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Waight MC, Fabbricatore D, Behr ER, Sohal M, Li AC, Saba MM. The Impact of Coronary Ischemia Assessment on Outcomes in Those With Scar-Dependent Ventricular Tachycardia. J Cardiovasc Electrophysiol 2025; 36:201-211. [PMID: 39547937 PMCID: PMC11726999 DOI: 10.1111/jce.16495] [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] [Received: 04/25/2024] [Revised: 10/02/2024] [Accepted: 10/29/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND Guidance and outcomes of coronary ischemia assessment (IA) in those with structural heart disease (SHD), presenting with monomorphic ventricular tachycardia (MMVT) is unclear. OBJECTIVES To assess the impact of IA on arrhythmic and non-arrhythmic outcomes in those with SHD. METHODS Patients presenting with MMVT over a 6-year period to a tertiary center were retrospectively analyzed. Propensity score-matched analysis was performed comparing those undergoing IA to those who did not. The primary endpoint was a composite of VT recurrence, appropriate ICD therapy, heart failure hospitalization, and death. Secondary analysis of the individual components of the composite was performed. Kaplan-Meier, univariate and multivariate analysis was performed to compare the two groups and derive predictors of poor outcomes. RESULTS Two hundred and seventeen patients (57.6% ICM) were analyzed. 55.8% underwent IA. Following propensity score-matching, 120 patients remained. At 12 months, freedom from the primary endpoint was 68.3% of those undergoing IA versus 43.3% who did not, p < 0.001, multivariate HR 0.56 (0.34-0.92). This was driven by a reduction in all-cause mortality, with a 12-month survival of 98.3% in those undergoing IA versus 86.5% in those not undergoing IA (p < 0.01). Coronary intervention was associated with a significantly higher event-free 12-month survival compared to those who did not undergo intervention (82.4% vs 51.5%, respectively, p = 0.01). CONCLUSIONS Patients with SHD presenting MMVT who undergo an IA have significantly improved freedom from VT recurrence, appropriate ICD therapies, HF hospitalization, and death compared to those who do not, driven by a reduction in mortality.
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Affiliation(s)
| | | | - Elijah R. Behr
- City St George's University of LondonLondonUK
- St George's University Hospitals NHS Foundation TrustLondonUK
| | - Manav Sohal
- St George's University Hospitals NHS Foundation TrustLondonUK
| | - Anthony C. Li
- City St George's University of LondonLondonUK
- St George's University Hospitals NHS Foundation TrustLondonUK
| | - Magdi M. Saba
- City St George's University of LondonLondonUK
- St George's University Hospitals NHS Foundation TrustLondonUK
- Cleveland Clinic of LondonLondonUK
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Omar R, Tavolacci SC, Liou L, Villavisanis DF, Broza YY, Haick H. Real-time prognostic biomarkers for predicting in-hospital mortality and cardiac complications in COVID-19 patients. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0002836. [PMID: 38446834 PMCID: PMC10917247 DOI: 10.1371/journal.pgph.0002836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 02/07/2024] [Indexed: 03/08/2024]
Abstract
Hospitalized patients with Coronavirus disease 2019 (COVID-19) are highly susceptible to in-hospital mortality and cardiac complications such as atrial arrhythmias (AA). However, the utilization of biomarkers such as potassium, B-type natriuretic peptide, albumin, and others for diagnosis or the prediction of in-hospital mortality and cardiac complications has not been well established. The study aims to investigate whether biomarkers can be utilized to predict mortality and cardiac complications among hospitalized COVID-19 patients. Data were collected from 6,927 hospitalized COVID-19 patients from March 1, 2020, to March 31, 2021 at one quaternary (Henry Ford Health) and five community hospital registries (Trinity Health Systems). A multivariable logistic regression prediction model was derived using a random sample of 70% for derivation and 30% for validation. Serum values, demographic variables, and comorbidities were used as input predictors. The primary outcome was in-hospital mortality, and the secondary outcome was onset of AA. The associations between predictor variables and outcomes are presented as odds ratio (OR) with 95% confidence intervals (CIs). Discrimination was assessed using area under ROC curve (AUC). Calibration was assessed using Brier score. The model predicted in-hospital mortality with an AUC of 90% [95% CI: 88%, 92%]. In addition, potassium showed promise as an independent prognostic biomarker that predicted both in-hospital mortality, with an AUC of 71.51% [95% Cl: 69.51%, 73.50%], and AA with AUC of 63.6% [95% Cl: 58.86%, 68.34%]. Within the test cohort, an increase of 1 mEq/L potassium was associated with an in-hospital mortality risk of 1.40 [95% CI: 1.14, 1.73] and a risk of new onset of AA of 1.55 [95% CI: 1.25, 1.93]. This cross-sectional study suggests that biomarkers can be used as prognostic variables for in-hospital mortality and onset of AA among hospitalized COVID-19 patients.
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Affiliation(s)
- Rawan Omar
- Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel
| | - Sooyun Caroline Tavolacci
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Lathan Liou
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Dillan F. Villavisanis
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Yoav Y. Broza
- Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel
| | - Hossam Haick
- Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel
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Yang S, Bi Y, Wei Y, Li W, Liu J, Mao T, Tang Y. Muscone attenuates susceptibility to ventricular arrhythmia by inhibiting NLRP3 inflammasome activation in rats after myocardial infarction. J Biochem Mol Toxicol 2023; 37:e23458. [PMID: 37455625 DOI: 10.1002/jbt.23458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 03/14/2023] [Accepted: 07/04/2023] [Indexed: 07/18/2023]
Abstract
Fibrosis and abnormal expression of connexin 43 (Cx43) in the ventricle play vital roles in ventricular arrhythmias (VAs) after myocardial infarction (MI). Muscone, an active monomer of heart-protecting musk pill, has various biological activities, but its effect on susceptibility to VAs in rats with MI has not been determined. In the present study, we investigated the effects of muscone on ventricular inflammation, fibrosis, Cx43 expression, and the occurrence of VAs after MI. An MI model was established by ligating the proximal left anterior descending coronary artery. Then, the MI model rats were administered muscone (2 mg/kg/day) or vehicle (saline)via intragastric injection for 14 days. Cardiac function was evaluated by echocardiography, and an in vivo electrophysiological study was performed on Day 14. Cardiac inflammation, fibrosis, and Cx43 expression were determined by histochemical analysis and western blot analysis. Our results indicated that muscone treatment significantly improved cardiac function and inhibited ventricular inflammation, fibrosis, and nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome activation. Electrocardiogrphy and electrophysiology studies showed that muscone shortened the QRS interval, QT interval, QTc interval, and action potential duration; prolonged the effective refractory period; and reduced susceptibility to VAs in rats after MI. Furthermore, Cx43 expression in the BZ was increased by muscone treatment, and this change was coupled by inhibition of the NLRP3/IL-1β/p38 MAPK pathway. Taken together, our results demonstrated that muscone reduces susceptibility to VA, mainly by decreasing ventricular inflammation and fibrosis, and attenuates abnormal Cx43 expression by inhibiting NLRP3 inflammasome activation after myocardial infarction in rats.
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Affiliation(s)
- Shuang Yang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, People's Republic of China
| | - Yingying Bi
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, People's Republic of China
| | - Yanzhao Wei
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, People's Republic of China
| | - Wei Li
- Department of Cardiology, Wuhan No. 1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, People's Republic of China
| | - Jiangwen Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, People's Republic of China
| | - Tuohua Mao
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Yanhong Tang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- Cardiovascular Research Institute, Wuhan University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, People's Republic of China
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Schismenos V, Tzanis AA, Papadopoulos GE, Nikas D, Koniari I, Kolettis TM. Autonomic Responses During Acute Anterior Versus Inferior Myocardial Infarction: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e48893. [PMID: 38106761 PMCID: PMC10725181 DOI: 10.7759/cureus.48893] [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] [Accepted: 11/16/2023] [Indexed: 12/19/2023] Open
Abstract
Autonomic responses elicited by myocardial infarction vary depending on the site of injury, but accurate assessment using heart rate variability during the acute phase is limited. We systematically searched PubMed without language restrictions throughout July 2023. We reviewed studies reporting autonomic indices separately for anterior and inferior infarcts, followed by a meta-analysis of those reporting the standard deviation of the inter-beat interval between normal sinus beats during the initial 24 hours after the onset of symptoms. Six studies were included, comprising 341 patients (165 anterior, 176 inferior infarcts), all with satisfactory scores on the Newcastle-Ottawa quality scale. The estimated average of the standardized mean difference (based on the random-effects model) was -0.722 (95% confidence intervals: -0.943 to -0.501), which differed from zero (z=-6.416, p<0.0001). This finding indicates sympathetic and vagal dominance during acute anterior and inferior infarcts, respectively, with excessive responses likely contributing to early arrhythmogenesis. Despite the amelioration of autonomic dysfunction by revascularization, infarct location should be considered when commencing β-adrenergic receptor blockade, especially after delayed procedures.
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Affiliation(s)
| | | | | | - Dimitrios Nikas
- 1st Department of Cardiology, University Hospital of Ioannina, Ioannina, GRC
| | - Ioanna Koniari
- Electrophysiology and Device Department, University Hospital of South Manchester NHS Foundation Trust, Manchester, GBR
| | - Theofilos M Kolettis
- Cardiology, Cardiovascular Research Institute, Ioannina, GRC
- Cardiology, University of Ioannina, Ioannina, GRC
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5
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Wang C, Hao W. Cardiac arrhythmia and immune response in COVID-19 patients. Allergol Immunopathol (Madr) 2023; 51:63-70. [PMID: 37422781 DOI: 10.15586/aei.v51i4.883] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 04/15/2023] [Indexed: 07/11/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has presented substantial challenges for providing health care due to the numerous complications on the respiratory and cardiovascular systems of people. Cardiac arrhythmia is one of the cardiac complications, and it was observed in COVID-19 patients. Moreover, arrhythmia and cardiac arrest are common in COVID-19 patients in the intensive care unit. The occurrence of cardiac arrhythmia in COVID-19 patients is associated with hypoxia, cytokine storm, myocardial ischemia and inflammatory disease such as congestive heart failure. It is necessary to know the occurrence and mechanisms of tachyarrhythmia and bradyarrhythmia in patients with COVID-19 infection for their proper management. This review provides an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms.
