CAD. The short-term variability of repolarization heterogeneity was defined as the standard deviation (SD) of the measured repolarization parameters. All ECGs were in sinus rhythm, and no premature ventricular contractions were included in the measured segment. Results TWH-SD and QT-SD were significantly higher in SCD victims than in subjects with CAD (6.9 ± 5.6 μV vs. 3.8 ± 2.6 μV, p = 1.8E-11; 8.3 ± 13.1 ms vs. 3.8 ± 7.1 ms, p = 0.00003, respectively). After adjusting in the multivariate clinical model with factors, such as diabetes, RR interval, and beta blocker medication, TWH-SD and QT-SD retained their significant power in discriminating between the victims of SCD and the patients with CAD (p = 0.00003, p = 0.006, respectively). TWH-SD outperformed QT-SD in identifying the SCD victims among the study subjects (area under the curve in the receiver operating characteristics curve 0.730 vs. 0.679, respectively). Conclusion Increased short-term variability of repolarization heterogeneity measured from standard 12-lead ECG is associated with SCD.
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Affiliation(s)
- Jenni J Hekkanen
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Tuomas V Kenttä
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Mira Anette E Haukilahti
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Janne T Rahola
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Lauri Holmström
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Juha Vähätalo
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Mikko P Tulppo
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Antti M Kiviniemi
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Lasse Pakanen
- Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland.,Research Unit of Internal Medicine, Department of Forensic Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Olavi H Ukkola
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - M Juhani Junttila
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Heikki V Huikuri
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Juha S Perkiömäki
- Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
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Hansen J, Johnsen J, Nielsen JM, Sørensen CB, Elkjær CC, Jespersen NR, Bøtker HE. Impact of Administration Time and Kv7 Subchannels on the Cardioprotective Efficacy of Kv7 Channel Inhibition. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:2549-2560. [PMID: 32669836 PMCID: PMC7337438 DOI: 10.2147/dddt.s226406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 04/15/2020] [Indexed: 01/12/2023]
Abstract
Purpose The mechanism of cardioprotection by Kv7.1-5 (KCNQ1-5) channels inhibition by XE991 is unclear. We examined the impact of administration time on the cardioprotective efficacy of XE991, the involvement of key pro-survival kinases, and the importance of the Kv7 subchannels. Methods Isolated perfused rat hearts were divided into five groups: 1) vehicle, 2) pre-, 3) post- or 4) pre- and post-ischemic administration of XE991 or 5) chromanol 293B (Kv7.1 inhibitor) followed by infarct size quantification. HL-1 cells undergoing simulated ischemia/reperfusion were exposed to either a) vehicle, b) pre-, c) per-, d) post-ischemic administration of XE991 or pre-, per- and post-ischemic administration of e) XE991, f) Chromanol 293B or g) HMR1556 (Kv7.1 inhibitor). HL-1 cell injury was evaluated by propidium iodide/Hoechst staining. Pro-survival kinase activation of Akt, Erk and STAT3 in XE991-mediated HL-1 cell protection was evaluated using phosphokinase inhibitors. Kv7 subtype expression was examined by RT-PCR and qPCR. Results XE991, but not Chromanol 293B, reduced infarct size and improved hemodynamic recovery in all isolated heart groups. XE991 protected HL-1 cells when administered during simulated ischemia. Minor activation of the survival kinases was observed in cells exposed to XE991 but pharmacological inhibition of kinase activation did not reduce XE991-mediated protection. Kv7 subchannels 1-5 were all present in rat hearts but predominately Kv7.1 and Kv7.4 were present in HL-1 cells and selective Kv7.1 did not reduce ischemia/reperfusion injury. Conclusion The cardioprotective efficacy of XE991 seems to depend on its presence during ischemia and early reperfusion and do not rely on RISK (p-Akt and p-Erk) and SAFE (p-STAT3) pathway activation. The protective effect of XE991 seems mainly mediated through the Kv7.4 subchannel.
