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Li Z, Qin L, Xu X, Chen R, Zhang G, Wang B, Li B, Chu XM. Immune modulation: the key to combat SARS-CoV-2 induced myocardial injury. Front Immunol 2025; 16:1561946. [PMID: 40438117 PMCID: PMC12116346 DOI: 10.3389/fimmu.2025.1561946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/23/2025] [Indexed: 06/01/2025] Open
Abstract
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the Coronavirus disease 2019 (COVID-19) pandemic, has posed significant healthcare challenges. In addition to respiratory complications, it has led to severe damage in other organs, particularly the cardiovascular system. Of which, myocardial injury is increasingly recognized as a most significant complication, contributing to the high mortality. Recent research indicates the pivotal role of immune dysregulation in mediating myocardial injury in patients infected with SARS-CoV-2. In this review, we provide a comprehensive analysis of the immune mechanisms involved in SARS-CoV-2-induced myocardial damage, focusing on the roles of key immune cells and molecules that contribute to this pathological process. Aiming at mitigating the myocardial injury of COVID-19, we review immune-based treatments under evaluation in preclinical and clinical trials. Along with talking about the similarities and differences in myocardial injury resulting from SARS-CoV-2, the Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV). This article provides a unique perspective on using past experiences to prevent myocardial injury in the face of ongoing virus mutations.
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Affiliation(s)
- Zhaoqing Li
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Luning Qin
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xiaojian Xu
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ruolan Chen
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Guoliang Zhang
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Banghui Wang
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Bing Li
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xian-Ming Chu
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China
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Motairek I, Abdulhai F, Badwan O, Issa R, Calcagno T, Mirzai S, Tamis-Holland JE, Husni ME, Wassif HS. Sex Differences in Cardiovascular Mortality Among Patients With Immune Mediated Inflammatory Diseases. Circ Cardiovasc Qual Outcomes 2025; 18:e011833. [PMID: 40321135 DOI: 10.1161/circoutcomes.124.011833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Affiliation(s)
- Issam Motairek
- Department of Internal Medicine (I.M., F.A., R.I., T.C.), Cleveland Clinic, OH
| | - Farah Abdulhai
- Department of Internal Medicine (I.M., F.A., R.I., T.C.), Cleveland Clinic, OH
| | - Osamah Badwan
- Department of Cardiovascular Medicine (O.B., J.E.T.-H., H.W.), Cleveland Clinic, OH
| | - Rochell Issa
- Department of Internal Medicine (I.M., F.A., R.I., T.C.), Cleveland Clinic, OH
| | - Tess Calcagno
- Department of Internal Medicine (I.M., F.A., R.I., T.C.), Cleveland Clinic, OH
| | - Saeid Mirzai
- Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (S.M.)
| | | | | | - Heba S Wassif
- Department of Cardiovascular Medicine (O.B., J.E.T.-H., H.W.), Cleveland Clinic, OH
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Cyr S, Abdelaziz L, Minichiello A, Bouvier M, Djona O, Fiset C, Tadros R, Levesque S, Daval C, Lavigne V, Khairy P, Nattel S, Brouillette J. Impact of antidepressant and antipsychotic use in the occurence of torsades de pointes arrhythmia: a case-control study. Gen Hosp Psychiatry 2025; 94:16-23. [PMID: 39983427 DOI: 10.1016/j.genhosppsych.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 02/04/2025] [Accepted: 02/04/2025] [Indexed: 02/23/2025]
Abstract
OBJECTIVES AND METHODS Psychotropic drugs may prolong the corrected QT interval (QTc), which has been associated with torsades de pointes (TdP). Our aim is to measure the relative impact of psychotropic drug use on TdP. A case-control study was conducted on 110 cases of confirmed TdP, and 330 matched controls. Hierarchical regression was performed by first including pre-identified risk factors (including demographic, medical conditions, and drugs such as antiarrhythmics) and then psychotropic drugs (antidepressants and antipsychotics). Population attributable risks (PAR) were calculated. RESULTS At the time of admission, TdP was the primary, secondary, or complication diagnosis in 32.7 %, 30.9 %, and 36.4 % of cases, respectively. There were more patients with TdP who died during hospitalization compared to controls (7.3 % vs. 2.7 %, p < 0.05), but TdP was the cause of death in only two (1.8 %) of them. In our final regression model, age, hepatic and/or renal failure and antidepressant/antipsychotic drug monotherapy were not associated with TdP. On the other hand, the use of other QTc-prolonging drugs, female sex, left ventricular dysfunction, acute myocardial infarction, hypokalemia, and use of ≥ 2 antidepressants were all significantly associated with TdP, with PAR of 55.3 %, 41.8 %, 26.2 %, 13.0 %, 11.7 %, and 6.3 % respectively. CONCLUSIONS In analyses adjusting for concomitant conditions/drugs, antidepressant or antipsychotic monotherapy was not associated with TdP while the use of ≥ 2 antidepressants was. However in terms of PAR, the use of other QTc-prolonging drug, including antiarrhythmics, sex, and left ventricular dysfunction carried a higher burden than the use of ≥2 antidepressants. These findings may inform and assist in balancing the risks and benefits of psychotropic drugs.
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Affiliation(s)
- Samuel Cyr
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
| | - Lydia Abdelaziz
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Anthony Minichiello
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Maxime Bouvier
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Orielle Djona
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Céline Fiset
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
| | - Rafik Tadros
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Sylvie Levesque
- Montreal Health Innovations Coordinating Center, Montreal, Quebec, Canada
| | - Charline Daval
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Viviane Lavigne
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
| | - Paul Khairy
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
| | - Stanley Nattel
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada; Department of Pharmacology, McGill University, Montreal, Quebec, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany
| | - Judith Brouillette
- Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
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Bahrami P, Aromolaran KA, Aromolaran AS. Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction. Int J Mol Sci 2024; 25:13423. [PMID: 39769189 PMCID: PMC11677834 DOI: 10.3390/ijms252413423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/05/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is increasing at an alarming rate worldwide, with limited effective therapeutic interventions in patients. Sudden cardiac death (SCD) and ventricular arrhythmias present substantial risks for the prognosis of these patients. Obesity is a risk factor for HFpEF and life-threatening arrhythmias. Obesity and its associated metabolic dysregulation, leading to metabolic syndrome, are an epidemic that poses a significant public health problem. More than one-third of the world population is overweight or obese, leading to an enhanced risk of incidence and mortality due to cardiovascular disease (CVD). Obesity predisposes patients to atrial fibrillation and ventricular and supraventricular arrhythmias-conditions that are caused by dysfunction in the electrical activity of the heart. To date, current therapeutic options for the cardiomyopathy of obesity are limited, suggesting that there is considerable room for the development of therapeutic interventions with novel mechanisms of action that will help normalize sinus rhythms in obese patients. Emerging candidates for modulation by obesity are cardiac ion channels and Ca-handling proteins. However, the underlying molecular mechanisms of the impact of obesity on these channels and Ca-handling proteins remain incompletely understood. Obesity is marked by the accumulation of adipose tissue, which is associated with a variety of adverse adaptations, including dyslipidemia (or abnormal systemic levels of free fatty acids), increased secretion of proinflammatory cytokines, fibrosis, hyperglycemia, and insulin resistance, which cause electrical remodeling and, thus, predispose patients to arrhythmias. Furthermore, adipose tissue is also associated with the accumulation of subcutaneous and visceral fat, which is marked by distinct signaling mechanisms. Thus, there may also be functional differences in the effects of the regional distribution of fat deposits on ion channel/Ca-handling protein expression. Evaluating alterations in their functional expression in obesity will lead to progress in the knowledge of the mechanisms responsible for obesity-related arrhythmias. These advances are likely to reveal new targets for pharmacological modulation. Understanding how obesity and related mechanisms lead to cardiac electrical remodeling is likely to have a significant medical and economic impact. Nevertheless, substantial knowledge gaps remain regarding HFpEF treatment, requiring further investigations to identify potential therapeutic targets. The objective of this study is to review cardiac ion channel/Ca-handling protein remodeling in the predisposition to metabolic HFpEF and arrhythmias. This review further highlights interleukin-6 (IL-6) as a potential target, cardiac bridging integrator 1 (cBIN1) as a promising gene therapy agent, and leukotriene B4 (LTB4) as an underappreciated pathway in future HFpEF management.
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Affiliation(s)
- Pegah Bahrami
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, 95 S 2000 E, Salt Lake City, UT 84112, USA; (P.B.); (K.A.A.)
| | - Kelly A. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, 95 S 2000 E, Salt Lake City, UT 84112, USA; (P.B.); (K.A.A.)
| | - Ademuyiwa S. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, 95 S 2000 E, Salt Lake City, UT 84112, USA; (P.B.); (K.A.A.)