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Affiliation(s)
- Chunlian Wang
- Institute for Prevention and Control of Chronic Non-communicable Diseases, Harbin Center for Disease Control and Prevention, Harbin, China
| | - Wenqiang Hao
- The Second Ward of Internal Medicine, The Second Hospital of Heilongjiang Province, Harbin, China; ;
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Baggett BC, Murphy KR, Sengun E, Mi E, Cao Y, Turan NN, Lu Y, Schofield L, Kim TY, Kabakov AY, Bronk P, Qu Z, Camelliti P, Dubielecka P, Terentyev D, del Monte F, Choi BR, Sedivy J, Koren G. Myofibroblast senescence promotes arrhythmogenic remodeling in the aged infarcted rabbit heart. eLife 2023; 12:e84088. [PMID: 37204302 PMCID: PMC10259375 DOI: 10.7554/elife.84088] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 05/18/2023] [Indexed: 05/20/2023] Open
Abstract
Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. Senescent cells interfere with cardiac function and outcome post-MI with age, but studies have not been performed in larger animals, and the mechanisms are unknown. Specifically, age-associated changes in timecourse of senescence and related changes in inflammation and fibrosis are not well understood. Additionally, the cellular and systemic role of senescence and its inflammatory milieu in influencing arrhythmogenesis with age is not clear, particularly in large animal models with cardiac electrophysiology more similar to humans than previously studied animal models. Here, we investigated the role of senescence in regulating inflammation, fibrosis, and arrhythmogenesis in young and aged infarcted rabbits. Aged rabbits exhibited increased peri-procedural mortality and arrhythmogenic electrophysiological remodeling at the infarct border zone (IBZ) compared to young rabbits. Studies of the aged infarct zone revealed persistent myofibroblast senescence and increased inflammatory signaling over a 12-week timecourse. Senescent IBZ myofibroblasts in aged rabbits appear to be coupled to myocytes, and our computational modeling showed that senescent myofibroblast-cardiomyocyte coupling prolongs action potential duration (APD) and facilitates conduction block permissive of arrhythmias. Aged infarcted human ventricles show levels of senescence consistent with aged rabbits, and senescent myofibroblasts also couple to IBZ myocytes. Our findings suggest that therapeutic interventions targeting senescent cells may mitigate arrhythmias post-MI with age.
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Affiliation(s)
- Brett C Baggett
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Kevin R Murphy
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Elif Sengun
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
- Department of Pharmacology, Institute of Graduate Studies in Health Sciences, Istanbul UniversityIstanbulTurkey
| | - Eric Mi
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Yueming Cao
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Nilufer N Turan
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Yichun Lu
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Lorraine Schofield
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Tae Yun Kim
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Anatoli Y Kabakov
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Peter Bronk
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | - Zhilin Qu
- School of Medicine, University of California, Los AngelesLos AngelesUnited States
| | - Patrizia Camelliti
- School of Biosciences and Medicine, University of SurreyGuildfordUnited Kingdom
| | - Patrycja Dubielecka
- Brown UniversityProvidenceUnited States
- Department of Hematology, Rhode Island HospitalProvidenceUnited States
| | - Dmitry Terentyev
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | | | - Bum-Rak Choi
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
| | | | - Gideon Koren
- Brown UniversityProvidenceUnited States
- Cardiovascular Research Center, Rhode Island HospitalProvidenceUnited States
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Gaebel R, Lang C, Vasudevan P, Lührs L, de Carvalho KAT, Abdelwahid E, David R. New Approaches in Heart Research: Prevention Instead of Cardiomyoplasty? Int J Mol Sci 2023; 24:ijms24109017. [PMID: 37240361 DOI: 10.3390/ijms24109017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/10/2023] [Accepted: 05/17/2023] [Indexed: 05/28/2023] Open
Abstract
Cardiovascular diseases are the leading cause of death in industrialized nations. Due to the high number of patients and expensive treatments, according to the Federal Statistical Office (2017) in Germany, cardiovascular diseases account for around 15% of total health costs. Advanced coronary artery disease is mainly the result of chronic disorders such as high blood pressure, diabetes, and dyslipidemia. In the modern obesogenic environment, many people are at greater risk of being overweight or obese. The hemodynamic load on the heart is influenced by extreme obesity, which often leads to myocardial infarction (MI), cardiac arrhythmias, and heart failure. In addition, obesity leads to a chronic inflammatory state and negatively affects the wound-healing process. It has been known for many years that lifestyle interventions such as exercise, healthy nutrition, and smoking cessation drastically reduce cardiovascular risk and have a preventive effect against disorders in the healing process. However, little is known about the underlying mechanisms, and there is significantly less high-quality evidence compared to pharmacological intervention studies. Due to the immense potential of prevention in heart research, the cardiologic societies are calling for research work to be intensified, from basic understanding to clinical application. The topicality and high relevance of this research area are also evident from the fact that in March 2018, a one-week conference on this topic with contributions from top international scientists took place as part of the renowned "Keystone Symposia" ("New Insights into the Biology of Exercise"). Consistent with the link between obesity, exercise, and cardiovascular disease, this review attempts to draw lessons from stem-cell transplantation and preventive exercise. The application of state-of-the-art techniques for transcriptome analysis has opened new avenues for tailoring targeted interventions to very individual risk factors.
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Affiliation(s)
- Ralf Gaebel
- Department of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, Germany
- Department of Life, Light & Matter, Interdisciplinary Faculty, Rostock University, 18059 Rostock, Germany
| | - Cajetan Lang
- Department of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, Germany
- Department of Life, Light & Matter, Interdisciplinary Faculty, Rostock University, 18059 Rostock, Germany
| | - Praveen Vasudevan
- Department of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, Germany
- Department of Life, Light & Matter, Interdisciplinary Faculty, Rostock University, 18059 Rostock, Germany
| | - Larissa Lührs
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, Pelé Pequeno Prίncipe Research Institute & Pequeno Prίncipe Faculties, Ave. Silva Jardim, P.O. Box 80240-020, Curitiba 1632, Brazil
| | - Katherine Athayde Teixeira de Carvalho
- Advanced Therapy and Cellular Biotechnology in Regenerative Medicine Department, Pelé Pequeno Prίncipe Research Institute & Pequeno Prίncipe Faculties, Ave. Silva Jardim, P.O. Box 80240-020, Curitiba 1632, Brazil
| | - Eltyeb Abdelwahid
- Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, IL 60611, USA
| | - Robert David
- Department of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, Germany
- Department of Life, Light & Matter, Interdisciplinary Faculty, Rostock University, 18059 Rostock, Germany
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Shrestha AB, Mehta A, Pokharel P, Mishra A, Adhikari L, Shrestha S, Yadav RS, Khanal S, Sah R, Nowrouzi-Kia B, Padhi BK, Chattu VK. Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2023; 13:diagnostics13030491. [PMID: 36766599 PMCID: PMC9913936 DOI: 10.3390/diagnostics13030491] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/17/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
(1) Background: Long COVID syndrome is a significant cause of morbidity in COVID-19 patients who remain symptomatic with varied clinical presentations beyond three weeks. Furthermore, the relevance of considering cardiovascular outcomes in post-COVID-19 syndrome is important in the current COVID-19 pandemic; (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review and meta-analysis. Systematic searches were conducted from multiple databases without language restrictions until October 8, 2022, to find studies evaluating cardiovascular outcomes such as arrhythmias, myocardium and pericardium diseases, coronary vessel disease, and thromboembolic disorders in post-COVID cases. The pooled odds ratio (OR), and standard mean difference (SMD) with their corresponding 95% confidence intervals (CI) were computed to find the association; (3) Results: Altogether, seven studies with a total of 8,126,462 (cases: 1,321,305; controls: 6,805,157) participants were included in the meta-analysis. Pooled odds ratios of cardiovascular outcomes were significantly higher in post-COVID cases (OR > 1, p < 0.05) than in controls. However, the mortality (OR: 4.76, p = 0.13), and heart rate variability (SMD: -0.06, p = 0.91) between cases and controls were not statistically significant; (4) Conclusions: Significant cardiovascular sequelae in long COVID syndrome highlight the importance of careful cardiac monitoring of COVID-19 patients in the post-COVID phase to address cardiovascular complications as soon as possible; larger-scale prospective studies are required for accurate estimation.
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Affiliation(s)
- Abhigan Babu Shrestha
- Department of Internal Medicine, M Abdur Rahim Medical College, Dinajpur 5200, Bangladesh
| | - Aashna Mehta
- Faculty of Medicine, University of Debrecen, 4008 Debrecen, Hungary
| | - Pashupati Pokharel
- Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 44613, Nepal
| | - Aakash Mishra
- Department of Internal Medicine, Kathmandu Medical College and Teaching Hospital, Kathmandu 21266, Nepal
| | - Lukash Adhikari
- Department of Internal Medicine, Patan Academy of Health Sciences, Lagankhel, Lalitpur 26500, Nepal
| | - Sajina Shrestha
- Department of Internal Medicine, KIST Medical College, Patan 14142, Nepal
| | - Randhir Sagar Yadav
- College of Medicine Jacksonville Program, University of Florida, Gainesville, FL 32611, USA
| | - Surakshya Khanal
- Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 44613, Nepal
| | - Ranjit Sah
- Harvard Medical School, Boston, MA 02115, USA
- Department of Microbiology, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu 44613, Nepal
- Dr. D.Y. Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune 411037, India
- Correspondence: (R.S.); (V.K.C.); Tel.: +1-416-946-3249 (V.K.C.)
| | - Behdin Nowrouzi-Kia
- ReSTORE Lab, Department of Occupational Science and Occupational Therapy, University of Toronto, Toronto, ON M5S 2E8, Canada
| | - Bijaya Kumar Padhi
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India
| | - Vijay Kumar Chattu
- ReSTORE Lab, Department of Occupational Science and Occupational Therapy, University of Toronto, Toronto, ON M5S 2E8, Canada
- Department of Community Medicine, Faculty of Medicine, Datta Meghe Institute of Medical Sciences, Wardha 442107, India
- Center for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India
- Correspondence: (R.S.); (V.K.C.); Tel.: +1-416-946-3249 (V.K.C.)