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Affiliation(s)
- Jan Hansen
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jacob Johnsen
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jan Møller Nielsen
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Charlotte Brandt Sørensen
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Casper Carlsen Elkjær
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Nichlas Riise Jespersen
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Hans Erik Bøtker
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Baldi E, Sechi GM, Mare C, Canevari F, Brancaglione A, Primi R, Klersy C, Palo A, Contri E, Ronchi V, Beretta G, Reali F, Parogni P, Facchin F, Rizzi U, Bussi D, Ruggeri S, Oltrona Visconti L, Savastano S. COVID-19 kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests. Eur Heart J 2020; 41:3045-3054. [PMID: 32562486 PMCID: PMC7337787 DOI: 10.1093/eurheartj/ehaa508] [Citation(s) in RCA: 176] [Impact Index Per Article: 35.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/18/2020] [Accepted: 06/03/2020] [Indexed: 01/08/2023] Open
Abstract
AIMS An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve. METHODS AND RESULTS We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001). CONCLUSION The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.
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Affiliation(s)
- Enrico Baldi
- Department of Molecular Medicine, Section of Cardiology, University of Pavia, Pavia, Italy
- Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Claudio Mare
- Azienda Regionale Emergenza Urgenza, Milan, Italy
| | - Fabrizio Canevari
- SOREU della Pianura, Azienda Regionale Emergenza Urgenza (AREU), Pavia, Italy
| | | | - Roberto Primi
- Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Catherine Klersy
- Service of Clinical Epidemiology and Biometry, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandra Palo
- AAT Pavia – Azienda Regionale Emergenza Urgenza (AREU), c/o Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Enrico Contri
- AAT Pavia – Azienda Regionale Emergenza Urgenza (AREU), c/o Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Vincenza Ronchi
- AAT Pavia – Azienda Regionale Emergenza Urgenza (AREU), c/o Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- ASST di Pavia, Pavia, Italy
| | - Giorgio Beretta
- AAT Lodi – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Lodi, Lodi, Italy
| | - Francesca Reali
- AAT Lodi – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Lodi, Lodi, Italy
| | - Pierpaolo Parogni
- AAT Mantova – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Mantua, Mantua, Italy
| | - Fabio Facchin
- Department of Molecular Medicine, Section of Cardiology, University of Pavia, Pavia, Italy
| | - Ugo Rizzi
- AAT Cremona – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Cremona, Cremona, Italy
| | - Daniele Bussi
- AAT Cremona – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Cremona, Cremona, Italy
| | - Simone Ruggeri
- AAT Mantova – Azienda Regionale Emergenza Urgenza (AREU), c/o ASST di Mantua, Mantua, Italy
| | | | - Simone Savastano
- Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Abstract
Sickle cell disease (SCD) is one of the most common hereditary hemoglobinopathies worldwide. It is a multisystem disease that causes considerable patient morbidity. Despite advances in medical treatment, cardiopulmonary complications remain the most common cause of death in individuals with SCD. A growing body of evidence has shown that SCD results in a spectrum of cardiovascular complications through a variety of mechanisms, including chronic hemolysis, local tissue hypoxia, increased oxidative stress, and autonomic instability. Herein, we will examine the pathophysiology of sickle cell vasculopathy and discuss the spectrum of cardiovascular sequelae of the disease, while highlighting the impact of SCD on the cardiovascular health of the patients.
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41
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Yan L, Jin J, Jiang S, Zhu W, Gao M, Zhao X, Yuan J. QTc Interval Predicts Disturbed Circadian Blood Pressure Variation. Open Med (Wars) 2020; 15:139-146. [PMID: 32190737 PMCID: PMC7065424 DOI: 10.1515/med-2020-0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 01/07/2020] [Indexed: 11/15/2022] Open
Abstract
Background The relationship between electrocardiographic evaluation and circadian blood pressure (BP) variation in young and middle-aged hypertensive patients remains unknown. Methods A total of 171 hypertensive patients were included in the study. First, patients were divided into a young and middle-aged group and an elderly group. The two groups were then separately classified into three subgroups on the basis of circadian variation of BP as dippers, non-dippers and reverse-dippers. The electrocardiographic evaluation was calculated from 12-lead electrocardiography (ECG). Results QTc intervals were shortest in the dippers and longest in the reverse-dippers in the young and middle-aged group (QTc dipper: 416.53±18.37ms; non-dipper: 438.30±29.71ms; reverse-dipper: 444.93±25.47ms; for dipper vs non-dipper, and dipper vs reverse-dipper P<0.05). QTc interval was found to be an independent risk factor for the non-dipper BP pattern (Odds ratio 1.049; 95% CI 1.01-1.089; P=0.012) and reverse-dipper BP pattern (Odds ratio 1.051; 95% CI 1.007-1.098; P=0.023) in young and middle-aged hypertensive patients. No significant differences in other ECG parameters were found among the three subgroups in the young and middle-aged group. Conclusion Our study suggested that QTc interval might serve as a risk factor for non-dipper BP pattern and reverse-dipper BP pattern in young and middle-aged hypertensive patients.