- Department of Surgery, Division of Cardiothoracic Surgery, Nutrition & Integrative Physiology, Biochemistry & Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Samat AHA, Cassar MP, Akhtar AM, McCracken C, Ashkir ZM, Mills R, Moss AJ, Finnigan LEM, Lewandowski AJ, Mahmod M, Ogbole GI, Tunnicliffe EM, Lukaschuk E, Piechnik SK, Ferreira VM, Nikolaidou C, Rahman NM, Ho LP, Harris VC, Singapuri A, Manisty C, O'Regan DP, Weir-McCall JR, Steeds RP, Llm KP, Cuthbertson DJ, Kemp GJ, Horsley A, Miller CA, O'Brien C, Chiribiri A, Francis ST, Chalmers JD, Plein S, Poener AM, Wild JM, Treibel TA, Marks M, Toshner M, Wain LV, Evans RA, Brightling CE, Neubauer S, McCann GP, Raman B. Diagnostic utility of electrocardiogram for screening of cardiac injury on cardiac magnetic resonance in post-hospitalised COVID-19 patients: a prospective multicenter study. Int J Cardiol 2024; 415:132415. [PMID: 39127146 DOI: 10.1016/j.ijcard.2024.132415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 07/03/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND The role of ECG in ruling out myocardial complications on cardiac magnetic resonance (CMR) is unclear. We examined the clinical utility of ECG in screening for cardiac abnormalities on CMR among post-hospitalised COVID-19 patients. METHODS Post-hospitalised patients (n = 212) and age, sex and comorbidity-matched controls (n = 38) underwent CMR and 12‑lead ECG in a prospective multicenter follow-up study. Participants were screened for routinely reported ECG abnormalities, including arrhythmia, conduction and R wave abnormalities and ST-T changes (excluding repolarisation intervals). Quantitative repolarisation analyses included corrected QT (QTc), corrected QT dispersion (QTc disp), corrected JT (JTc) and corrected T peak-end (cTPe) intervals. RESULTS At a median of 5.6 months, patients had a higher burden of ECG abnormalities (72.2% vs controls 42.1%, p = 0.001) and lower LVEF but a comparable cumulative burden of CMR abnormalities than controls. Patients with CMR abnormalities had more ECG abnormalities and longer repolarisation intervals than those with normal CMR and controls (82% vs 69% vs 42%, p < 0.001). Routinely reported ECG abnormalities had poor discriminative ability (area-under-the-receiver-operating curve: AUROC) for abnormal CMR, AUROC 0.56 (95% CI 0.47-0.65), p = 0.185; worse among female than male patients. Adding JTc and QTc disp improved the AUROC to 0.64 (95% CI 0.55-0.74), p = 0.002, the sensitivity of the ECG increased from 81.6% to 98.0%, negative predictive value from 84.7% to 96.3%, negative likelihood ratio from 0.60 to 0.13, and reduced sex-dependence variabilities of ECG diagnostic parameters. CONCLUSION Post-hospitalised COVID-19 patients have more ECG abnormalities than controls. Normal ECGs, including normal repolarisation intervals, reliably exclude CMR abnormalities in male and female patients.
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Affiliation(s)
- Azlan Helmy Abd Samat
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK; Department of Emergency Medicine, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Mark P Cassar
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Abid M Akhtar
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | | | - Zakariye M Ashkir
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Rebecca Mills
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Alastair J Moss
- University Hospitals of Leicester NHS Trust & University of Leicester, Leicester, UK
| | | | - Adam J Lewandowski
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Masliza Mahmod
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Godwin I Ogbole
- University of Oxford, Oxford, UK; Department of Radiology, University of Ibadan, Nigeria
| | | | | | | | - Vanessa M Ferreira
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | | | - Najib M Rahman
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Center, Oxford, UK; Oxford Chinese Academy of Medicine Institute, Oxford, UK
| | - Ling-Pei Ho
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Victoria C Harris
- University Hospitals of Leicester NHS Trust & University of Leicester, Leicester, UK
| | - Amisha Singapuri
- University Hospitals of Leicester NHS Trust & University of Leicester, Leicester, UK
| | | | - Declan P O'Regan
- MRC London Institute of Medical Sciences, Imperial College London, UK
| | - Jonathan R Weir-McCall
- Royal Papworth Hospital, Cambridge, UK; Cambridge NIHR BRC and the NIHR Cambridge Clinical Research Facility, Cambridge, UK
| | - Richard P Steeds
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Dan J Cuthbertson
- University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Graham J Kemp
- University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Alexander Horsley
- Manchester University NHS Foundation Trust & University of Manchester, Manchester, UK
| | - Christopher A Miller
- Manchester University NHS Foundation Trust & University of Manchester, Manchester, UK
| | - Caitlin O'Brien
- King's College London, Guy's & St Thomas' NHS Foundation Trust, London, UK
| | - Amedeo Chiribiri
- King's College London, Guy's & St Thomas' NHS Foundation Trust, London, UK
| | | | | | - Sven Plein
- University of Leeds & Leeds Teaching Hospitals, Leeds, UK
| | | | - James M Wild
- Sheffield Teaching Hospitals, University of Sheffield, Leicester, UK
| | | | - Michael Marks
- University College London NHS Foundation Trust, London, UK; London School of Hygiene & Tropical Medicine, London, UK
| | - Mark Toshner
- Heart and Lung Research Institute, Dept of Medicine, Cambridge, UK; Cambridge NIHR BRC and the NIHR Cambridge Clinical Research Facility, Cambridge, UK
| | - Louise V Wain
- Department of Population Health Sciences, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Center, Leicester, UK
| | - Rachael A Evans
- University Hospitals of Leicester NHS Trust & University of Leicester, Leicester, UK
| | | | - Stefan Neubauer
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK
| | - Gerry P McCann
- University Hospitals of Leicester NHS Trust & University of Leicester, Leicester, UK
| | - Betty Raman
- Oxford University Hospitals NHS Foundation Trust & University of Oxford, Oxford, UK.
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Spinelli V, Laurino A, Balducci V, Gencarelli M, Ruzzolini J, Nediani C, Mandoli GE, Cameli M, Sacconi L, Sartiani L, Cerbai E. Interleukin-6 Modulates the Expression and Function of HCN Channels: A Link Between Inflammation and Atrial Electrogenesis. Int J Mol Sci 2024; 25:12212. [PMID: 39596280 PMCID: PMC11594737 DOI: 10.3390/ijms252212212] [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: 10/15/2024] [Revised: 11/04/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Inflammatory cytokines, including interleukin 6 (IL6), are associated with ion channel remodeling and enhance the propensity to alterations in cardiac rhythm generation and propagation, in which the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role. Hence, we investigated the consequences of exposure to IL6 on HCN channels in cell models and human atrial biopsies. In murine atrial HL1 cells and in cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs), IL6 elicited STAT3 phosphorylation, a receptor-mediated downstream signaling. Downregulation of HCN1,2,4 by IL6 was observed after 24-48 h; in hiPS-CMs, this effect was reverted by 24 h of application of tocilizumab, a human IL6 receptor antagonist. In parallel, hiPS-CM action potentials (APs) showed a reduced spontaneous frequency. Moreover, we assessed IL6 and HCN expression in dilated left atrial samples from patients with mitral valve disease, an AF-prone condition. IL6 levels were increased in dilated atria compared to controls and positively correlated with echocardiographic atrial dimensions. Interestingly, the highest IL6 transcript levels and the lowest HCN4 and HCN2 expression were in these samples. In conclusion, our data uncovered a novel link between IL6 and cardiac HCN channels, potentially contributing to atrial electrical disturbances and a higher risk of dysrhythmias in conditions with elevated IL6 levels.
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Affiliation(s)
- Valentina Spinelli
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
| | - Annunziatina Laurino
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
- Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
| | - Valentina Balducci
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
| | - Manuela Gencarelli
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
- Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, NY 10024, USA
| | - Jessica Ruzzolini
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
| | - Chiara Nediani
- Department of Experimental and Clinical Biomedical Sciences, University of Firenze, 50139 Firenze, Italy;
| | - Giulia Elena Mandoli
- Department of Medical Biotechnologies, Division of Cardiology, University of Siena, 53100 Siena, Italy; (G.E.M.); (M.C.)
| | - Matteo Cameli
- Department of Medical Biotechnologies, Division of Cardiology, University of Siena, 53100 Siena, Italy; (G.E.M.); (M.C.)
| | - Leonardo Sacconi
- Institute of Clinical Physiology, National Research Council, 50139 Florence, Italy;
- Institute for Experimental Cardiovascular Medicine, University Heart Center and Medical Faculty, 79110 Freiburg, Germany
| | - Laura Sartiani
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
| | - Elisabetta Cerbai
- Department of Neuroscience, Innovative Treatment, Drug Research and Child Health, University of Firenze, 50139 Firenze, Italy; (V.S.); (A.L.); (V.B.); (M.G.); (J.R.)
- European Laboratory for Non-Linear Spectroscopy-LENS, Sesto Fiorentino, 50019 Firenze, Italy
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Ho CN, Chung WC, Kao CL, Hsu CW, Hung KC, Yu CH, Chen JY, Chen IW. Impact of preoperative QTc interval prolongation on short-term postoperative outcomes: A retrospective study. J Clin Anesth 2024; 98:111574. [PMID: 39121785 DOI: 10.1016/j.jclinane.2024.111574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/29/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024]
Abstract
STUDY OBJECTIVE Although a prolonged heart rate-corrected QT interval (QTcI) is associated with an increased risk of mortality in the general population, its prognostic value in surgical patients remains unclear. We aimed to examine whether preoperative QTcI prolongation predicts short-term postoperative outcomes in elderly patients undergoing noncardiac surgery. DESIGN The study was a retrospective analysis using the TriNetX network database. SETTING Operating room. INTERVENTION Assessment and categorization of preoperative QTcI. PATIENTS Data of patients aged ≥65 years who underwent non-cardiac surgery between 2010 and 2023 were analyzed. MEASUREMENTS Patients were categorized into four groups based on preoperative QTcI: long (500-600 ms), borderline (460-500 ms), high-normal (420-460 ms) and control (370-420 ms) groups. The groups were compared using a propensity score-matched analysis. The primary outcome was the all-cause 90-day mortality risk. The secondary outcomes included 90-day risks of postoperative new-onset atrial fibrillation (Af), ventricular arrhythmias (VAs), emergency visits, hospital readmissions, and pneumonia. RESULTS In total, data on 519,929 patients were collected in this study. Pairwise comparisons showed that all QTcI prolongation groups demonstrated a heightened incidence of postoperative mortality, arrhythmias, and other complications compared to the control group. Patients with a long QTcI had a 3-fold higher risk of mortality (hazard ratio [HR] = 3.124, p < 0.001), Af (HR = 3.059, p < 0.001), and VAs (HR = 3.617, p < 0.001) than controls. The risks of emergency visits (HR = 1.287, p < 0.001), hospital readmissions (HR = 1.591, p < 0.001), and pneumonia (HR = 1.672, p < 0.001) were also higher in the long QTcI group than in the control group. A dose-dependent response was evident between QTcI and mortality as well as arrhythmia risk. CONCLUSION Preoperative QTcI screening effectively risk-stratifies elderly surgical patients, with a QTcI≥500 ms being strongly predictive of short-term postoperative mortality and other complications. Incorporating QTcI assessment into the preoperative evaluation may guide perioperative monitoring and management.