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9
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Endothelin System and Ischemia-Induced Ventricular Tachyarrhythmias. Life (Basel) 2022; 12:life12101627. [PMID: 36295062 PMCID: PMC9605000 DOI: 10.3390/life12101627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/13/2022] [Accepted: 10/15/2022] [Indexed: 11/17/2022] Open
Abstract
Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth understanding of the underlying mechanisms. Sympathetic activation has long been known to play a key role in the pathophysiology of ischemia-induced arrhythmias, but the regulating factors remain under investigation. Several lines of evidence implicate the endothelin system (a family of three isopeptides and two specific receptors) as an important modulator of sympathetic activation in the setting of acute coronary syndromes. Such interaction is present in the heart and in the adrenal medulla, whereas less is known on the effects of the endothelin system on the central autonomic network. This article summarizes the current state-of-the-art, placing emphasis on early-phase arrhythmogenesis, and highlights potential areas of future research.
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Pramudyo M, Bijaksana TL, Yahya AF, Putra ICS. Novel scoring system based on clinical examination for prediction of in-hospital mortality in acute coronary syndrome patients: a retrospective cohort study. Open Heart 2022; 9:openhrt-2022-002095. [PMID: 36229139 PMCID: PMC9562746 DOI: 10.1136/openhrt-2022-002095] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 09/21/2022] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND This study aims to develop PADjadjaran Mortality in Acute coronary syndrome (PADMA) Score to predict in-hospital mortality in acute coronary syndrome (ACS) patients based on clinical examination only. Additionally, we also compared the predictive value of the PADMA Score with the Global Registry of Acute Coronary Events (GRACE), Canada Acute Coronary Syndrome (C-ACS), and The Portuguese Registry of Acute Coronary Syndromes (ProACS) risk scores. METHODS This retrospective cohort study included all ACS patients aged≥18 years who were admitted to Dr. Hasan Sadikin Central General Hospital from January 2018 to January 2022. Patients' demographic, comorbidities and clinical presentation data were collected and analysed using multivariate logistic regression to create two models of scoring system (probability and cut-off model) to predict in-hospital all-cause mortality. The area under the curve (AUC) among PADMA, GRACE, C-ACS and ProACS risk scores was compared using the fisher Z test. RESULTS Multivariate regression analysis of 1359 patients showed that older age, history of cerebrovascular disease, tachycardia, high Shock Index and Killip class III and IV were independent mortality predictors and included in the PADMA Score. PADMA Score ranged from 0 to 20, with a score≥5 that can predict all-cause mortality with 82.78% sensitivity and 72.35% specificity. The difference in AUC between PADMA and GRACE scores was insignificant (p=0.126). Moreover, the AUC of the PADMA Score was significantly higher compared with the C-ACS (p=0.002) and ProACS risk scores (p<0.001). CONCLUSION PADMA Score is a simple scoring system to predict in-hospital mortality in ACS patients. PADMA Score≥5 showed an accurate discriminative capability to predict in-hospital mortality, comparable with the GRACE Score and superior to C-ACS and ProACS scores.
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Affiliation(s)
- Miftah Pramudyo
- Department of Cardiology and Vascular Medicine, Padjadjaran University, Bandung, Jawa Barat, Indonesia
| | | | - Achmad Fauzi Yahya
- Department of Cardiology and Vascular Medicine, Padjadjaran University, Bandung, Jawa Barat, Indonesia
| | - Iwan Cahyo Santosa Putra
- Department of Cardiology and Vascular Medicine, Padjadjaran University, Bandung, Jawa Barat, Indonesia
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Mouram S, Pannone L, Gauthey A, Sorgente A, Vergara P, Bisignani A, Monaco C, Mojica J, Al Housari M, Miraglia V, Del Monte A, Paparella G, Ramak R, Overeinder I, Bala G, Almorad A, Ströker E, Sieira J, Brugada P, La Meir M, Chierchia GB, de Asmundis C. Incidence and Predictors of Cardiac Arrhythmias in Patients With COVID-19. Front Cardiovasc Med 2022; 9:908177. [PMID: 35811696 PMCID: PMC9257009 DOI: 10.3389/fcvm.2022.908177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/11/2022] [Indexed: 12/15/2022] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) is a systemic disease caused by severe acute respiratory syndrome coronavirus 2. Arrhythmias are frequently associated with COVID-19 and could be the result of inflammation or hypoxia. This study aimed to define the incidence of arrhythmias in patients with COVID-19 and to correlate arrhythmias with pulmonary damage assessed by computed tomography (CT). Methods All consecutive patients with a COVID-19 diagnosis hospitalized at Universitair Ziekenhuis Brussel, Belgium, between March 2020 and May 2020, were screened. All included patients underwent a thorax CT scan and a CT severity score, a semiquantitative scoring system of pulmonary damage, was calculated. The primary endpoint was the arrhythmia occurrence during follow-up. Results In this study, 100 patients were prospectively included. At a mean follow-up of 19.6 months, 25 patients with COVID-19 (25%) experienced 26 arrhythmic episodes, including atrial fibrillation in 17 patients, inappropriate sinus tachycardia in 7 patients, atrial flutter in 1 patient, and third-degree atrioventricular block in 1 patient. No ventricular arrhythmias were documented. Patients with COVID-19 with arrhythmias showed more often need for oxygen, higher oxygen maximum flow, longer QTc at admission, and worse damage at CT severity score. In univariate logistic regression analysis, significant predictors of the primary endpoint were: the need for oxygen therapy (odds ratio [OR] 4.59, 95% CI 1.44-14.67, p = 0.01) and CT severity score of pulmonary damage (OR per 1 point increase 1.25, 95% CI 1.11-1.4, p < 0.001). Conclusions In a consecutive cohort of patients with COVID-19 the incidence of cardiac arrhythmias was 25%. The need for oxygen therapy and CT severity score were predictors of arrhythmia occurrence during follow-up.
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Affiliation(s)
- Sahar Mouram
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Luigi Pannone
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Anaïs Gauthey
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Antonio Sorgente
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Pasquale Vergara
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Antonio Bisignani
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Cinzia Monaco
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Joerelle Mojica
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Maysam Al Housari
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Vincenzo Miraglia
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Alvise Del Monte
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Gaetano Paparella
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Robbert Ramak
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Ingrid Overeinder
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Gezim Bala
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Alexandre Almorad
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Erwin Ströker
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Juan Sieira
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Pedro Brugada
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Mark La Meir
- Department of Cardiac Surgery, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, Brussels, Belgium
| | - Gian Battista Chierchia
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
| | - Carlo de Asmundis
- Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Brussels, Belgium
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Abstract
Coronavirus disease 2019 (COVID-19) has encompassed the globe since it was first observed just under 2 years ago. Although the disease is predominantly a respiratory illness, there have been observed complications throughout the various organ systems. Namely, cardiovascular complications, and, more specifically, arrhythmic complications have been described throughout the pandemic in patients with COVID-19. Management of atrial arrhythmias, ventricular arrhythmias, and bradyarrhythmias in patients with COVID-19 infection has been largely guided by our prior experience in the management of these arrhythmias in similar patient populations without infection. However, this review aims to highlight the specific considerations as they pertain to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the various arrhythmic manifestations observed with this disease.
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Affiliation(s)
| | | | - Elaine Y. Wan
- Address reprint requests and correspondence: Dr Elaine Wan, MD, FACC, FAHA, FHRS, Esther Aboodi Associate Professor of Medicine, 622 W 168th St, PH 3-Center, New York, NY 10032.
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13
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Luo J, Shaikh JA, Huang L, Zhang L, Iqbal S, Wang Y, Liu B, Zhou Q, Ajmal A, Rizvi M, Ajmal M, Liu Y. Human Plasma Metabolomics Identify 9-cis-retinoic Acid and Dehydrophytosphingosine Levels as Novel biomarkers for Early Ventricular Fibrillation after ST-elevated Myocardial Infarction. Bioengineered 2022; 13:3334-3350. [PMID: 35094641 PMCID: PMC8974221 DOI: 10.1080/21655979.2022.2027067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The relevant metabolite biomarkers for risk prediction of early onset of ventricular fibrillation (VF) after ST-segment elevation myocardial infarction (STEMI) remain unstudied. Here, we aimed to identify these imetabolites and the important metabolic pathways involved, and explore whether these metabolites could be used as predictors for the phenotype. Plasma samples were obtained retrospectively from a propensity-score matched cohort including 42 STEMI patients (21 consecutive VF and 21 non-VF). Ultra-performance liquid chromatography and mass spectrometry in combination with a comprehensive analysis of metabolomic data using Metaboanalyst 5.0 version were performed. As a result, the retinal metabolism pathway proved to be the most discriminative for the VF phenotype. Furthermore, 9-cis-Retinoic acid (9cRA) and dehydrophytosphingosine proved to be the most discriminative biomarkers. Biomarker analysis through receiver operating characteristic (ROC) curve showed the 2-metabolite biomarker panel yielding an area under the curve (AUC) of 0.836. The model based on Monte Carlo cross-validation found that 9cRA had the greatest probability of appearing in the predictive panel of biomarkers in the model. Validation of model efficiency based on an ROC curve showed that the combination model constructed by 9cRA and dehydrophytosphingosine had a good predictive value for early-onset VF after STEMI, and the AUC was 0.884 (95% CI 0.714–1). Conclusively, the retinol metabolism pathway was the most powerful pathway for differentiating the post-STEMI VF phenotype. 9cRA was the most important predictive biomarker of VF, and a plasma biomarker panel made up of two metabolites, may help to build a potent predictive model for VF.