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Affiliation(s)
- Liyuan Yan
- Department of Cardiology, the First Affiliated Hospital of Soochow University, No.188, Shizi Road, Suzhou, 215006, Jiangsu, China
| | - Jianling Jin
- Department of Electrocardiography, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Shili Jiang
- Department of Electrocardiography, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Wei Zhu
- Department of Electrocardiography, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Meiwen Gao
- Department of Electrocardiography, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China
| | - Xin Zhao
- Department of Cardiology, the First Affiliated Hospital of Soochow University, No.188, Shizi Road, Suzhou, 215006, Jiangsu, China
| | - Jiamin Yuan
- Department of Cardiology, the First Affiliated Hospital of Soochow University, No.188, Shizi Road, Suzhou, 215006, Jiangsu, China
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ter Bekke RM, Volders PG. Haloperidol and sudden death in first acute myocardial infarction. IJC HEART & VASCULATURE 2020; 26:100482. [PMID: 32142077 PMCID: PMC7046527 DOI: 10.1016/j.ijcha.2020.100482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 02/03/2020] [Indexed: 12/03/2022]
Affiliation(s)
- Rachel M.A. ter Bekke
- Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands
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43
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Schwartz PJ, Gentilini D. Can genetics predict risk for sudden cardiac death? The relentless search for the Holy Grail. Eur Heart J 2019; 39:3970-3972. [PMID: 30188985 DOI: 10.1093/eurheartj/ehy508] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Peter J Schwartz
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy
| | - Davide Gentilini
- Istituto Auxologico Italiano, IRCCS, Molecular Biology Laboratory, Unit of Bioinformatic and Statistical Genomic, Cusano Milanino, Italy.,Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
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Abstract
Sudden cardiac death (SCD) accounts for ∼50% of mortality after myocardial infarction (MI). Most SCDs result from ventricular tachyarrhythmias, and the tachycardias that precipitate cardiac arrest result from multiple mechanisms. As a result, it is highly unlikely that any single test will identify all patients at risk for SCD. Current guidelines for use of implantable cardioverter-defibrillators (ICDs) to prevent SCD are based primarily on measurement of left ventricular ejection fraction (LVEF). Although reduced LVEF is associated with increased total cardiac mortality after MI, the focus of current guidelines on LVEF omits ∼50% of patients who die suddenly. In addition, there is no evidence of a mechanistic link between reduced LVEF and arrhythmias. Thus, LVEF is neither sensitive nor specific as a tool for post-MI risk stratification. Newer tests to screen for predisposition to ventricular arrhythmias and SCD examine abnormalities of ventricular repolarization, autonomic nervous system function, and electrical heterogeneity. These tests, as well as older methods such as programmed stimulation, the signal-averaged electrocardiogram, and spontaneous ventricular ectopy, do not perform well in patients with LVEF ≤30%. Recent observational studies suggest, however, that these tests may have greater utility in patients with LVEF >30%. Because SCD results from multiple mechanisms, it is likely that combinations of risk factors will prove more precise for risk stratification. Prospective trials that evaluate the performance of risk stratification schema to determine ICD use are necessary for cost-effective reduction of the incidence of SCD after MI.