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Affiliation(s)
- Chun-Ning Ho
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan; Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan
| | - Wei-Chu Chung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan
| | - Chia-Li Kao
- Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City 83301, Taiwan
| | - Kuo-Chuan Hung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan
| | - Chia-Hung Yu
- Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan
| | - Jen-Yin Chen
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan; Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan
| | - I-Wen Chen
- Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan City, Taiwan.
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8
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Ding E, Deng F, Fang J, Liu J, Yan W, Yao Q, Miao K, Wang Y, Sun P, Li C, Liu Y, Dong H, Dong L, Zhang X, Lu Y, Lin X, Ding C, Li T, Shi Y, Cai Y, Liu X, Godri Pollitt KJ, Ji JS, Tong S, Tang S, Shi X. Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study. ENVIRONMENTAL HEALTH PERSPECTIVES 2024; 132:97005. [PMID: 39240788 PMCID: PMC11379127 DOI: 10.1289/ehp13864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/08/2024]
Abstract
BACKGROUND Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency > 50 % and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.
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Affiliation(s)
- Enmin Ding
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Fuchang Deng
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Jianlong Fang
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Juan Liu
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Wenyan Yan
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qiao Yao
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Ke Miao
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Yu Wang
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Peijie Sun
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Chenfeng Li
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Yuanyuan Liu
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Haoran Dong
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Li Dong
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Xu Zhang
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Yifu Lu
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Xiao Lin
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Changming Ding
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
| | - Tiantian Li
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yali Shi
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
| | - Yaqi Cai
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
| | - Xiaohui Liu
- National Protein Science Technology Center, Tsinghua University, Beijing, China
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Krystal J Godri Pollitt
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
| | - John S Ji
- Vanke School of Public Health, Tsinghua University, Beijing, China
| | - Shilu Tong
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
- School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, China
- School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia
| | - Song Tang
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiaoming Shi
- China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NIEH, China CDC, Beijing, China
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9
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Aromolaran KA, Corbin A, Aromolaran AS. Obesity Arrhythmias: Role of IL-6 Trans-Signaling. Int J Mol Sci 2024; 25:8407. [PMID: 39125976 PMCID: PMC11313575 DOI: 10.3390/ijms25158407] [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: 07/07/2024] [Revised: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6's pro-inflammatory effects are mediated via trans-signaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL-6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs.
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Affiliation(s)
- Kelly A. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84112, USA; (K.A.A.); (A.C.)
| | - Andrea Corbin
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84112, USA; (K.A.A.); (A.C.)
- Department of Biomedical Engineering, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
| | - Ademuyiwa S. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84112, USA; (K.A.A.); (A.C.)
- Department of Biomedical Engineering, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
- Department of Surgery, Division of Cardiothoracic Surgery, Nutrition & Integrative Physiology, Biochemistry & Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
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10
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Zhu W, Bian X, Lv J. From genes to clinical management: A comprehensive review of long QT syndrome pathogenesis and treatment. Heart Rhythm O2 2024; 5:573-586. [PMID: 39263612 PMCID: PMC11385408 DOI: 10.1016/j.hroo.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2024] Open
Abstract
Background Long QT syndrome (LQTS) is a rare cardiac disorder characterized by prolonged ventricular repolarization and increased risk of ventricular arrhythmias. This review summarizes current knowledge of LQTS pathogenesis and treatment strategies. Objectives The purpose of this study was to provide an in-depth understanding of LQTS genetic and molecular mechanisms, discuss clinical presentation and diagnosis, evaluate treatment options, and highlight future research directions. Methods A systematic search of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to April 2024. Results LQTS involves mutations in ion channel-related genes encoding cardiac ion channels, regulatory proteins, and other associated factors, leading to altered cellular electrophysiology. Acquired causes can also contribute. Diagnosis relies on clinical history, electrocardiographic findings, and genetic testing. Treatment strategies include lifestyle modifications, β-blockers, potassium channel openers, device therapy, and surgical interventions. Conclusion Advances in understanding LQTS have improved diagnosis and personalized treatment approaches. Challenges remain in risk stratification and management of certain patient subgroups. Future research should focus on developing novel pharmacological agents, refining device technologies, and conducting large-scale clinical trials. Increased awareness and education are crucial for early detection and appropriate management of LQTS.
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Affiliation(s)
- Wenjing Zhu
- Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xueyan Bian
- Department of Pediatrics, Lixia District People's Hospital, Jinan, Shandong, China
| | - Jianli Lv
- Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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11
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Corbin A, Aromolaran KA, Aromolaran AS. STAT4 Mediates IL-6 Trans-Signaling Arrhythmias in High Fat Diet Guinea Pig Heart. Int J Mol Sci 2024; 25:7813. [PMID: 39063055 PMCID: PMC11277091 DOI: 10.3390/ijms25147813] [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: 07/02/2024] [Revised: 07/15/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD)-induced arrhythmias that exhibit a heightened proinflammatory-like pathology, which is also observed in human obesity arrhythmias, as well as immunofluorescence and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling would exhibit increased ventricular arrhythmia/SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat diet (LFD)-fed controls, HFD promoted phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4), leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 compared to LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval, which resulted in greater susceptibility to arrhythmias/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective arrhythmia therapy in the vulnerable obese patient population.
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Affiliation(s)
- Andrea Corbin
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84132, USA; (A.C.); (K.A.A.)
- Department of Biomedical Engineering, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
| | - Kelly A. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84132, USA; (A.C.); (K.A.A.)
| | - Ademuyiwa S. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT 84132, USA; (A.C.); (K.A.A.)
- Department of Biomedical Engineering, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
- Department of Surgery, Division of Cardiothoracic Surgery, Nutrition & Integrative Physiology, Biochemistry & Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
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12
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Centner AM, Shiel EA, Farra W, Cannon EN, Landim-Vieira M, Salazar G, Chelko SP. High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy. Nutrients 2024; 16:2087. [PMID: 38999835 PMCID: PMC11243382 DOI: 10.3390/nu16132087] [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: 06/10/2024] [Revised: 06/25/2024] [Accepted: 06/26/2024] [Indexed: 07/14/2024] Open
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.
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Affiliation(s)
- Ann M Centner
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
| | - Emily A Shiel
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
| | - Waleed Farra
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
| | - Elisa N Cannon
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
| | - Maicon Landim-Vieira
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
| | - Gloria Salazar
- Department of Health, Nutrition, and Food Sciences, College of Education, Health, and Human Science, Florida State University, Center for Advancing Exercise and Nutrition Research on Aging (CAENRA), Tallahassee, FL 32306, USA
| | - Stephen P Chelko
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA
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13
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Dziadosz D, Daniłowicz-Szymanowicz L, Wejner-Mik P, Budnik M, Brzezińska B, Duchnowski P, Golińska-Grzybała K, Jaworski K, Jedliński I, Kamela M, Kasprzak J, Kowalczyk-Domagała M, Kurnicka K, Kustrzycka-Kratochwil D, Mickiewicz K, Możeńska O, Oko-Sarnowska Z, Plewka M, Polewczyk A, Uziębło-Życzkowska B, Wierzbowska-Drabik K, Wachnicka-Truty R, Wołoszyn-Horák E, Szymański P, Gackowski A, Mizia-Stec K. What Do We Know So Far About Ventricular Arrhythmias and Sudden Cardiac Death Prediction in the Mitral Valve Prolapse Population? Could Biomarkers Help Us Predict Their Occurrence? Curr Cardiol Rep 2024; 26:245-268. [PMID: 38507154 PMCID: PMC11136782 DOI: 10.1007/s11886-024-02030-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/22/2024] [Indexed: 03/22/2024]
Abstract
PURPOSE OF THE REVIEW To summarize currently available data on the topic of mitral valve prolapse (MVP) and its correlation to the occurrence of atrial and ventricular arrhythmias. To assess the prognostic value of several diagnostic methods such as transthoracic echocardiography, transesophageal echocardiography, cardiac magnetic resonance, cardiac computed tomography, electrocardiography, and electrophysiology concerning arrhythmic episodes. To explore intra and extracellular biochemistry of the cardiovascular system and its biomarkers as diagnostic tools to predict rhythm disturbances in the MVP population. RECENT FINDINGS MVP is a common and mainly benign valvular disorder. It affects 2-3% of the general population. MVP is a heterogeneous and highly variable phenomenon with three structural phenotypes: myxomatous degeneration, fibroelastic deficiency, and forme fruste. Exercise intolerance, supraventricular tachycardia, and chest discomfort are the symptoms that are often paired with psychosomatic components. Though MVP is thought to be benign, the association between isolated MVP without mitral regurgitation (MR) or left ventricle dysfunction, with ventricular arrhythmia (VA) and sudden cardiac death (SCD) has been observed. The incidence of SCD in the MVP population is around 0.6% per year, which is 6 times higher than the occurrence of SCD in the general population. Often asymptomatic MVP population poses a challenge to screen for VA and prevent SCD. Therefore, it is crucial to carefully assess the risk of VA and SCD in patients with MVP with the use of various tools such as diagnostic imaging and biochemical and genetic screening.