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Affiliation(s)
- Jieying Luo
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Faculty of Life Science and Medicine, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Junaid Ahmed Shaikh
- GKT School of Medical Education, Faculty of Life Science and Medicine, King’s College London, London SE1 IUL, UK
| | - Lei Huang
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Faculty of Life Science and Medicine, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Lei Zhang
- Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, China
| | - Shahid Iqbal
- GKT School of Medical Education, Faculty of Life Science and Medicine, King’s College London, London SE1 IUL, UK
| | - Yu Wang
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
| | - Bojiang Liu
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
| | - Quan Zhou
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
| | - Aisha Ajmal
- St George’s Hospital Medical School, St. George’s, University of London, Cranmer Terrace, London, SW17 0RE UK
| | - Maryam Rizvi
- GKT School of Medical Education, Faculty of Life Science and Medicine, King’s College London, London SE1 IUL, UK
| | - Maryam Ajmal
- GKT School of Medical Education, Faculty of Life Science and Medicine, King’s College London, London SE1 IUL, UK
| | - Yingwu Liu
- Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Faculty of Life Science and Medicine, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
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14
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Magnocavallo M, Vetta G, Della Rocca DG, Gianni C, Mohanty S, Bassiouny M, Di Lullo L, Del Prete A, Cirone D, Lavalle C, Chimenti C, Al-Ahmad A, Burkhardt JD, Gallinghouse GJ, Sanchez JE, Horton RP, Di Biase L, Natale A. Prevalence, Management, and Outcome of Atrial Fibrillation and Other Supraventricular Arrhythmias in COVID-19 Patients. Card Electrophysiol Clin 2022; 14:1-9. [PMID: 35221076 PMCID: PMC8783208 DOI: 10.1016/j.ccep.2021.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Michele Magnocavallo
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA; Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Giampaolo Vetta
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Domenico G Della Rocca
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA.
| | - Carola Gianni
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Sanghamitra Mohanty
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Mohamed Bassiouny
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Luca Di Lullo
- Department of Nephrology and Dialysis, L. Parodi - Delfino Hospital, Colleferro, Roma, Italy
| | | | | | - Carlo Lavalle
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Cristina Chimenti
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Amin Al-Ahmad
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - J David Burkhardt
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - G Joseph Gallinghouse
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Javier E Sanchez
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Rodney P Horton
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA
| | - Luigi Di Biase
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA; Albert Einstein College of Medicine at Montefiore Hospital, New York, NY, USA
| | - Andrea Natale
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA; Interventional Electrophysiology, Scripps Clinic, La Jolla, CA, USA; Department of Cardiology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
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15
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Pandat S, Zhu Z, Fuentes-Rojas S, Schurmann P. Arrhythmias in COVID-19. Methodist Debakey Cardiovasc J 2021; 17:73-82. [PMID: 34992725 PMCID: PMC8679991 DOI: 10.14797/mdcvj.1039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 09/17/2021] [Indexed: 12/15/2022] Open
Abstract
The coronavirus pandemic remains a major public health burden with multisystem disease manifestations. There has been an ongoing global effort to better understand the unique cardiovascular manifestations of this disease and its associated arrhythmias. In this review, we summarize the current data on incidence and outcomes of arrhythmias in the acute and convalescent period, possible pathophysiologic mechanisms, and medical management. Sinus bradycardia-reported in multiple observational studies in the acute infectious period-stands out as an unexpected inflammatory response. Atrial fibrillation has been noted as the most common pathologic arrhythmia and has been shown to be a poor prognostic marker in multiple cohorts. In the convalescent period, long-term complications such as postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia have been described.
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Affiliation(s)
- Summit Pandat
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US
| | - Zhihao Zhu
- Houston Methodist Hospital, Houston, Texas, US
| | - Stephanie Fuentes-Rojas
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US
| | - Paul Schurmann
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US
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16
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Varney JA, Dong VS, Tsao T, Sabir MS, Rivera AT, Ghula S, Moriles KE, Cherukuri ML, Fazal R, Azevedo CB, Mohamed RM, Jackson GR, Fleming SE, Rochez DE, Abbas KS, Shah JH, Minh LHN, Osman F, Rafla SM, Huy NT. COVID-19 and arrhythmia: An overview. J Cardiol 2021; 79:468-475. [PMID: 35074257 PMCID: PMC8632592 DOI: 10.1016/j.jjcc.2021.11.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/03/2021] [Accepted: 11/01/2021] [Indexed: 12/15/2022]
Abstract
Arrhythmias in COVID-19 patients are associated with hypoxia, myocardial ischemia, cytokines, inflammation, electrolyte abnormalities, pro-arrhythmic or QT-prolonging medications, and underlying heart conditions such as severe congestive heart failure, inherited arrhythmia syndromes, or congenital heart conditions. In the pediatric population, multisystem inflammatory syndrome can lead to cardiac injury and arrhythmias. In addition, arrhythmias and cardiac arrests are most prevalent in the critically ill intensive care unit COVID-19 patient population. This review presents an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms, existing knowledge of pro-arrhythmic factors, and results from studies in adult and pediatric COVID-19 populations, and the clinical implications.
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Affiliation(s)
- Joseph A Varney
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Vinh S Dong
- AU/UGA Medical Partnership, Internal Medicine, Athens, GA, USA
| | - Tiffany Tsao
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Mariam S Sabir
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Amanda T Rivera
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Suhaib Ghula
- The University of Buckingham School of Medicine, Buckingham, United Kingdom
| | | | | | - Rahim Fazal
- AU/UGA Medical Partnership, Internal Medicine, Athens, GA, USA
| | - Chelsea B Azevedo
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Rana Mk Mohamed
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Garrett R Jackson
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Shannon E Fleming
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | - Diana E Rochez
- American University of the Caribbean School of Medicine, Cupecoy, Sint Maarten
| | | | | | - Le Huu Nhat Minh
- University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
| | - Faizel Osman
- Department of Cardiology, University Hospital Coventry, Coventry, United Kingdom
| | - Samir M Rafla
- Department of Cardiology and Angiology, Alexandria University, Alexandria, Egypt
| | - Nguyen Tien Huy
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
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17
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Pashoutan S, Baradaran Shokouhi S. Reconstructed State Space Features for Classification of ECG Signals. J Biomed Phys Eng 2021; 11:535-550. [PMID: 34458201 PMCID: PMC8385217 DOI: 10.31661/jbpe.v0i0.1112] [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: 01/10/2019] [Accepted: 03/14/2019] [Indexed: 12/02/2022]
Abstract
Background: Cardiac arrhythmias are considered as one of the most serious health conditions; therefore, accurate and quick diagnosis of these conditions is highly paramount
for the electrocardiogram (ECG) signals. Moreover, are rather difficult for the cardiologists to diagnose with unaided eyes due to a close similarity of these signals in the time domain. Objective: In this paper, an image-based and machine learning method were presented in order to investigate the differences between the three cardiac arrhythmias of VF, VT, SVT and the normal signal. Material and Methods: In this simulation study, the ECG data used are collected from 3 databases, including Boston Beth University Arrhythmias Center, Creighton University,
and MIT-BIH. The proposed algorithm was implemented using MATLAB R2015a software and its simulation. At first, the signal is transmitted to the state
space using an optimal time delay. Then, the optimal delay values are obtained using the particle swarm optimization algorithm and normalized mutual information
criterion. Furthermore, the result is considered as a binary image. Then, 19 features are extracted from the image and the results are presented in the multilayer
perceptron neural network for the purpose of training and testing. Results: In order to classify N-VF, VT-SVT, N-SVT, VF-VT, VT-N-VF, N-SVT-VF, VT-VF-SVT and VT-VF-SVT-N in the conducted experiments, the accuracy rates
were determined at 99.5%, 100%, 94.98%, 100%,100%, 100%, 99.5%, 96.5% and 95%, respectively. Conclusion: In this paper, a new approach was developed to classify the abnormal signals obtained from an ECG such as VT, VF, and SVT compared to a normal signal.
Compared to Other related studies, our proposed system significantly performed better
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Affiliation(s)
- Soheil Pashoutan
- MSc, Department of Electrical, Iran University of Science and Technology, Tehran, Iran
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18
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Anastasiou G, Hatziagelaki E, Liberopoulos E. Could Dapagliflozin Attenuate COVID-19 Progression in High-Risk Patients With or Without Diabetes? Behind DARE-19 Concept. J Cardiovasc Pharmacol 2021; 78:e12-e19. [PMID: 34001719 PMCID: PMC8253377 DOI: 10.1097/fjc.0000000000001011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 02/20/2021] [Indexed: 02/06/2023]
Abstract
ABSTRACT Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.
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Affiliation(s)
- Georgia Anastasiou
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece; and
| | - Erifili Hatziagelaki
- Second Department of Internal Medicine, Research Institute and Diabetes Center, “Attikon” University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Liberopoulos
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece; and
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Affiliation(s)
- Rakesh Yadav
- Professor of Cardiology, Department of Cardiology, AIIMS, Ansari Nagar, New Delhi, 110029, India.
| | - Ragav Bansal
- Assitant Professor of Cardiology, Department of Cardiology, AIIMS, Ansari Nagar, New Delhi, 110029, India
| | - Sudhanshu Budakoty
- Department of Cardiology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India
| | - Parag Barwad
- Professor of Cardiology, Department of Cardiology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India
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20
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Dherange P, Lang J, Qian P, Oberfeld B, Sauer WH, Koplan B, Tedrow U. Arrhythmias and COVID-19: A Review. JACC Clin Electrophysiol 2020; 6:1193-1204. [PMID: 32972561 PMCID: PMC7417167 DOI: 10.1016/j.jacep.2020.08.002] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/31/2020] [Accepted: 08/04/2020] [Indexed: 12/15/2022]
Abstract
Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge. Cardiac arrhythmias are more common in critically ill COVID-19 patients. The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects. To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes. It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine. As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.