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Affiliation(s)
- Jonathan W Waks
- Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.,Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; ;
| | - Alfred E Buxton
- Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.,Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; ;
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Marocolo M, Katayama PL, Meireles A, Barbosa Neto O. Combined effects of exercise training and high doses of anabolic steroids on cardiac autonomic modulation and ventricular repolarization properties in rats. Can J Physiol Pharmacol 2019; 97:1185-1192. [PMID: 31505126 DOI: 10.1139/cjpp-2019-0286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Several studies have reported that high doses of synthetic anabolic androgenic steroids (AAS) can have serious negative effects on health, including the cardiovascular system. The aim of this study was to evaluate the combined effects of AAS and exercise training on ventricular repolarization and cardiac autonomic modulation in rats. Male Wistar rats were allocated into 4 groups: sedentary rats treated with vehicle, sedentary rats treated with nandrolone decanoate, swimming-trained rats treated with vehicle, and swimming-trained rats treated with nandrolone decanoate. Ventricular repolarization was evaluated by electrocardiographic analysis of QT interval and QT dispersion. Cardiac autonomic modulation was assessed by heart rate variability. Our results show that AAS increased QT interval and QT dispersion in sedentary rats treated with nandrolone decanoate as compared to sedentary rats treated with vehicle, indicating AAS-induced ventricular repolarization abnormalities. When rats treated with nandrolone decanoate were subjected to concomitant exercise training, ventricular repolarization was normalized. On the other hand, AAS-induced reduction in cardiac parasympathetic modulation was not prevented by exercise training. In conclusion, AAS produced cardiac autonomic dysfunction and ventricular repolarization disturbances in rats. Combining an exercise training protocol during the AAS treatment attenuated the ventricular repolarization abnormalities and did not prevent cardiac autonomic dysfunction.
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Affiliation(s)
- Moacir Marocolo
- Physiology and Human Performance Research Group, Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil
| | - Pedro L Katayama
- Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, SP, Brazil
| | - Anderson Meireles
- Physiology and Human Performance Research Group, Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil
| | - Octávio Barbosa Neto
- Sport Sciences Department, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil
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Wang CP, Hsu CC, Hung WC, Yu TH, Wu CC, Tsai IT, Tang WH, Chung FM, Houng JY, Lee YJ, Lu YC. Plasma fatty acid-binding protein 4 (FABP4) level is associated with abnormal QTc interval in patients with stable angina and chronic kidney disease. BMC Cardiovasc Disord 2019; 19:153. [PMID: 31234795 PMCID: PMC6591904 DOI: 10.1186/s12872-019-1134-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 06/12/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD). METHODS This study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. RESULTS Patients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P < 0.0001). Statistically significant associations were observed between plasma FABP4 levels and QTc interval (β = 0.267, P < 0.0001). Using multivariate and trend analyses, a higher concentration of plasma FABP4 level was independently associated with QTc prolongation in patients with stable angina and CKD. CONCLUSION In this study, plasma FABP4 levels were significantly higher in the patients with an abnormal QTc interval and were correlated with QTc prolongation. Further studies are required to elucidate whether plasma FABP4 plays a role in the pathogenesis of QTc prolongation.
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Affiliation(s)
- Chao-Ping Wang
- Division of Cardiology, I-Shou University, Kaohsiung, 82445, Taiwan.,School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Wei-Chin Hung
- Division of Cardiology, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, I-Shou University, Kaohsiung, 82445, Taiwan
| | - I-Ting Tsai
- Department of Emergency, E-Da Hospital, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Wei-Hua Tang
- Division of Cardiology, Department of Internal Medicine, National Yang-Ming University Hospital, Yilan, 26058, Taiwan
| | - Fu-Mei Chung
- Division of Cardiology, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Jer-Yiing Houng
- Department of Nutrition, Institute of Biotechnology and Chemical Engineering, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan
| | - Yau-Jiunn Lee
- Lee's Endocrinologic Clinic, Pingtung, 90000, Taiwan
| | - Yung-Chuan Lu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, I-Shou University, No. 1, Yi-Da Rd, Jiau-Shu Village, Yan-Chao District, Kaohsiung, 82445, Taiwan. .,School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan.
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Pigolkin YI, Shilova MA, Zakharov SN, Sereda AP, Zholinskiy AV, Kruglova IV, Shigeev SV. [The sudden death among the young persons under effect of the different forms of physical loads]. Sud Med Ekspert 2019; 62:50-55. [PMID: 30724895 DOI: 10.17116/sudmed20196201150] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The present review of the literature publications concerns the problem of sudden death (SD) among the young persons under effect of the different forms of physical loads. The statistical data on the frequency of sudden death are presented together with information about risk factors of SD, the morphological substrates and structural changes that promote death coming. The cases of sudden death among the young persons associated with the amateur sports activities and the professional sport of records are presented. The role of physical exercises and psycho-emotional stresses in the development of the terminal processes is considered with special reference to the risk factors and genetic predisposition to sudden cardiac death, largely among male athletes. The questions of sudden death in connection with cardiac pathologies as its main causes are discussed.