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Affiliation(s)
- D Dziadosz
- 1st Department of Cardiology, Faculty of Medicine, Medical University of Silesia, Katowice, Poland
- Centre of European Reference Network of Heart Diseases - ERN GUARD-HEART, 47 Ziołowa St, 40-635, Katowice, Poland
| | - L Daniłowicz-Szymanowicz
- Department of Cardiology and Electrotherapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - P Wejner-Mik
- 1st Department of Cardiology, Medical University of Lodz, Bieganski Hospital, Łódź, Poland
| | - M Budnik
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Central Clinical Hospital, 1a Banacha St, 02-97, Warsaw, Poland
| | - B Brzezińska
- Department of Cardiology, T. Marciniak Hospital, Wrocław, Poland
| | - P Duchnowski
- Cardinal Wyszynski National Institute of Cardiology, 04-628, Warsaw, Poland
| | - K Golińska-Grzybała
- Dept of Coronary Disease and Heart Failure, Noninvasive Cardiovascular Laboratory, Medical College, Jagiellonian University, St. John Paul II Hospital, Cracow, Poland
| | - K Jaworski
- Department of Coronary Artery Disease and Cardiac Rehabilitation, National Institute of Cardiology, Warsaw, Poland
| | - I Jedliński
- Medicor, Powstańców Wielkopolskich 4, 61-895, Poznań, Poland
| | - M Kamela
- Department of Cardiology, Hospital of the Ministry of Interior and Administration, Rzeszów, Poland
| | - J Kasprzak
- 1st Department of Cardiology, Medical University of Lodz, Bieganski Hospital, Łódź, Poland
| | - M Kowalczyk-Domagała
- Pediatric Cardiology Department, The Children's Memorial Health Institute, Warsaw, Poland
| | - K Kurnicka
- Department of Internal Medicine and Cardiology, Medical University of Warsaw, Infant Jesus Clinical Hospital, Lindleya str. 4, 02-005, Warsaw, Poland
| | - D Kustrzycka-Kratochwil
- Department of Cardiology, Center for Heart Diseases, 4th Military Clinical Hospital, Weigla 5, 50-981, Wrocław, Poland
| | - K Mickiewicz
- Department of Cardiology, Medical University of Bialystok, 15-276, Białystok, Poland
| | - O Możeńska
- JO Medical Center, Quo Vadis 1/U6, 02-495, Warsaw, Poland
| | - Z Oko-Sarnowska
- Department of Cardiology, Poznań University of Medical Sciences, Wielkopolskie, 60-355, Poznań, Poland
| | - M Plewka
- Department of Interventional Cardiology and Cardiac Arrhythmias, Military Medical Academy Memorial Teaching Hospital of the Medical University of Lodz, Łódź, Poland
| | - A Polewczyk
- Department of Physiology, Pathophysiology and Clinical Immunology, Institute of Medical Sciences, Jan Kochanowski University, Żeromskiego 5, 25-369, Kielce, Poland
- Department of Cardiac Surgery, Świętokrzyskie Cardiology Center, Grunwaldzka 45, 25-736, Kielce, Poland
| | - B Uziębło-Życzkowska
- Department of Cardiology and Internal Diseases, Military Institute of Medicine - National Research Institute, Warsaw, Poland
| | - K Wierzbowska-Drabik
- Department of Internal Medicine and Clinical Pharmacology, Medical University of Lodz, Łódź, Poland
| | - R Wachnicka-Truty
- Department of Cardiology and Internal Diseases, Institute of Maritime and Tropical Medicine, Medical University of Gdańsk, Gdynia, Poland
| | - E Wołoszyn-Horák
- Second Department of Cardiology. Specialist Hospital in Zabrze, Medical University of Silesia, Curie-Sklodowskiej str. 10, Zabrze, Poland
| | - P Szymański
- Center of Clinical Cardiology, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland
| | - A Gackowski
- Dept of Coronary Disease and Heart Failure, Noninvasive Cardiovascular Laboratory, Medical College, Jagiellonian University, St. John Paul II Hospital, Cracow, Poland
| | - K Mizia-Stec
- 1st Department of Cardiology, Faculty of Medicine, Medical University of Silesia, Katowice, Poland.
- Centre of European Reference Network of Heart Diseases - ERN GUARD-HEART, 47 Ziołowa St, 40-635, Katowice, Poland.
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14
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Lazzerini PE, Cupelli M, Cartocci A, Bertolozzi I, Salvini V, Accioli R, Salvadori F, Marzotti T, Verrengia D, Cevenini G, Bisogno S, Bicchi M, Donati G, Bernardini S, Laghi‐Pasini F, Acampa M, Capecchi PL, El‐Sherif N, Boutjdir M. Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans. J Am Heart Assoc 2024; 13:e032071. [PMID: 38348789 PMCID: PMC11010073 DOI: 10.1161/jaha.123.032071] [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: 08/03/2023] [Accepted: 12/13/2023] [Indexed: 02/21/2024]
Abstract
BACKGROUND Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects. METHODS AND RESULTS An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction. CONCLUSIONS Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.
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Affiliation(s)
| | - Michael Cupelli
- VA New York Harbor Healthcare SystemNew YorkNYUSA
- SUNY Downstate Health Sciences UniversityNew YorkNYUSA
| | | | - Iacopo Bertolozzi
- Cardiology Intensive Therapy Unit, Department of Internal MedicineNuovo Ospedale San Giovanni di Dio (former Cardiology Intensive Therapy Unit, Department of Internal Medicine, Hospital of Carrara, Carrara, Italy)FlorenceItaly
| | - Viola Salvini
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Riccardo Accioli
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Fabio Salvadori
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Tommaso Marzotti
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Decoroso Verrengia
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | | | - Stefania Bisogno
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Maurizio Bicchi
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Giovanni Donati
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Sciaila Bernardini
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Franco Laghi‐Pasini
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | - Maurizio Acampa
- Department of Medical Sciences, Surgery and NeurosciencesUniversity of SienaItaly
| | | | - Nabil El‐Sherif
- VA New York Harbor Healthcare SystemNew YorkNYUSA
- SUNY Downstate Health Sciences UniversityNew YorkNYUSA
| | - Mohamed Boutjdir
- VA New York Harbor Healthcare SystemNew YorkNYUSA
- SUNY Downstate Health Sciences UniversityNew YorkNYUSA
- NYU Grossman School of MedicineNew YorkNYUSA
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15
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Ilkhanoff L, Qian X, Lima JA, Tran H, Soliman EZ, Yeboah J, Seliger S, deFilippi CR. Electrocardiographic Associations of Cardiac Biomarkers and Cardiac Magnetic Resonance Measures of Fibrosis in the Multiethnic Study of Atherosclerosis (MESA). Am J Cardiol 2023; 204:287-294. [PMID: 37567020 DOI: 10.1016/j.amjcard.2023.07.041] [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: 01/30/2023] [Revised: 06/29/2023] [Accepted: 07/06/2023] [Indexed: 08/13/2023]
Abstract
Abnormalities in myocardial substrate, including diffuse and replacement fibrosis, increase the risk of cardiovascular disease (CVD). Data are sparse on whether electrocardiogram (ECG) measures, coupled with circulating biomarkers, may aid in identifying cardiac fibrosis. This study aimed to determine whether 12-lead ECG and biomarkers together augment the prediction of cardiac fibrosis in participants who are free of known CVD. This is a cross-sectional analysis in the MESA (Multiethnic Study of Atherosclerosis) study at visit 5 (2010 to 2012), with measurements of biomarkers (cardiac troponin T and growth differentiation factor-15), gadolinium-enhanced cardiac magnetic resonance imaging, and ECG. Logistic regression associations of ECG measures with cardiac magnetic resonance surrogates of fibrosis (highest quartile extracellular volume [interstitial fibrosis] and late gadolinium enhancement [replacement fibrosis]) were adjusted for demographics and risk factors. Using the C-statistic, we evaluated whether adding ECG measures and biomarkers to clinical characteristics improved the prediction of either type of fibrosis. There were 1,170 eligible participants (aged 67.1 ± 8.6 years). Among the ECG measures, QRS duration (odds ratio [OR] 1.41 per 10 ms, 95% confidence interval [CI] 1.10 to 1.81), major ST-T abnormalities (OR 3.03, 95%CI 1.20, 7.65), and abnormal QRS-T angle (OR 6.32, 95%CI 3.00, 13.33) were associated with replacement fibrosis, whereas only abnormal QRS-T angle (OR 3.05, 95%CI,1.69, 5.48) was associated with interstitial fibrosis. ECG markers, in addition to clinical characteristics, improved the prediction of replacement fibrosis (p = 0.002) but not interstitial fibrosis. The addition of cardiac troponin T and growth differentiation factor-15 to the ECG findings did not significantly improve the model discrimination for either type of cardiac fibrosis. In CVD free participants, simple ECG measures are associated with replacement fibrosis and interstitial fibrosis. The addition of these measures improves identification of replacement but not interstitial fibrosis. These findings may help refine the identification of myocardial scar in the general population.
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Affiliation(s)
| | - Xiaoxiao Qian
- Inova Heart and Vascular Institute, Fall Church, Virginia
| | - Joao A Lima
- Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Henry Tran
- Inova Heart and Vascular Institute, Fall Church, Virginia
| | | | - Joseph Yeboah
- Wake Forest University, Winston-Salem, North Carolina
| | - Stephen Seliger
- University of Maryland School of Medicine, Baltimore, Maryland
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16
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Shantha G, Brock J, Singleton MJ, Schmitt AJ, Kozak P, Bodziock G, Bradford N, Whalen P, Bhave P. A comparative study of the two leadless pacemakers in clinical practice. J Cardiovasc Electrophysiol 2023; 34:1896-1903. [PMID: 37522245 DOI: 10.1111/jce.16019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/01/2023] [Accepted: 07/13/2023] [Indexed: 08/01/2023]
Abstract
INTRODUCTION AVEIR-VR leadless pacemaker (LP) was recently approved for clinical use. Although trial data were promising, post-approval real world data with regard to its effectiveness and safety is lacking. To report our early experience with AVEIR-VR LP with regard to its effectiveness and safety and compare it with MICRA-VR. METHODS The first 25 patients to undergo AVEIR-VR implant at our institution between June and November 2022, were compared to 25 age- and sex-matched patients who received MICRA-VR implants. RESULTS In both groups, mean age was 73 years and 48% were women. LP implant was successful in 100% of patients in both groups. Single attempt deployment was achieved in 80% of AVEIR-VR and 60% of MICRA-VR recipients (p = 0.07). Fluoroscopy, implant, and procedure times were numerically longer in the AVEIR-VR group compared to MICRA-VR group (p > 0.05). No significant periprocedural complications were noted in both groups. Incidence of ventricular arrhythmias were higher in the AVEIR-VR group (20%) compared to the MICRA-VR group (0%) (p = 0.043). At 2 and 8 weeks follow-up, device parameters remained stable in both groups with no device dislodgements. The estimated battery life at 8 weeks was significantly longer in the AVEIR-VR group (15 years) compared to the MICRA-VR group (8 years) (p = 0.047). With 3-4 AVEIR-VR implants, the learning curve for successful implantation reached a steady state. CONCLUSION Our initial experience with AVEIR-VR show that it has comparable effectiveness and safety to MICRA-VR. Larger sample studies are needed to confirm our findings.