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Affiliation(s)
- Parinita Dherange
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Joshua Lang
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Pierre Qian
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Blake Oberfeld
- Division of Cardiovascular Medicine, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - William H Sauer
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Bruce Koplan
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Usha Tedrow
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction. Int J Mol Sci 2020; 21:ijms21030918. [PMID: 32019245 PMCID: PMC7037853 DOI: 10.3390/ijms21030918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 01/26/2020] [Accepted: 01/28/2020] [Indexed: 02/05/2023] Open
Abstract
Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.
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Lekkas P, Kontonika M, Georgiou ES, La Rocca V, Mouchtouri ET, Mourouzis I, Pantos C, Kolettis TM. Endothelin receptors in the brain modulate autonomic responses and arrhythmogenesis during acute myocardial infarction in rats. Life Sci 2019; 239:117062. [PMID: 31734261 DOI: 10.1016/j.lfs.2019.117062] [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: 08/30/2019] [Revised: 10/31/2019] [Accepted: 11/09/2019] [Indexed: 10/25/2022]
Abstract
AIMS Endothelin has been implicated in various processes in the brain, including the modulation of sympathetic responses. The present study examined the pathophysiologic role of brain endothelin-receptors in the setting of acute myocardial infarction, characterized by high incidence of ventricular tachyarrhythmias. MAIN METHODS We investigated the effects of intracerebroventricular administration of antagonists of endothelin-receptors ETA, ETB, or both, during a 24 h-observation period post-coronary ligation in (n = 70) rats. Continuous recording was performed via implanted telemetry transmitters, followed by arrhythmia-analysis and calculation of autonomic indices derived from heart rate variability. The regional myocardial electrophysiologic properties were assessed by monophasic action potentials and multi-electrode recordings. KEY FINDINGS Sympathetic-activity was decreased and vagal-activity was enhanced after intracerebroventricular ETA-receptor blockade, thus attenuating regional myocardial repolarization inhomogeneity. As a result, the incidence of ventricular tachyarrhythmias was markedly lower in this group. Such effects were also observed after intracerebroventricular blockade of ETB-, or both, ETA- and ETB-receptors, although to a lesser extent. SIGNIFICANCE ETA-receptors in the brain modulate sympathetic and vagal responses and alter arrhythmogenesis during evolving myocardial necrosis in rats. These findings provide insights into arrhythmogenic mechanisms during acute myocardial infarction and call for further investigation on the role of endothelin in the central autonomic network.
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Affiliation(s)
- Panagiotis Lekkas
- Cardiovascular Research Institute, Ioannina and Athens, Greece; Department of Physiology, Medical School, University of Ioannina, Greece
| | | | | | | | - Eleni-Taxiarchia Mouchtouri
- Cardiovascular Research Institute, Ioannina and Athens, Greece; Department of Cardiology, Medical School, University of Ioannina, Greece
| | - Iordanis Mourouzis
- Department of Pharmacology, Medical School, National & Kapodistrian University of Athens, Greece
| | - Constantinos Pantos
- Department of Pharmacology, Medical School, National & Kapodistrian University of Athens, Greece
| | - Theofilos M Kolettis
- Cardiovascular Research Institute, Ioannina and Athens, Greece; Department of Cardiology, Medical School, University of Ioannina, Greece.
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Lekkas P, Georgiou ES, Kontonika M, Mouchtouri ET, Mourouzis I, Pantos C, Kolettis TM. Intracerebroventricular endothelin receptor-A blockade in rats decreases phase-II ventricular tachyarrhythmias during acute myocardial infarction. Physiol Res 2019; 68:867-871. [PMID: 31424250 DOI: 10.33549/physiolres.934135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.
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Affiliation(s)
- P Lekkas
- Cardiovascular Research Institute, University of Ioannina, Ioannina, Greece.
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24
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Bellut H, Guillemet L, Bougouin W, Charpentier J, Ben Hadj Salem O, Llitjos JF, Paul M, Valade S, Spagnolo S, Lamhaut L, Chiche JD, Marijon E, Pène F, Varenne O, Mira JP, Dumas F, Cariou A. Early recurrent arrhythmias after out-of-hospital cardiac arrest associated with obstructive coronary artery disease: Analysis of the PROCAT registry. Resuscitation 2019; 141:81-87. [PMID: 31185259 DOI: 10.1016/j.resuscitation.2019.05.034] [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] [Received: 02/04/2019] [Revised: 05/23/2019] [Accepted: 05/29/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVE After out-of-hospital cardiac arrest (OHCA) associated with obstructive coronary artery disease (CAD), the risk of recurrence during the early period is unclear and the indication for anti-arrhythmic treatment is debated. We assessed the incidence and predisposing factors for severe cardiac arrhythmias in this population. DESIGN Retrospective study in a cardiac arrest center. SETTINGS The primary endpoint was the occurrence of major cardiac arrhythmias from hospital admission to intensive care unit (ICU) discharge in patients admitted after an OHCA associated with obstructive CAD. A major arrhythmia was defined as any arrhythmic event (auricular or ventricular) associated with cardiac arrest recurrence and/or severe arterial hypotension. Secondary outcomes were time from ICU admission to arrhythmia occurrence and all-cause in-ICU mortality. Risk factors for recurrence of a major arrhythmia were assessed using multivariate analysis. PATIENTS We included all consecutive OHCA patients resuscitated from ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as initial rhythm associated with obstructive CAD, and who had a successful primary percutaneous coronary intervention. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Among 256 patients, a major arrhythmia occurred in 29 (11.3%), within the first 24 h in 79.3% of cases and were mostly VF (44.8%). Mortality rate was significantly increased in patients with major arrhythmia recurrence (69% vs 41%; p = 0.006). Factor significantly associated with recurrence of severe arrhythmia was male gender (OR 0.32 [0.12-0.92]; p = 0.034). Treatment with prophylactic anti-arrhythmic in the ICU was not associated with a change in the risk of recurrence (OR 0.85 [0.21-3.65], p = 0.82). CONCLUSION An early recurrence of major arrhythmia was observed in more than 10% of post-cardiac arrest patients. These events happened mostly within the first 24 h. The interest of prophylactic anti-arrhythmic treatment remains to be evaluated in this population.
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Affiliation(s)
- Hugo Bellut
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France
| | - Lucie Guillemet
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France.
| | - Wulfran Bougouin
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
| | | | - Omar Ben Hadj Salem
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Jean-François Llitjos
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Marine Paul
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Sandrine Valade
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France
| | - Shirley Spagnolo
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France
| | - Lionel Lamhaut
- Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; SAMU 75, Necker Hospital (APHP), Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
| | - Jean-Daniel Chiche
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Eloi Marijon
- Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; Cardiology Department, European Georges Pompidou Hospital (APHP), Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
| | - Frédéric Pène
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Olivier Varenne
- Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; Cardiology Department, Cochin Hospital (APHP), Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
| | - Jean-Paul Mira
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France
| | - Florence Dumas
- Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; Emergency Department, Cochin Hospital (APHP), Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
| | - Alain Cariou
- Medical Intensive Care Unit, Cochin Hospital (APHP), Paris, France; Paris Descartes University, Sorbonne Paris Cité-Medical School, Paris, France; INSERM U970 (team 4), Paris Cardiovascular Research Centre, Paris, France
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25
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Kolettis TM, Kontonika M, Lekkas P, Vlahos AP, Baltogiannis GG, Gatzoulis KA, Chrousos GP. Autonomic responses during acute myocardial infarction in the rat model: implications for arrhythmogenesis. J Basic Clin Physiol Pharmacol 2018; 29:339-345. [PMID: 29634485 DOI: 10.1515/jbcpp-2017-0202] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 01/30/2018] [Indexed: 01/01/2023]
Abstract
Background Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. Methods The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. Results In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhythmias were frequent, displaying a bimodal curve, and motion counts were low. Vagal activity decreased early post-ligation, coinciding with a high incidence of tachyarrhythmias, but tended to rise subsequently in rats with higher motion counts. Sympathetic activity increased after the third hour, along with a second tachyarrhythmia peak, and remained elevated throughout the 24-h period. Conclusions Vagal withdrawal, followed by gradual sympathetic activation, may participate in arrhythmogenesis during acute myocardial infarction.
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Affiliation(s)
- Theofilos M Kolettis
- University of Ioannina, 1 Stavrou Niarxou Avenue, 45110 Ioannina, Greece.,Cardiovascular Research Institute, Ioannina, Greece
| | | | | | | | | | | | - George P Chrousos
- National and Kapodistrian University of Athens, Athens, Greece.,National Institutes of Health, Bethesda, MD, USA
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Kolettis TM. Autonomic function and ventricular tachyarrhythmias during acute myocardial infarction. World J Exp Med 2018; 8:8-11. [PMID: 30191139 PMCID: PMC6125141 DOI: 10.5493/wjem.v8.i1.8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 08/05/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023] Open
Abstract
Most cases of sudden cardiac death are attributed to sustained ventricular tachyarrhythmias (VTs), triggered by acute coronary occlusion. Autonomic dysfunction, an important arrhythmogenic mechanism in this setting, is being actively investigated, aiming at the advent of preventive strategies. Recent experimental studies have shown vagal withdrawal after anterior myocardial infarction, coinciding with high incidence of VTs, followed by more gradual sympathetic activation coinciding with a second arrhythmia peak. This article summarizes recent knowledge on this intriguing topic, generating hypotheses that can be investigated in future experimental and clinical studies.