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Affiliation(s)
- Yu I Pigolkin
- Department of Forensic Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russia, Moscow, Russia, 119435
| | - M A Shilova
- Department of Forensic Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russia, Moscow, Russia, 119435
| | - S N Zakharov
- Department of Forensic Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russia, Moscow, Russia, 119435
| | - A P Sereda
- Centre for Sports Medicine, Russian Federal Medico-Biological Agency of the Russia, Moscow, Russia, 123182
| | - A V Zholinskiy
- Centre for Sports Medicine, Russian Federal Medico-Biological Agency of the Russia, Moscow, Russia, 123182
| | - I V Kruglova
- Centre for Sports Medicine, Russian Federal Medico-Biological Agency of the Russia, Moscow, Russia, 123182
| | - S V Shigeev
- Bureau of Forensic Medical Expertise, Moscow Health, Moscow, Russia, 115516
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49
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Blackman AO, Sobral Neto J, Lima ML, Rodrigues TMA, Gomes OM. Assessment and clinical relevance of the dynamic parameters of ventricular repolarization in patients with grade I left ventricular diastolic dysfunction 1. Can J Physiol Pharmacol 2019; 97:577-580. [PMID: 30676775 DOI: 10.1139/cjpp-2018-0507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed the QT dispersion circadian variation, heart rate variability in the time and frequency domains, and dynamics of QT using a 12-lead Holter. In the diastolic dysfunction group, 8 (30%) patients had QT dispersion > 80 ms. One (3.8%) patient presented premature ventricular complex > 10/h. The comparison between the 2 groups showed that the difference between the standard deviation of normal-to-normal intervals and low frequency power in both groups was statistically significant. We therefore conclude that increased parameters of ventricular repolarization and depressed heart rate variability reflect an imbalance in autonomic responses in patients with grade I left ventricular diastolic dysfunction without cardiovascular symptoms, enabling the identification of patients that are at a higher risk for cardiovascular events.
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Affiliation(s)
- Antoinette Oliveira Blackman
- a Instituto Cardiovascular São Francisco de Assis - Hospital Servcor, Belo Horizonte, MG, Brazil.,b Centro de Avaliação Cardiológica de Brasília - Centrocard, Brasília, DF, Brazil.,c Faculdade de Medicina, Uniceub, Brasília, DF, Brazil
| | - José Sobral Neto
- b Centro de Avaliação Cardiológica de Brasília - Centrocard, Brasília, DF, Brazil
| | - Melchior Luiz Lima
- a Instituto Cardiovascular São Francisco de Assis - Hospital Servcor, Belo Horizonte, MG, Brazil
| | | | - Otoni Moreira Gomes
- a Instituto Cardiovascular São Francisco de Assis - Hospital Servcor, Belo Horizonte, MG, Brazil
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Schwartz PJ, Crotti L, George AL. Modifier genes for sudden cardiac death. Eur Heart J 2018; 39:3925-3931. [PMID: 30215713 PMCID: PMC6247660 DOI: 10.1093/eurheartj/ehy502] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 08/28/2018] [Indexed: 01/07/2023] Open
Abstract
Genetic conditions, even those associated with identical gene mutations, can present with variable clinical manifestations. One widely accepted explanation for this phenomenon is the existence of genetic factors capable of modifying the consequences of disease-causing mutations (modifier genes). Here, we address the concepts and principles by which genetic factors may be involved in modifying risk for cardiac arrhythmia, then discuss the current knowledge and interpretation of their contribution to clinical heterogeneity. We illustrate these concepts in the context of two important clinical conditions associated with risk for sudden cardiac death including a monogenic disorder (congenital long QT syndrome) in which the impact of modifier genes has been established, and a complex trait (life-threatening arrhythmias in acute myocardial infarction) for which the search for genetic modifiers of arrhythmic risk is more challenging. Advances in understanding the contribution of modifier genes to a higher or lower propensity towards sudden death should improve patient-specific risk stratification and be a major step towards precision medicine.
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Affiliation(s)
- Peter J Schwartz
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Via Pier Lombardo, 22, Milan, Italy
- Corresponding author. Tel: +39 02 55000408, Fax: +39 02 55000411, ;
| | - Lia Crotti
- Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Via Pier Lombardo, 22, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore, 48, Monza, Italy
- Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Piazzale Brescia 20, Milan, Italy
| | - Alfred L George
- Department of Pharmacology, Northwestern University Feinberg School of Medicine, Searle 8-510, East Superior Street, Chicago, IL, USA
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