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Affiliation(s)
- Ghanshyam Shantha
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Jonathan Brock
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | | | | | - Patrick Kozak
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - George Bodziock
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Natalie Bradford
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Patrick Whalen
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Prashant Bhave
- Cardiac Electrophysiology, Wake Forest University, Winston-Salem, North Carolina, USA
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17
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Chang YT, Tzeng IS, Jang SJ, Liu KL, Hsieh CA, Chou HH, Yeh KH, Huang HL, TRENDPAD Study Group. Association between corrected QT interval and long-term cardiovascular outcomes in elderly patients who had undergone endovascular therapy for lower extremity arterial disease. Front Cardiovasc Med 2023; 10:1103520. [PMID: 37252112 PMCID: PMC10213350 DOI: 10.3389/fcvm.2023.1103520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 03/23/2023] [Indexed: 05/31/2023] Open
Abstract
BACKGROUND Population-based studies have reported the association between prolonged corrected QT (QTc) intervals and an increased risk of adverse cardiovascular events. Data regarding the association between longer QTc intervals and incident cardiovascular outcomes in patients with lower extremity arterial disease (LEAD) are scarce. OBJECTIVE To examine the impact of QTc interval on long-term cardiovascular outcomes in elderly patients with symptomatic LEAD. METHODS This cohort study extracted data from the Tzu-chi Registry of ENDovascular Intervention for Peripheral Artery Disease (TRENDPAD) and enrolled 504 patients aged ≥ 70 treated with endovascular therapy for atherosclerotic LEAD from July 1, 2005, to December 31, 2019. The main outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). Multivariate analysis was conducted using the Cox proportional hazard model to determine independent variables. We performed interaction analysis between corrected QT and other covariates and Kaplan-Meier analysis to compare the outcome of interest among the groups stratified by the tercile of QTc intervals. RESULTS A total of 504 patients [235 men (46.6%); mean age, 79.9 ± 6.2 years; mean QTc interval, 459 ± 33 msec] entered the final data analysis. We categorized the baseline patient characteristics according to terciles of QTc intervals. During the median follow-up time of 3.15 (interquartile ranges, 1.65-5.42) years, we noted 264 deaths and 145 MACEs. The 5-year rates of freedom from all-cause mortality (71% vs. 57% vs. 31%, P < 0.001) and MACEs (83% vs. 67% vs. 46%, P < 0.001) were significantly different among the tercile groups. Multivariate analysis showed that a 1-SD increase in the QTc interval increased the risk of all-cause mortality [hazard ratio (HR) 1.49, P < 0.001] and MACEs (HR 1.59, P < 0.001) after adjusting for other covariates. The interaction analysis showed that QTc interval and C-reactive protein levels were most strongly associated with death (HR = 4.88, 95% CI 3.09-7.73, interaction P < 0.001) and MACEs (HR = 7.83, 95% CI 4.14-14.79, interaction P < 0.001). CONCLUSIONS In elderly patients with symptomatic atherosclerotic LEAD, a prolonged QTc interval is associated with advanced limb ischemia, multiple medical comorbidities, increased risk of MACEs, and all-cause mortality.
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Affiliation(s)
- Yao-Ting Chang
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical, Foundation, New Taipei, Taiwan
| | - Shih-Jung Jang
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Kuan-Liang Liu
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Chien-An Hsieh
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Hsin-Hua Chou
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Kuan-Hung Yeh
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hsuan-Li Huang
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
| | - TRENDPAD Study Group
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
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18
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Cupelli M, Ginjupalli VKM, Chen L, Capecchi PL, Lazzerini PE, Boutjdir M, El-Sherif N. Contribution of cytokine-mediated prolongation of QTc interval to the multi-hit theory of Torsade de Pointes. Biochem Biophys Res Commun 2023; 655:82-89. [PMID: 36933311 DOI: 10.1016/j.bbrc.2023.02.060] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND Torsade de pointes is a potentially lethal polymorphic ventricular tachyarrhythmia that can occur in the setting of long QT syndrome (LQTS). LQTS is multi-hit in nature and multiple factors combine their effects leading to increased arrhythmic risk. While hypokalemia and multiple medications are accounted for in LQTS, the arrhythmogenic role of systemic inflammation is increasingly recognized but often overlooked. We tested the hypothesis that the inflammatory cytokine interleukin(IL)-6 will significantly increase the incidence of arrhythmia when combined with other pro-arrhythmic conditions (hypokalemia and the psychotropic medication, quetiapine). METHODS Guinea pigs were injected intraperitoneally with IL-6/soluble IL-6 receptor and QT changes were measured in vivo. Subsequently, hearts were cannulated via Langendorff perfusion for ex vivo optical mapping measurements of action potential duration (APD90) and arrhythmia inducibility. Computer simulations (MATLAB) were performed to investigate IKr inhibition at varying IL-6 and quetiapine concentrations. RESULTS IL-6 prolonged QTc in vivo guinea pigs from 306.74 ± 7.19 ms to 332.60 ± 8.75 ms (n = 8, p = .0021). Optical mapping on isolated hearts demonstrated APD prolongation in IL-6- vs saline groups (3Hz APD90:179.67 ± 2.47 ms vs 153.5 ± 7.86 ms, p = .0357). When hypokalemia was introduced, the APD90 increased to 195.8 ± 5.02 ms[IL-6] and 174.57 ± 10.7 ms[saline] (p = .2797), and when quetiapine was added to hypokalemia to 207.67 ± 3.03 ms[IL-6] and 191.37 ± 9.49 ms[saline] (p = .2449). After the addition of hypokalemia ± quetiapine, arrhythmia was induced in 75% of IL-6-treated hearts (n = 8), while in none of the control hearts (n = 6). Computer simulations demonstrated spontaneous depolarizations at ∼83% aggregate IKr inhibition. CONCLUSIONS Our experimental observations strongly suggest that controlling inflammation, specifically IL-6, could be a viable and important route for reducing QT prolongation and arrhythmia incidence in the clinical setting.
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Affiliation(s)
- Michael Cupelli
- Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, 11209, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Science University, New York, NY, 11203, USA
| | - Vamsi Krishna Murthy Ginjupalli
- Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, 11209, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Science University, New York, NY, 11203, USA
| | - Lu Chen
- Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, 11209, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Science University, New York, NY, 11203, USA
| | | | - Pietro Enea Lazzerini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy
| | - Mohamed Boutjdir
- Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, 11209, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Science University, New York, NY, 11203, USA; Department of Medicine, NYU School of Medicine, New York, NY, 10016, USA
| | - Nabil El-Sherif
- Cardiovascular Research Program, VA New York Harbor Healthcare System, New York, NY, 11209, USA; Department of Medicine, Cell Biology and Pharmacology, State University of New York Downstate Health Science University, New York, NY, 11203, USA.
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19
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Mojón-Álvarez D, Izquierdo A, Cubero-Gallego H, Calvo-Fernández A, Marrugat J, Pérez-Fernández S, Cabero P, Solà-Richarte C, Soler C, Farré N, Vaquerizo B. The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year. Front Cardiovasc Med 2023; 10:1140276. [PMID: 37089886 PMCID: PMC10117953 DOI: 10.3389/fcvm.2023.1140276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 03/21/2023] [Indexed: 04/08/2023] Open
Abstract
Background and objectiveProlonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up.MethodsWe conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed.ResultsThirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year.ConclusionsProlonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.
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Affiliation(s)
- Diana Mojón-Álvarez
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
| | - Andrea Izquierdo
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
| | - Héctor Cubero-Gallego
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- IMIM, Heart Disease Biomedical Research Group, Barcelona, Spain
| | - Alicia Calvo-Fernández
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
- Medicine Department, Pompeu Fabra University, Barcelona, Spain
| | - Jaume Marrugat
- CIBER Group in Epidemiology and Public Heath (CIBERCV), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- REGICOR (Registre Gironí del Cor) Study Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Silvia Pérez-Fernández
- Scientific Coordination Facility, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
| | - Paula Cabero
- Cardiology Department, Hospital del Mar, Barcelona, Spain
| | | | - Cristina Soler
- Cardiology Department, Hospital del Mar, Barcelona, Spain
| | - Núria Farré
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
- IMIM, Heart Disease Biomedical Research Group, Barcelona, Spain
- Medicine Department, Pompeu Fabra University, Barcelona, Spain
| | - Beatriz Vaquerizo
- Cardiology Department, Hospital del Mar, Barcelona, Spain
- Medicine Department, Autonomous University of Barcelona, Barcelona, Spain
- IMIM, Heart Disease Biomedical Research Group, Barcelona, Spain
- Medicine Department, Pompeu Fabra University, Barcelona, Spain
- CIBER Group in Epidemiology and Public Heath (CIBERCV), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- Correspondence: Beatriz Vaquerizo
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Left Ventricular Hypertrophy and Ventricular Tachyarrhythmia: The Role of Biomarkers. Int J Mol Sci 2023; 24:ijms24043881. [PMID: 36835293 PMCID: PMC9958550 DOI: 10.3390/ijms24043881] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/08/2023] [Accepted: 02/14/2023] [Indexed: 02/17/2023] Open
Abstract
Left ventricular hypertrophy (LVH) refers to a complex rebuilding of the left ventricle that can gradually lead to serious complications-heart failure and life-threatening ventricular arrhythmias. LVH is defined as an increase in the size of the left ventricle (i.e., anatomically), therefore the basic diagnosis detecting the increase in the LV size is the domain of imaging methods such as echocardiography and cardiac magnetic resonance. However, to evaluate the functional status indicating the gradual deterioration of the left ventricular myocardium, additional methods are available approaching the complex process of hypertrophic remodeling. The novel molecular and genetic biomarkers provide insights on the underlying processes, representing a potential basis for targeted therapy. This review summarizes the spectrum of the main biomarkers employed in the LVH valuation.