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Affiliation(s)
- Theofilos M Kolettis
- Department of Cardiology, Cardiovascular Research Institute and University of Ioannina Medical School, Ioannina 45500, Greece
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27
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Kolettis TM, Bagli E, Barka E, Kouroupis D, Kontonika M, Vilaeti AD, Markou M, Roumpi M, Maltabe V, La Rocca V, Agathopoulos S, Fotsis T. Medium-term Electrophysiologic Effects of a Cellularized Scaffold Implanted in Rats After Myocardial Infarction. Cureus 2018; 10:e2959. [PMID: 30214847 PMCID: PMC6132679 DOI: 10.7759/cureus.2959] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Cardiac repair strategies are being evaluated for myocardial infarctions, but the safety issues regarding their arrhythmogenic potential remain unresolved. By utilizing the in-vivo rat model, we have examined the medium-term electrophysiologic effects of a biomaterial scaffold that has been cellularized with spheroids of human adipose tissue, derived from mesenchymal stem cells and umbilical vein endothelial cells. Methods Mesenchymal stem cells, which exhibit adequate differentiation capacity, were co-cultured with umbilical vein endothelial cells and were seeded on an alginate based scaffold. After in-vitro characterization, the cellularized scaffold was implanted in (n=15) adult Wistar rats 15 min post ligation of the left coronary artery, with an equal number of animals serving as controls. Two weeks thereafter, monophasic action potentials were recorded and activation-mapping was performed with a multi-electrode array. An arrhythmia score for inducible ventricular tachyarrhythmias was calculated after programmed electrical stimulation. Results The arrhythmia score was comparable between the treated animals and controls. No differences were detected in the local conduction at the infarct border and in the voltage rise in monophasic action potential recordings. Treatment did not affect the duration of local repolarization, but tended to enhance its dispersion. Conclusions The fabricated bi-culture cellularized scaffold displayed favorable properties after in-vitro characterization. Medium-term electrophysiologic assessment after implantation in the infarcted rat myocardium revealed low arrhythmogenic potential, but the long-term effects on repolarization dispersion will require further investigation.
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Affiliation(s)
| | - Eleni Bagli
- Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - Forth, Ioannina, GRC
| | - Eleonora Barka
- Ceramics and Composites Laboratory, Materials Science and Engineering, University of Ioannina, Ioannina, GRC
| | - Dimitrios Kouroupis
- Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - Forth, Ioannina, GRC
| | | | | | - Maria Markou
- Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - Forth, Ioannina, GRC
| | - Maria Roumpi
- Ceramics and Composites Laboratory, Science and Engineering, University of Ioannina, Ioannina, GRC
| | - Violetta Maltabe
- Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - Forth, Ioannina, GRC
| | | | - Simeon Agathopoulos
- Ceramics and Composites Laboratory, Materials Science and Engineering, University of Ioannina, Ioannina, GRC
| | - Theodore Fotsis
- Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - Forth, Ioannina, GRC
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28
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Gatzoulis KA, Arsenos P, Trachanas K, Dilaveris P, Antoniou C, Tsiachris D, Sideris S, Kolettis TM, Tousoulis D. Signal-averaged electrocardiography: Past, present, and future. J Arrhythm 2018; 34:222-229. [PMID: 29951136 PMCID: PMC6010001 DOI: 10.1002/joa3.12062] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 03/28/2018] [Indexed: 01/12/2023] Open
Abstract
Signal-averaged electrocardiography records delayed depolarization of myocardial areas with slow conduction that can form the substrate for monomorphic ventricular tachycardia. This technique has been examined mostly in patients with coronary artery disease, but its use has been declined over the years. However, several lines of evidence, derived from hitherto clinical data in patients with healed myocardial infarction, indicate that signal-averaged electrocardiography remains a valuable tool in risk stratification, especially when incorporated into algorithms encompassing invasive and noninvasive indices. Such an approach can aid the more precise identification of candidates for device therapy, in the context of primary prevention of sudden cardiac death. This article reappraises the value of signal-averaged electrocardiography as a predictor of arrhythmic outcome in patients with ischemic heart disease and discusses potential future indications.
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Affiliation(s)
- Konstantinos A. Gatzoulis
- Electrophysiology Laboratory and First University Department of CardiologyHippokration General HospitalNational and Kapodestrian University of AthensAthensGreece
| | - Petros Arsenos
- Electrophysiology Laboratory and First University Department of CardiologyHippokration General HospitalNational and Kapodestrian University of AthensAthensGreece
| | | | - Polychronis Dilaveris
- Electrophysiology Laboratory and First University Department of CardiologyHippokration General HospitalNational and Kapodestrian University of AthensAthensGreece
| | - Christos Antoniou
- Electrophysiology Laboratory and First University Department of CardiologyHippokration General HospitalNational and Kapodestrian University of AthensAthensGreece
| | | | - Skevos Sideris
- Department of CardiologyHippokration General HospitalAthensGreece
| | - Theofilos M. Kolettis
- Department of CardiologyUniversity of IoanninaIoanninaGreece
- Cardiovascular Research InstituteIoanninaGreece
| | - Dimitrios Tousoulis
- Electrophysiology Laboratory and First University Department of CardiologyHippokration General HospitalNational and Kapodestrian University of AthensAthensGreece
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Singh JA, Cleveland J. Allopurinol and the risk of ventricular arrhythmias in the elderly: a study using US Medicare data. BMC Med 2017; 15:59. [PMID: 28327188 PMCID: PMC5361697 DOI: 10.1186/s12916-017-0816-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 02/10/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There are no published human studies investigating whether the use of allopurinol, the most commonly used medication for the treatment of hyperuricemia in gout, the most common type of inflammatory arthritis in adults, has any beneficial effects on ventricular electrophysiology. The objective of our study was to assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA). METHODS We used the 5% random sample of Medicare beneficiaries from 2006-2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, sex), comorbidity, cardiac medications, and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI). RESULTS Of the 28,755 episodes of new allopurinol use, 2538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, 75% had gout as the underlying diagnosis, and the mean Charlson-Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1-180 days, 151; 181 days to 2 years, 105; and > 2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76-0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1-180 days, 0.96 (95% CI, 0.85-1.08); 181 days to 2 years, 0.76 (95% CI, 0.68-0.85); and > 2 years, 0.72 (95% CI, 0.60-0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates. CONCLUSION Allopurinol use and use duration of more than 6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA. .,Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL, USA. .,Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. .,University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
| | - John Cleveland
- Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.,University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL, 35294, USA
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30
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Gatzoulis KA, Sideris A, Kanoupakis E, Sideris S, Nikolaou N, Antoniou CK, Kolettis TM. Arrhythmic risk stratification in heart failure: Time for the next step? Ann Noninvasive Electrocardiol 2017; 22. [PMID: 28252256 DOI: 10.1111/anec.12430] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 01/10/2017] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Primary prevention of sudden cardiac death by means of implantable cardioverter-defibrillators constitutes the holy grail of arrhythmology. However, current risk stratification algorithms lead to suboptimal outcomes, by both allocating ICDs to patients not deriving any meaningful survival benefit and withholding them from those erroneously considered as low-risk for arrhythmic mortality. METHODS In the present review article we will attempt to present shortcomings of contemporary guidelines regarding sudden death prevention in ischemic and dilated cardiomyopathy patients and present available data suggesting encouraging results following implementation of multifactorial approaches, by using multiple modalities, both noninvasive and invasive. Invasive electrophysiological testing, namely programmed ventricular stimulation, will be discussed in greater length to highlight both its potential usefulness and currently ongoing multicenter studies aiming to provide evidence necessary to make the next step in sudden death risk stratification. RESULTS Promising findings have been reported by multiple study groups regarding novel strategies for both negative selection of low and positive selection of relatively preserved ejection fraction patients as candidates for ICD implantation. CONCLUSIONS The era of ejection fraction as the sole risk stratifier for arrhythmic risk in heart failure appears to be drawing to an end, especially if current underway large studies validate previous findings.
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Affiliation(s)
- Konstantinos A Gatzoulis
- Electrophysiology Laboratory, First Department of Cardiology, "Hippokration" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Antonios Sideris
- Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, "Evangelismos" General Hospital of Athens, Athens, Greece
| | - Emmanuel Kanoupakis
- Department of Cardiology, University General Hospital of Heraklion, Heraklion, Greece
| | - Skevos Sideris
- State Department of Cardiology, "Hippokration" General Hospital, Athens, Greece
| | - Nikolaos Nikolaou
- Department of Cardiology, "Konstantopouleio" General Hospital, Athens, Greece
| | - Christos-Konstantinos Antoniou
- Electrophysiology Laboratory, First Department of Cardiology, "Hippokration" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theofilos M Kolettis
- Department of Cardiology, University General Hospital of Ioannina, Ioannina, Greece
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31
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Kontonika M, Barka E, Roumpi M, La Rocca V, Lekkas P, Daskalopoulos EP, Vilaeti AD, Baltogiannis GG, Vlahos AP, Agathopoulos S, Kolettis TM. Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats. Growth Factors 2017; 35:1-11. [PMID: 28264596 DOI: 10.1080/08977194.2017.1297432] [Citation(s) in RCA: 4] [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] [Indexed: 12/31/2022]
Abstract
Experimental studies indicate improved ventricular function after treatment with growth hormone (GH) post-myocardial infarction, but its effect on arrhythmogenesis is unknown. Here, we assessed the medium-term electrophysiologic remodeling after intra-myocardial GH administration in (n = 33) rats. GH was released from an alginate scaffold, injected around the ischemic myocardium after coronary ligation. Two weeks thereafter, ventricular tachyarrhythmias were induced by programmed electrical stimulation. Monophasic action potentials were recorded from the infarct border, coupled with evaluation of electrical conduction and repolarization from a multi-electrode array. The arrhythmia score was lower in GH-treated rats than in alginate-treated rats or controls. The shape and the duration of the action potential at the infarct border were preserved, and repolarization-dispersion was attenuated after GH; moreover, voltage rise was higher and activation delay was shorter. GH normalized also right ventricular parameters. Intra-myocardial GH preserved electrical conduction and repolarization-dispersion at the infarct border and decreased the incidence of induced tachyarrhythmias in rats post-ligation. The long-term antiarrhythmic potential of GH merits further study.