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21
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22
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Cardiac Involvement in Children Affected by COVID-19: Clinical Features and Diagnosis. Diagnostics (Basel) 2022; 13:diagnostics13010120. [PMID: 36611412 PMCID: PMC9818331 DOI: 10.3390/diagnostics13010120] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 12/24/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022] Open
Abstract
COVID-19 (Coronavirus disease 2019) in children is usually mild. However, multiple organ disorders associated with SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) have been detected with poor respiratory symptoms. Cardiac changes are noted in 17% to 75% of cases, which are associated with diagnostic difficulties in high-risk groups for the development of complications that are associated with myocardial damage by the SARS-CoV-2 virus. The objective of this review is to identify the most significant symptoms of cardiac involvement affected by COVID-19, which require in-depth examination. The authors analyzed publications from December 2019 to the October 2022, which were published in accessible local and international databases. According to the analysis data, the main sign of myocardial involvement was increasing as cardiomarkers in the patient's blood, in particular troponin I or troponin T. Many authors noted that the increased level of CRP (C-reactive protein) and NT-proBNP, which are accompanied by changes in the ECG (electrocardiogram) and EchoCG (echocardiography), as a rule, were nonspecific. However, the identified cardiac functional dysfunctions affected by SARS-CoV-2, required an cardiac MRI. The lack of timely diagnosis of myocardial involvements, especially in children at high risk for the development of complications associated with SARS-CoV-2 myocardial injury, can lead to death. The direct damage of the structural elements of myocardial blood vessels in patients with severe hypoxic changes resulted from respiratory failure caused by SARS-CoV-2 lung damage, with the development of severe acute diffuse alveolar damage and cell-mediated immune response and myocardial involvement affected by SARS-CoV-2 damage. In this article, the authors introduce a clinical case of a child who dead from inflammatory myocardities with COVID-19 in a background of congenital heart disease and T-cell immunodeficiency.
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23
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Sousa Oliveira CV, Moreno-Loaiza O, Figueiredo-Vanzan D, Peroba Ramos I, Mata-Santos H, Torres Bozza M, Neto Paiva C, Medei E. IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease. Front Immunol 2022; 13:1010257. [PMID: 36341442 PMCID: PMC9627615 DOI: 10.3389/fimmu.2022.1010257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 09/26/2022] [Indexed: 11/26/2022] Open
Abstract
Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1β mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1β remains elevated in Chagas disease patients, here we tested the role of IL-1β in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r−/−) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r−/− presented intervals like noninfected controls. Infected Il-1r−/− and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1–S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1β/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1β signaling, ruling out this mechanism is important to discourage further attempts of IL-1β blockade as a therapeutical measure.
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Affiliation(s)
- Camila Victória Sousa Oliveira
- Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Oscar Moreno-Loaiza
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | | | - Isalira Peroba Ramos
- National Center for Structural Biology and Bioimage (CENABIO), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Hilton Mata-Santos
- Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Marcelo Torres Bozza
- Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Claudia Neto Paiva
- Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- *Correspondence: Emiliano Medei, ; Claudia Neto Paiva,
| | - Emiliano Medei
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- National Center for Structural Biology and Bioimage (CENABIO), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- D’Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
- *Correspondence: Emiliano Medei, ; Claudia Neto Paiva,
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Zhan Y, Yue H, Liang W, Wu Z. Effects of COVID-19 on Arrhythmia. J Cardiovasc Dev Dis 2022; 9:jcdd9090292. [PMID: 36135437 PMCID: PMC9504579 DOI: 10.3390/jcdd9090292] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/19/2022] [Accepted: 09/01/2022] [Indexed: 01/08/2023] Open
Abstract
The World Health Organization announced that COVID-19, with SARS-CoV-2 as its pathogen, had become a pandemic on 11 March 2020. Today, the global epidemic situation is still serious. With the development of research, cardiovascular injury in patients with COVID-19, such as arrhythmia, myocardial injury, and heart failure, is the second major symptom in addition to respiratory symptoms, and cardiovascular injury is related to the prognosis and mortality of patients. The incidence of arrhythmia in COVID-19 patients ranges from 10% to 20%. The potential mechanisms include viral infection-induced angiotensin-converting enzyme 2 expression change, myocarditis, cytokine storm, cardiac injury, electrophysiological effects, hypoxemia, myocardial strain, electrolyte abnormalities, intravascular volume imbalance, drug toxicities and interactions, and stress response caused by virus infection. COVID-19 complicated with arrhythmia needs to be accounted for and integrated in management. This article reviews the incidence, potential mechanisms, and related management measures of arrhythmia in COVID-19 patients.
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Affiliation(s)
| | | | | | - Zhong Wu
- Correspondence: ; Tel.: +86-028-85422897
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25
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Isakadze N, Engels MC, Beer D, McClellan R, Yanek LR, Mondaloo B, Hays AG, Metkus TS, Calkins H, Barth AS. C-reactive Protein Elevation Is Associated With QTc Interval Prolongation in Patients Hospitalized With COVID-19. Front Cardiovasc Med 2022; 9:866146. [PMID: 35811700 PMCID: PMC9261932 DOI: 10.3389/fcvm.2022.866146] [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] [Received: 01/30/2022] [Accepted: 04/28/2022] [Indexed: 12/27/2022] Open
Abstract
Background The relationship between inflammation and corrected QT (QTc) interval prolongation is currently not well defined in patients with COVID-19. Objective This study aimed to assess the effect of marked interval changes in the inflammatory marker C-reactive protein (CRP) on QTc interval in patients hospitalized with COVID-19. Methods In this retrospective cohort study of hospitalized adult patients admitted with COVID-19 infection, we identified 85 patients who had markedly elevated CRP levels and serial measurements of an ECG and CRP during the same admission. We compared mean QTc interval duration, and other clinical and ECG characteristics between times when CRP values were high and low. We performed mixed-effects linear regression analysis to identify associations between CRP levels and QTc interval in univariable and adjusted models. Results Mean age was 58 ± 16 years, of which 39% were women, 41% were Black, and 25% were White. On average, the QTc interval calculated via the Bazett formula was 15 ms higher when the CRP values were “high” vs. “low” [447 ms (IQR 427–472 ms) and 432 ms (IQR 412–452 ms), respectively]. A 100 mg/L increase in CRP was associated with a 1.5 ms increase in QTc interval [β coefficient 0.15, 95% CI (0.06–0.24). In a fully adjusted model for sociodemographic, ECG, and clinical factors, the association remained significant (β coefficient 0.14, 95% CI 0.05–0.23). Conclusion An interval QTc interval prolongation is observed with a marked elevation in CRP levels in patients with COVID-19.
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Affiliation(s)
- Nino Isakadze
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Marc C. Engels
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Dominik Beer
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Rebecca McClellan
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Lisa R. Yanek
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Bahareh Mondaloo
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Allison G. Hays
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Thomas S. Metkus
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Hugh Calkins
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Andreas S. Barth
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- *Correspondence: Andreas S. Barth
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Banai A, Szekely Y, Lupu L, Borohovitz A, Levi E, Ghantous E, Taieb P, Hochstadt A, Banai S, Topilsky Y, Chorin E. QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection. Front Cardiovasc Med 2022; 9:869089. [PMID: 35757338 PMCID: PMC9223350 DOI: 10.3389/fcvm.2022.869089] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/11/2022] [Indexed: 01/08/2023] Open
Abstract
Background QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Materials and Methods A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3-3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06-2.68, p = 0.027). Conclusion Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.
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Affiliation(s)
- Ariel Banai
- Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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27
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De Gregori S, Falaschi F, Ballesio A, Fusco A, Cremonte E, Canta R, Sabatini U, Molinaro M, Soffiantini C, Nardone A, Vicentini A, De Silvestri A, Di Sabatino A. Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation. Drugs R D 2022; 22:155-163. [PMID: 35553396 PMCID: PMC9103606 DOI: 10.1007/s40268-022-00387-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ. METHODS We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with CHCQ. RESULTS Our data suggest that short-term hydroxychloroquine courses can generate significant CHCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with CHCQ. CONCLUSIONS The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation.
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Affiliation(s)
- Simona De Gregori
- Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Francesco Falaschi
- Internal Medicine 2, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
| | - Alessia Ballesio
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Alessandra Fusco
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Elisa Cremonte
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Roberta Canta
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Umberto Sabatini
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Mariadelfina Molinaro
- Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Carlo Soffiantini
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Alba Nardone
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Alessandro Vicentini
- Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Antonio Di Sabatino
- Internal Medicine 2, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
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Lazzerini PE, Accioli R, Acampa M, Zhang WH, Verrengia D, Cartocci A, Bacarelli MR, Xin X, Salvini V, Chen KS, Salvadori F, D’errico A, Bisogno S, Cevenini G, Marzotti T, Capecchi M, Laghi-Pasini F, Chen L, Capecchi PL, Boutjdir M. Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation. Front Cardiovasc Med 2022; 9:893681. [PMID: 35665254 PMCID: PMC9161021 DOI: 10.3389/fcvm.2022.893681] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/13/2022] [Indexed: 12/13/2022] Open
Abstract
Background Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms. Methods We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro. Results In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr). Conclusion For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.
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Affiliation(s)
- Pietro Enea Lazzerini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
- *Correspondence: Pietro Enea Lazzerini,
| | - Riccardo Accioli
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | | | - Wen-Hui Zhang
- National Standard Laboratory of Pharmacology for Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Pharmacy, Maanshan People’s Hospital, Maanshan, China
| | - Decoroso Verrengia
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | | | - Maria Romana Bacarelli
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Xiaofeng Xin
- Department of Respiration, Affiliated Jinling Hospital School of Medicine, Nanjing University, Nanjing, China
| | - Viola Salvini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Ke-Su Chen
- School of Medicine, Nanjing University, Nanjing, China
| | - Fabio Salvadori
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Antonio D’errico
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Stefania Bisogno
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Gabriele Cevenini
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Tommaso Marzotti
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Matteo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Franco Laghi-Pasini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Long Chen
- National Standard Laboratory of Pharmacology for Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Pier Leopoldo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Mohamed Boutjdir
- VA New York Harbor Healthcare System, New York, NY, United States
- SUNY Downstate Health Sciences University, New York, NY, United States
- NYU School of Medicine, New York, NY, United States
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Tarantino N, Della Rocca DG, Zou F, Lin A, Natale A, Di Biase L. Prevalence, Outcomes, and Management of Ventricular Arrhythmias in COVID-19 Patients. Card Electrophysiol Clin 2022; 14:11-20. [PMID: 35221078 PMCID: PMC8554003 DOI: 10.1016/j.ccep.2021.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
We review the current data on epidemiology, the clinical significance, the pathophysiologic mechanisms, and the treatment of VAs in the setting of COVID-19. VAs prevail in 0.15% to 8% of hospitalized patients, but only sustained and rapid tachyarrhythmias are purportedly associated with a significant increase in mortality. Multiple factors can elicit VAs, which are ultimately deemed to be a marker of severe systemic disease rather than a distinct cardiac condition. Even though the electrophysiologist plays a determinant role in the secondary prevention of VAs, a multidisciplinary approach is indispensable for primary prophylaxis and acute management.
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Affiliation(s)
- Nicola Tarantino
- Montefiore Medical Center, 111 E 210th street, Bronx, NY 10467, USA
| | - Domenico G Della Rocca
- Texas Cardiac Arrhythmia Institute at St. David's Medical Center, 3000 N I-35, Suite 720, Austin, TX 78705, USA
| | - Fengwei Zou
- Montefiore Medical Center, 111 E 210th street, Bronx, NY 10467, USA
| | - Aung Lin
- Montefiore Medical Center, 111 E 210th street, Bronx, NY 10467, USA
| | - Andrea Natale
- Texas Cardiac Arrhythmia Institute at St. David's Medical Center, 3000 N I-35, Suite 720, Austin, TX 78705, USA; Scripps Interventional Car, 9834 Genesee Ave, La Jolla, CA 92037, USA; Health Education Campus, 9501 Euclid Ave, Cleveland, OH 44106, USA
| | - Luigi Di Biase
- Montefiore Medical Center, 111 E 210th street, Bronx, NY 10467, USA; Texas Cardiac Arrhythmia Institute at St. David's Medical Center, 3000 N I-35, Suite 720, Austin, TX 78705, USA.
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30
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Sunkak S, Argun M, Celik B, Tasci O, Ozturk AB, Inan DB, Dogan M. Effects of azithromycin on ventricular repolarization in children with COVID-19. Rev Port Cardiol 2022; 41:551-556. [PMID: 35221464 PMCID: PMC8858685 DOI: 10.1016/j.repc.2021.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 04/18/2021] [Indexed: 11/29/2022] Open
Abstract
Introduction Azithromycin is used to treat pediatric COVID-19 patients. It can also prolong the QT interval in adults. This study assessed the effects of azithromycin on ventricular repolarization in children with COVID-19. Method The study prospectively enrolled children with COVID-19 who received azithromycin between July and August 2020. An electrocardiogram was performed before, one, three, and five days post-treatment. Using ImageJ®, the following parameters were measured: QT max, QT min, Tp-e max, and Tp-e min. The parameters QTc max, QTc min, Tp-ec max, Tp-ec min, QTcd, Tp-ecd, and the QTc/Tp-ec ratio were calculated using Bazett's formula. Results The study included 105 pediatric patients (mean age 9.8±5.3 years). The pretreatment heart rate was higher than after treatment (before 92 [79–108]/min vs. Day 1 82 [69–108)]/min vs. Day 3 80 [68–92.2]/min vs. Day 5 81 [70–92]/min; p=0.05). Conclusion Azithromycin does not affect the ventricular repolarization parameters on ECG in pediatric COVID-19 cases.
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31
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Zhu X, Wang Y, Xiao Y, Gao Q, Gao L, Zhang W, Xin X, Chen K, Srivastava U, Ginjupalli VKM, Cupelli M, Lazzerini PE, Capecchi PL, Chen L, Boutjdir M. Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases. Sci Rep 2022; 12:1075. [PMID: 35058480 PMCID: PMC8776801 DOI: 10.1038/s41598-022-04852-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 12/28/2021] [Indexed: 12/23/2022] Open
Abstract
Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood. The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ. IL-6, AZM and HCQ were concomitantly administered to guinea pigs in-vivo and in-vitro. Electrocardiograms, action potentials and ion-currents were analyzed. IL-6 alone or the combination AZM + HCQ induced mild to moderate reduction in heart rate, PR-interval and corrected QT (QTc) in-vivo and in-vitro. Notably, IL-6 alone was more potent than the combination of the two drugs in reducing heart rate, increasing PR-interval and QTc. In addition, the in-vivo or in-vitro combination of IL-6 + AZM + HCQ caused severe bradycardia, conduction abnormalities, QTc prolongation and asystole. These electrocardiographic abnormalities were attenuated in-vivo by tocilizumab (TCZ), a monoclonal antibody against IL-6 receptor, and are due in part to the prolongation of action potential duration and selective inhibition of Na+, Ca2+ and K+ currents. Inflammation confers greater risk for arrhythmia than the drug combination therapy. As such, in the setting of elevated IL-6 during inflammation caution must be taken when co-administering drugs known to predispose to fatal arrhythmias and TCZ could be an important player as a novel anti-arrhythmic agent. Thus, identifying inflammation as a critical culprit is essential for proper management.
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Ashraf H, Ghafouri P, Kazemian S, Soleimani A, Sadat Naseri A, Karbalai S, Kazemi Saeid A. Hydroxychloroquine alone or in combination with azithromycin and corrected QT prolongation in COVID-19 patients: A systematic review. World J Meta-Anal 2021; 9:557-567. [DOI: 10.13105/wjma.v9.i6.557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/01/2021] [Accepted: 11/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019 (COVID-19), these drugs are still the only options available. Moreover, the safety of these drugs is yet to be confirmed. A serious concern is the occurrence of various cardiac arrhythmias, particularly QT prolongation.
AIM To summarize the incidence and estimate the risk of QT interval prolongation in patients scheduling for conventional treatment (hydroxychloroquine alone or in combination with azithromycin) for COVID-19.
METHODS We comprehensively searched Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials databases until October 31, 2020 for all eligible studies under the considered keywords COVID-19, arrhythmia, QT interval, therapy, azithromycin, and hydroxychloroquine until. The study protocols were established in compliance with PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-Analysis – Protocols), and a nine-star Newcastle-Ottawa Scale scoring system was used to assess the methodological quality of all eligible studies. Outcome measures were corrected QT (QTc) prolongation, cardiac arrhythmias, or sudden cardiac death.
RESULTS Fifteen studies enrolling 8298 patients with targeted COVID-19 therapeutic regimes were included. The eligible studies found a significant increase in the mean QTc interval following treatment with the described medications compared to baseline QTc with weighted standard differences in means of 0.766. The pooled prevalence rate of QTc prolongation was estimated to be 9.2% (95% confidence interval: 4.5% to 18.1%).
CONCLUSION Hydroxychloroquine ± azithromycin regimen can significantly increase the risk of developing QTc prolongation.
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Affiliation(s)
- Haleh Ashraf
- Research Development Center, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
- Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
| | - Parham Ghafouri
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran 11367-46911, Iran
- School of medicine, Tehran University of Medical Science, Tehran 11367-46911, Iran
| | - Sina Kazemian
- Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran 11367-46911, Iran
| | - Abbas Soleimani
- Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
| | - Azadeh Sadat Naseri
- Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
| | - Shahrokh Karbalai
- Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
| | - Ali Kazemi Saeid
- Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
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Lazzerini PE, Cantara S, Bertolozzi I, Accioli R, Salvini V, Cartocci A, D'Errico A, Sestini F, Bisogno S, Cevenini G, Capecchi M, Laghi-Pasini F, Castagna MG, Acampa M, Boutjdir M, Capecchi PL. Transient Hypogonadism Is Associated With Heart Rate-Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men. J Am Heart Assoc 2021; 11:e023371. [PMID: 34935398 PMCID: PMC9075210 DOI: 10.1161/jaha.121.023371] [Citation(s) in RCA: 6] [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] [Indexed: 01/08/2023]
Abstract
Background Systemic inflammation and male hypogonadism are 2 increasingly recognized “nonconventional” risk factors for long‐QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate–corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. Methods and Results We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C‐reactive protein and interleukin‐6 levels. Reduction of testosterone levels, which also inversely correlated with 17‐β estradiol over time, significantly contributed to inflammation‐induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C‐reactive protein, testosterone, and 17‐β estradiol levels; in these patients, increased C‐reactive protein and reduced testosterone were associated with a worse short‐term outcome of the arrhythmia. Conclusions During systemic inflammatory activation, interleukin‐6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen‐to‐estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long‐QT syndrome/TdP risk in men.
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Affiliation(s)
| | - Silvia Cantara
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | - Iacopo Bertolozzi
- Cardiology Intensive Therapy Unit Department of Internal Medicine Nuovo Ospedale San Giovanni di Dio Florence Italy
| | - Riccardo Accioli
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | - Viola Salvini
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | | | - Antonio D'Errico
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | - Fausta Sestini
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | - Stefania Bisogno
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | | | - Matteo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | - Franco Laghi-Pasini
- Department of Medical Sciences, Surgery and Neurosciences University of Siena Italy
| | | | | | - Mohamed Boutjdir
- VA New York Harbor Healthcare SystemSUNY Downstate Health Sciences University New York NY.,NYU School of Medicine New York NY
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Anand P, Mayfield JJ, He B, Khaira KB. Unusual T-wave Changes and Extreme QTc Prolongation in a 71-year-old man with Asymptomatic COVID Infection. HeartRhythm Case Rep 2021; 8:99-101. [PMID: 34804796 PMCID: PMC8596657 DOI: 10.1016/j.hrcr.2021.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Affiliation(s)
- Priyanka Anand
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington
| | - Jacob J. Mayfield
- Division of Cardiology, University of Washington School of Medicine, Seattle, Washington
| | - Beixin He
- Division of Cardiology, University of Washington School of Medicine, Seattle, Washington
- Division of Cardiology, VA Puget Sound Health Care System, Seattle, Washington
| | - Kavita B. Khaira
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington
- Division of Cardiology, University of Washington School of Medicine, Seattle, Washington
- Division of Cardiology, VA Puget Sound Health Care System, Seattle, Washington
- Address reprint requests and correspondence: Dr Kavita B. Khaira, VA Puget Sound Healthcare System, University of Washington, 1660 S Columbia Way, Seattle, WA 98108.