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Affiliation(s)
- Marianthi Kontonika
- a Department of Cardiology , Medical School, University of Ioannina , Greece
- b Cardiovascular Research Institute , Ioannina , Greece
| | - Eleonora Barka
- b Cardiovascular Research Institute , Ioannina , Greece
- c Ceramics and Composites Laboratory, Department of Materials Science and Engineering , University of Ioannina , Ioannina , Greece
| | - Maria Roumpi
- b Cardiovascular Research Institute , Ioannina , Greece
- c Ceramics and Composites Laboratory, Department of Materials Science and Engineering , University of Ioannina , Ioannina , Greece
| | | | | | - Evangelos P Daskalopoulos
- b Cardiovascular Research Institute , Ioannina , Greece
- d Pole of Cardiovascular Research, Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique , Brussels , Belgium
| | | | | | - Antonios P Vlahos
- b Cardiovascular Research Institute , Ioannina , Greece
- e Pediatric Cardiology, Department of Child Health , Medical School, University of Ioannina , Ioannina , Greece
| | - Simeon Agathopoulos
- b Cardiovascular Research Institute , Ioannina , Greece
- c Ceramics and Composites Laboratory, Department of Materials Science and Engineering , University of Ioannina , Ioannina , Greece
| | - Theofilos M Kolettis
- a Department of Cardiology , Medical School, University of Ioannina , Greece
- b Cardiovascular Research Institute , Ioannina , Greece
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Early ventricular tachyarrhythmias after coronary artery bypass grafting surgery: Is it a real burden? J Cardiol 2017; 70:263-270. [PMID: 28069327 DOI: 10.1016/j.jjcc.2016.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 10/21/2016] [Accepted: 12/13/2016] [Indexed: 11/21/2022]
Abstract
BACKGROUND The prevalence of ventricular dysrhythmias (VD) [ventricular premature beats (VPBs), ventricular couplets (Vcouplets), ventricular runs (Vruns)] after coronary artery bypass grafting (CABG) has so far not been examined. The goal of this study is to examine characteristics of VD and whether they precede ventricular tachyarrhythmias (VTA) during a postoperative follow-up period of 5 days using continuous rhythm registrations. In addition, we determined predictive factors of VD/VTA. METHODS Incidences and burdens of VD/VTA were calculated in patients (N=105, 83 male, 65±9 years) undergoing primary, on-pump CABG. Independent risk factors were examined using multivariate analysis. RESULTS VPBs, Vcouplets, and Vruns occurred in respectively 100%, 82.9%, and 48.6% with corresponding burdens of 0.05%, 0%, and 0%. Sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) did not occur in our cohort. Independent risk factors for VD included male gender, mitral valve insufficiency, hyperlipidemia, and age ≥60 years. CONCLUSIONS VD are common in patients with coronary artery disease after CABG. Despite high incidences of these dysrhythmias, corresponding burdens are low and sustained VT or VF did not occur. Incidences were highest on the first postoperative day and diminished over time.
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Kolettis TM, Kontonika M, La Rocca V, Vlahos AP, Baltogiannis GG, Kyriakides ZS. Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin. J Arrhythm 2016; 33:144-146. [PMID: 28416983 PMCID: PMC5388042 DOI: 10.1016/j.joa.2016.07.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 06/23/2016] [Accepted: 07/19/2016] [Indexed: 01/01/2023] Open
Abstract
We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ETB-deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ETB-deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.
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Affiliation(s)
- Theofilos M Kolettis
- Cardiovascular Research Institute, 1 Stavrou Niarxou Ave., 45500 Ioannina, Greece
| | - Marianthi Kontonika
- Cardiovascular Research Institute, 1 Stavrou Niarxou Ave., 45500 Ioannina, Greece
| | - Vassilios La Rocca
- Cardiovascular Research Institute, 1 Stavrou Niarxou Ave., 45500 Ioannina, Greece
| | - Antonios P Vlahos
- Cardiovascular Research Institute, 1 Stavrou Niarxou Ave., 45500 Ioannina, Greece
| | | | - Zenon S Kyriakides
- Cardiovascular Research Institute, 1 Stavrou Niarxou Ave., 45500 Ioannina, Greece
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Effects of central sympathetic activation on repolarization-dispersion during short-term myocardial ischemia in anesthetized rats. Life Sci 2015; 144:170-7. [PMID: 26679103 DOI: 10.1016/j.lfs.2015.12.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Revised: 11/08/2015] [Accepted: 12/07/2015] [Indexed: 12/28/2022]
Abstract
AIMS Sympathetic activation during myocardial ischemia enhances arrhythmogenesis, but the underlying pathophysiologic mechanisms remain unclear. We investigated the central sympathetic effects on ventricular repolarization during the early-period post-coronary artery occlusion. MAIN METHODS We studied 12 Wistar rats (254±2 g) for 30 min following left coronary artery ligation, with (n=6) or without (n=6) pretreatment with the central sympatholytic agent clonidine. Mapping of left and right ventricular epicardial electrograms was performed with a 32-electrode array. As an index of sympathetic activation, heart rate variability in the frequency domain was calculated. Heart rate and repolarization duration were measured with a custom-made recording and analysis software, followed by calculation of intra- and inter-ventricular dispersion of repolarization. KEY FINDINGS Heart rate and heart rate variability indicated lower sympathetic activation in clonidine-treated rats during ischemia. Repolarization duration in the left ventricle prolonged after clonidine at baseline, independently of heart rate, but no differences were present 30 min post-ligation. Dispersion of repolarization in the right ventricle remained stable during ischemia, whereas it increased in the left ventricle, equally in both groups. A similar trend was observed for inter-ventricular dispersion, without differences between groups. SIGNIFICANCE In addition to intra-ventricular repolarization-dispersion, anterior-wall myocardial ischemia may also increase inter-ventricular repolarization-dispersion. Progressive central sympathetic activation occurs during myocardial ischemia, but it does not affect intra- or inter-ventricular dispersion of ventricular repolarization during the early phase. Further research is warranted on the potential effects during subsequent time-periods.
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Marcsa B, Dénes R, Vörös K, Rácz G, Sasvári-Székely M, Rónai Z, Törő K, Keszler G. A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease. PLoS One 2015; 10:e0132137. [PMID: 26146998 PMCID: PMC4492622 DOI: 10.1371/journal.pone.0132137] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Accepted: 06/10/2015] [Indexed: 11/18/2022] Open
Abstract
Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association.
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Affiliation(s)
- Boglárka Marcsa
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
| | - Réka Dénes
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
| | - Krisztina Vörös
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
| | - Gergely Rácz
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Mária Sasvári-Székely
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
| | - Zsolt Rónai
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
| | - Klára Törő
- Department of Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Gergely Keszler
- Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
- * E-mail:
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Kolettis TM, Kontonika M, Barka E, Daskalopoulos EP, Baltogiannis GG, Tourmousoglou C, Papalois A, Kyriakides ZS. Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors. Front Cardiovasc Med 2015; 2:6. [PMID: 26664878 PMCID: PMC4671362 DOI: 10.3389/fcvm.2015.00006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 02/10/2015] [Indexed: 12/15/2022] Open
Abstract
Sympathetic activation during acute myocardial infarction (MI) is an important arrhythmogenic mechanism, but the role of central autonomic inputs and their modulating factors remain unclear. Using the in vivo rat-model, we examined the effects of clonidine, a centrally acting sympatholytic agent, in the presence or absence of myocardial endothelin-B (ETB) receptors. We studied wild-type (n = 20) and ETB-deficient rats (n = 20) after permanent coronary ligation, with or without pretreatment with clonidine. Cardiac rhythm was continuously recorded for 24 h by implantable telemetry devices, coupled by the assessment of autonomic and heart failure indices. Sympathetic activation and arrhythmogenesis were more prominent in ETB-deficient rats during the early phase post-ligation. Clonidine improved these outcomes throughout the observation period in ETB-deficient rats, but only during the delayed phase in wild-type rats. However, this benefit was counterbalanced by atrioventricular conduction abnormalities and by higher incidence of heart failure, the latter particularly evident in ETB-deficient rats. Myocardial ETB-receptors attenuate the arrhythmogenic effects of central sympathetic activation during acute MI. ETB-receptor deficiency potentiates the sympatholytic effects of clonidine and aggravates heart failure. The interaction between endothelin and sympathetic responses during myocardial ischemia/infarction and its impact on arrhythmogenesis and left ventricular dysfunction merits further investigation.
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Affiliation(s)
| | | | - Eleonora Barka
- Cardiovascular Research Institute , Ioannina and Athens , Greece
| | | | | | | | - Apostolos Papalois
- Cardiovascular Research Institute , Ioannina and Athens , Greece ; Experimental Research Center ELPEN , Athens , Greece
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Kolettis TM, Kontonika M, Valenti MC, Vilaeti AD, Baltogiannis GG, Papalois A, Kyriakides ZS. Arrhythmogenesis after acute myocardial necrosis with and without preceding ischemia in rats. J Basic Clin Physiol Pharmacol 2014; 25:143-53. [PMID: 24114909 DOI: 10.1515/jbcpp-2013-0117] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 09/04/2013] [Indexed: 11/15/2022]
Abstract
BACKGROUND The relative role of acute myocardial ischemia and infarction in ventricular arrhythmogenesis is incompletely understood. We compared the arrhythmia pattern after ischemia/infarction to that observed after direct myocardial necrosis without preceding ischemia in rats. METHODS Coagulation necrosis was induced in Wistar rats (n=20, 280±3 g) by radiofrequency current application (for 15 s) from a 4-mm-tip ablation catheter. Myocardial infarction was induced by coronary artery ligation with (n=10) or without (n=10) reperfusion. Using 24-h telemetry recording, we examined ventricular arrhythmias, voluntary motor activity and indices of sympathetic activation. RESULTS The coagulation-necrosis volume was 24.4%±0.6%, comparable to the infarct size in the absence of reperfusion. Acute left ventricular failure and sympathetic activation were similar in the three groups. Coagulation necrosis induced ventricular fibrillation immediately, followed by a second peak after ∼1 h. Reperfusion decreased ventricular arrhythmias, whereas a second arrhythmogenic period (between the third and the eight hour) was noted in non-reperfused infarcts (mainly monomorphic ventricular tachycardia). CONCLUSIONS Distinct arrhythmia patterns occur after myocardial infarction (with or without reperfusion) and after direct necrosis. They are not produced by differences in sympathetic activation and are likely related to the evolution of myocardial injury. The necrosis rat model may be useful in studies of arrhythmogenesis.
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Ma Y, Wang Y, Gao Y, Fu Y, Li J. Total flavonoids from Ganshanbian (Herba Hyperici Attenuati) effect the expression of CaL-α1C and KATP-Kir6.1 mRNA of the myocardial cell membrane in myocardial ischemia-reperfusion arrhythmia rats. J TRADIT CHIN MED 2014; 34:357-61. [DOI: 10.1016/s0254-6272(14)60102-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Thomas CJ. Improving cardiac autonomic function following myocardial infarction: the case for anticholinesterase drugs. Clin Exp Pharmacol Physiol 2014; 40:597-9. [PMID: 23967803 DOI: 10.1111/1440-1681.12146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Kolettis TM, Oikonomidis DL, Baibaki MEE, Barka E, Kontonika M, Tsalikakis DG, Papalois A, Kyriakides ZS. Endothelin B-receptors and sympathetic activation: impact on ventricular arrhythmogenesis during acute myocardial infarction. Life Sci 2014; 118:281-7. [PMID: 24503339 DOI: 10.1016/j.lfs.2014.01.069] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/26/2013] [Accepted: 01/23/2014] [Indexed: 12/26/2022]
Abstract
AIMS We investigated the role of endothelin-B receptors on sympathetic activation originating from the adrenal gland or from the myocardium and its impact on arrhythmogenesis during acute myocardial infarction. MAIN METHODS We studied two groups of rats (n=120, 284±2 g), namely wild-type and ETB-deficient. Myocardial infarction was induced by permanent ligation of the left coronary artery and ventricular tachyarrhythmias were evaluated from continuous electrocardiographic recordings. Sympathetic activation, measured by indices of heart rate variability, was evaluated after adrenalectomy or catecholamine depletion induced by reserpine. Acute left ventricular failure was assessed by total animal activity. KEY FINDINGS Adrenalectomy decreased the total duration of tachyarrhythmias in ETB-deficient rats, but their incidence remained higher, compared to wild-type rats. After reserpine, heart rate variability indices and tachyarrhythmias were similar in the two groups during the initial, ischaemic phase. During evolving infarction, tachyarrhythmia duration was longer in ETB-deficient rats, despite lower sympathetic activation. Heart rate was lower in ETB-deficient rats throughout the 24-hour observation period, whereas activity was comparable in the two groups. SIGNIFICANCE Endothelin-B receptors modulate sympathetic activation during acute myocardial infarction not only in the ventricular myocardium, but also in the adrenal gland. Sympathetic activation markedly increases early-phase ventricular tachyarrhythmias, but other mechanisms involving the endothelin system underlie delayed arrhythmogenesis.
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Affiliation(s)
- Theofilos M Kolettis
- Department of Cardiology, University of Ioannina, Ioannina, Greece; Cardiovascular Research Institute, Ioannina and Athens, Greece.
| | | | - Maria-Eleni E Baibaki
- Department of Cardiology, University of Ioannina, Ioannina, Greece; Cardiovascular Research Institute, Ioannina and Athens, Greece; Experimental Research Center ELPEN, Pikermi, Athens, Greece
| | - Eleonora Barka
- Department of Materials Science and Engineering, University of Ioannina, Greece
| | - Marianthi Kontonika
- Department of Cardiology, University of Ioannina, Ioannina, Greece; Cardiovascular Research Institute, Ioannina and Athens, Greece
| | - Dimitrios G Tsalikakis
- Engineering Informatics and Telecommunications, University of Western Macedonia, Kozani, Greece
| | - Apostolos Papalois
- Cardiovascular Research Institute, Ioannina and Athens, Greece; Experimental Research Center ELPEN, Pikermi, Athens, Greece
| | - Zenon S Kyriakides
- Cardiovascular Research Institute, Ioannina and Athens, Greece; First Department of Cardiology, Red Cross Hospital, Athens, Greece
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Kolettis TM. Ventricular tachyarrhythmias during acute myocardial infarction: the role of endothelin-1. Life Sci 2014; 118:136-40. [PMID: 24486303 DOI: 10.1016/j.lfs.2014.01.060] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/23/2013] [Accepted: 01/13/2014] [Indexed: 11/16/2022]
Abstract
Ventricular arrhythmogenesis during acute coronary syndromes is a common cause of sudden cardiac death, but the underlying mechanisms remain incompletely understood. Recent evidence indicates an emerging pathophysiologic role of endothelin-1 during myocardial ischaemia and evolving infarction. At the early stages post-coronary occlusion, endothelin-1 enhances sympathetic activation, an effect mediated via the ETA receptor, whereas the ETB receptor exerts protective actions. The importance of this interaction is clearly decreased during subsequent stages, during which endothelin-1 may participate in the genesis of ventricular tachycardia or fibrillation via other mechanisms; of these, the effects of endothelin-1 on repolarizing potassium currents and electrical conduction via gap junctions merit further research. The relative roles of ETA and ETB receptors during this phase are unclear. Evaluation of the arrhythmogenic effects of endothelin-1 during acute coronary syndromes may provide the tools towards lowering sudden cardiac death rates.
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Affiliation(s)
- Theofilos M Kolettis
- Department of Cardiology, University of Ioannina, Cardiovascular Research Institute, Ioannina and Athens, Greece.
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Abstract
In 1913, exactly 100 years ago, Nikolai Nikolaevich Anichkov (1885-1964) and Semen Sergeevich Chalatov (1884-1951) discovered in St. Petersburg, Russia, that atherosclerosis of large arteries is critically dependent on cholesterol. The inflammatory nature of atherosclerosis was first observed and suggested by Rudolf Virchow in 1856. Today, we have orally active drugs at our disposition that not only lower cholesterol levels but also interfere with vascular inflammation and atherogenesis. The disease process is multifactorial and its development is accelerated by modifiable and given risk factors such as cigarette smoking, dyslipidemia, arterial hypertension, diabetes, obesity, physical inactivity, estrogen deficiency, chronic renal disease, genetic predisposition, and the physiological aging process, among others. The present issue of Current Opinion in Pharmacology features a collection of articles by clinicians and scientists-many of whom are world authorities in their field-on mechanisms, preventive measures, clinical complications, and treatment of coronary artery disease. This monograph provides a '2013 update' on the pathogenesis, prevention, and therapy of atherosclerosis.
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Kolettis TM, Vilaeti AD, Tsalikakis DG, Zoga A, Valenti M, Tzallas AT, Papalois A, Iliodromitis EK. Effects of Pre- and Postconditioning on Arrhythmogenesis in the In Vivo Rat Model. J Cardiovasc Pharmacol Ther 2013; 18:376-85. [DOI: 10.1177/1074248413482183] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The antiarrhythmic potential of postconditioning in in vivo models remains poorly defined. We compared the effects of pre- and postconditioning on ventricular arrhythmogenesis against controls with and without reperfusion. Wistar rats (n = 40, 269 ± 3 g) subjected to ischemia (30 minutes)–reperfusion (24 hours) were assigned to the following groups: (1) preconditioning (2 cycles), (2) postconditioning (6 cycles), or (3) no intervention and were compared with (4) nonreperfused infarcts and (5) sham-operated animals. Infarct size was measured, and arrhythmogenesis was evaluated with continuous telemetric electrocardiographic recording, heart rate variability indices, and monophasic action potentials (MAPs). During a 24-hour observation period, no differences in mortality were observed. Reperfusion decreased infarct size and ameliorated sympathetic activation during the late reperfusion phase. Preconditioning decreased infarct size by a further 35% ( P = .0017), but only a marginal decrease (by 18%, P = .075) was noted after postconditioning. Preconditioning decreased arrhythmias during ischemia and early reperfusion, whereas postconditioning almost abolished them during the entire reperfusion period. No differences were noted in MAPs or in the magnitude of sympathetic activation between the 2 interventions. Compared to postconditioning, preconditioning affords more powerful cytoprotection, but both interventions exert antiarrhythmic actions. In the latter, these are mainly evident during the ischemic phase and continue during early reperfusion. Postconditioning markedly decreases reperfusion arrhythmias during a prolonged observation period. The mechanisms underlying the antiarrhythmic effects of pre- and postconditioning are likely different but remain elusive.
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Affiliation(s)
- Theofilos M. Kolettis
- Medical School, University of Ioannina, Ioannina, Greece
- Cardiovascular Research Institute, Ioannina and Athens, Greece
| | - Agapi D. Vilaeti
- Cardiovascular Research Institute, Ioannina and Athens, Greece
- Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece
| | - Dimitrios G. Tsalikakis
- Department of Engineering Informatics and Telecommunications, Computational Cardiology and Modeling, University of Western Macedonia, Kozani, Greece
| | - Anastasia Zoga
- Second Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Mesele Valenti
- Cardiovascular Research Institute, Ioannina and Athens, Greece
| | - Alexandros T. Tzallas
- Department of Informatics & Telecommunications Technology, Technological Educational Institute of Epirus, Arta, Greece
| | - Apostolos Papalois
- Cardiovascular Research Institute, Ioannina and Athens, Greece
- ELPEN Research Laboratory, Pikermi, Athens, Greece
| | - Efstathios K. Iliodromitis
- Second Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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