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Kusmiati T, Mertaniasih NM, Eko Putranto JN, Suprapti B, Soedarsono, Luthfah N, Koesoemoprodjo W, Sari AP. The role of C-Reactive protein as an inflammatory marker to predict prolonged QTc interval in rifampicin-resistant tuberculosis patients: A case-control study. Ann Med Surg (Lond) 2021; 70:102899. [PMID: 34691435 PMCID: PMC8519798 DOI: 10.1016/j.amsu.2021.102899] [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: 08/13/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 01/08/2023] Open
Abstract
Background long-term use of anti-tuberculosis drugs (ATD) increases the risk of QTc prolongation, while C-reactive protein (CRP) can be used as an inflammatory marker of Mycobacterium tuberculosis infection. Objective: correlation of CRP on the QTc interval in Rifampicin-resistant tuberculosis (RR-TB) patients with the short regimen. Methods An observational study was conducted in Rifampicin-resistant tuberculosis (RR-TB) patients from 2 groups, patients on intensive phase and patients on continuation phase. CRP levels were measured from blood samples and measured automatically using the immunoturbidimetric assay. QTc interval was calculated using electrocardiography. Levels of CRP levels and QTc interval between the 2 groups were analyzed. The statistical analysis used includes the independent t-test, Mann Whitney test, and Rank Spearman test with p = 0.05. Results Forty-five eligible RR-TB patients were included in this study. CRP levels and QTc intervals between 2 groups (intensive and continuation phase) showed significant difference with p < 0.001 but found no significant correlation of CRP levels and QTc interval in both intensive and continuation phase with p = 0.226 and 0.805, respectively. A higher level of CRP strongly indicated the inflammation caused by RR-TB infection at the early phase of the disease, but not correlated with QTc interval in RR-TB patients. Conclusion Levels of CRP and QTc interval do not correlate in RR-TB patients and can not be used to be the marker of QTc prolongation in RR-TB Patients.
CRP levels are markers used for diagnosis and monitoring in RR-TB patients. Decrease CRP levels in RR-TB patients are don't a marker of QTc prolongation. The significant between intensive and continuation phase of CRP and QTc interval in RR-TB patients.
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Affiliation(s)
- Tutik Kusmiati
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Ni Made Mertaniasih
- Department of Clinical Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Johanes Nugroho Eko Putranto
- Department of Vascular and Cardiology Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Budi Suprapti
- Faculty of Pharmacy, Universitas Airlangga - Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
| | - Soedarsono
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Nadya Luthfah
- Department of Vascular and Cardiology Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Winariani Koesoemoprodjo
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Aryani Prawita Sari
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
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Kusmiati T, Mertaniasih NM, Eko Putranto JN, Suprapti B, Soedarsono, Luthfah N, Koesoemoprodjo W, Sari AP. Correlation of inflammatory cytokines on corrected QT interval in rifampicin-resistant tuberculosis patients. Ann Med Surg (Lond) 2021; 70:102862. [PMID: 34584687 PMCID: PMC8452756 DOI: 10.1016/j.amsu.2021.102862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/12/2021] [Accepted: 09/13/2021] [Indexed: 01/08/2023] Open
Abstract
Background The cases of Rifampicin-Resistant Tuberculosis (RR-TB) in our country have increased every year and RR-TB deaths are thought to be caused by prolongation of the QTc interval due to side effects of anti-tuberculosis drugs. Thus, cytokines are needed to be used as early markers of prolongation of the QTc interval in RR-TB patients. Objective This study aims to analyze the correlation of inflammatory cytokines on QTc interval in RR-TB patients who received shorter regimens. Methods This study uses a case-control study with a time series conducted in the period September 2019 to February 2020 in one of the referral hospitals for Tuberculosis in Indonesia. Cytokines levels from blood samples were measured using the ELISA method, while QTc intervals were automatically recorded using an electrocardiography machine. The statistical analysis used was the Chi-square test, Man Whitney test, Independence t-test, and Spearman-rank test with p < 0.05. Results There was no significant correlation between inflammatory cytokines and QTc prolongation in intensive phase which TNF-α value (6.8 pg/ml; r = 0.207; p = 0.281), IL-1β (20.13 pg/ml; r = 0.128; p = 0.509), and IL-6 (43.17 pg/ml; r = -0.028; p = 0.886). Meanwhile, in the continuation phase, the values for TNF-α (4.79 pg/ml; r = 0.046; p = 0.865), IL-1β (7.42 pg/ml; r = -0.223; p = 0.406), and IL- 6 (40.61 pg/ml; r = -0.147; p = 0.586). Conclusion inflammatory cytokines (TNF-α, IL-1β, and IL-6) cannot be used to identify QTc interval prolongation in RR-TB patients who received shorter regimens.
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Key Words
- BMI, Body mass index
- Ca, Calcium
- IL-1β
- IL-1β, interleukin-1β
- IL-6
- IL-6, interleukin 6
- K, Potassium
- MDR, multidrug resistance
- QTc prolongation
- RR-TB
- RR-TB, Rifampicin-Resistant Tuberculosis
- TB, tuberculosis
- TNF-α
- TNF-α, Tumor necrosis factor alpha
- WHO, World Health Organization
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Affiliation(s)
- Tutik Kusmiati
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Ni Made Mertaniasih
- Department of Clinical Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Johanes Nugroho Eko Putranto
- Department of Vascular and Cardiology Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Budi Suprapti
- Faculty of Pharmacy, Universitas Airlangga - Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
| | - Soedarsono
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Nadya Luthfah
- Department of Vascular and Cardiology Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Winariani Koesoemoprodjo
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Aryani Prawita Sari
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
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Lazzerini PE, Laghi-Pasini F, Boutjdir M, Capecchi PL. Anti-Ro/SSA Antibodies and the Autoimmune Long-QT Syndrome. Front Med (Lausanne) 2021; 8:730161. [PMID: 34552948 PMCID: PMC8450397 DOI: 10.3389/fmed.2021.730161] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 08/11/2021] [Indexed: 01/08/2023] Open
Abstract
Autoimmunity is increasingly recognized as a novel pathogenic mechanism for cardiac arrhythmias. Several arrhythmogenic autoantibodies have been identified, cross-reacting with different types of surface proteins critically involved in the cardiomyocyte electrophysiology, primarily ion channels (autoimmune cardiac channelopathies). Specifically, some of these autoantibodies can prolong the action potential duration leading to acquired long-QT syndrome (LQTS), a condition known to increase the risk of life-threatening ventricular arrhythmias, particularly Torsades de Pointes (TdP). The most investigated form of autoimmune LQTS is associated with the presence of circulating anti-Ro/SSA-antibodies, frequently found in patients with autoimmune diseases (AD), but also in a significant proportion of apparently healthy subjects of the general population. Accumulating evidence indicates that anti-Ro/SSA-antibodies can markedly delay the ventricular repolarization via a direct inhibitory cross-reaction with the extracellular pore region of the human-ether-a-go-go-related (hERG) potassium channel, resulting in a higher propensity for anti-Ro/SSA-positive subjects to develop LQTS and ventricular arrhythmias/TdP. Recent population data demonstrate that the risk of LQTS in subjects with circulating anti-Ro/SSA antibodies is significantly increased independent of a history of overt AD, intriguingly suggesting that these autoantibodies may silently contribute to a number of cases of ventricular arrhythmias and cardiac arrest in the general population. In this review, we highlight the current knowledge in this topic providing complementary basic, clinical and population health perspectives.
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Affiliation(s)
- Pietro Enea Lazzerini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Franco Laghi-Pasini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Mohamed Boutjdir
- Veterans Affairs New York Harbor Healthcare System, State University of New York Downstate Medical Center, New York, NY, United States.,New York University School of Medicine, New York, NY, United States
| | - Pier Leopoldo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
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Bisceglia I, Gabrielli D, Canale ML, Gallucci G, Parrini I, Turazza FM, Russo G, Maurea N, Quagliariello V, Lestuzzi C, Oliva S, Di Fusco SA, Lucà F, Tarantini L, Trambaiolo P, Gulizia MM, Colivicchi F. ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO). Eur Heart J Suppl 2021; 23:C128-C153. [PMID: 34456641 PMCID: PMC8388610 DOI: 10.1093/eurheartj/suab067] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.
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Affiliation(s)
- Irma Bisceglia
- Integrated Cardiology Services, Cardio-Thoracic-Vascular Department, Azienda Ospedaliera San Camillo Forlanini, Roma, Italy
| | - Domenico Gabrielli
- Cardiology Unit, Cardio-Thoracic-Vascular Department, Azienda Ospedaliera San Camillo Forlanini, Roma, Italy
| | - Maria Laura Canale
- Cardiology Department, Nuovo Ospedale Versilia Lido Di Camaiore, LU, Italy
| | | | - Iris Parrini
- Cardiology Department, Ospedale Mauriziano Umberto I, Torino, Italy
| | | | - Giulia Russo
- Cardiovascular and Sports Medicine Department, ASUGI Trieste, Trieste, Italy
| | - Nicola Maurea
- Cardiology Department, Fondazione Pascale, Napoli, Italy
| | | | - Chiara Lestuzzi
- Cardiology Department, Centro di Riferimento Oncologico (CRO), Aviano, PN, Italy
| | - Stefano Oliva
- Cardio-Oncology Department, Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Stefania Angela Di Fusco
- Clinical and Rehabilitation Cardiology Department, Presidio Ospedaliero San Filippo Neri, ASL Roma 1, Roma, Italy
| | - Fabiana Lucà
- Cardiology Department, Grande Osp. Metropol-Bianchi Melacrino-Morelli, Reggio Calabria, Italy
| | - Luigi Tarantini
- Cardiology Department, Presidio Ospedaliero. Santa Maria Nuova—AUSL RE IRCCS, Reggio Emilia, Italy
| | | | - Michele Massimo Gulizia
- Cardiology Department, Azienda di Rilievo Nazionale e Alta Specializzazione “Garibaldi”, Catania, Italy
- Fondazione per il Tuo cuore—Heart Care Foundation, Firenze, Italy
| | - Furio Colivicchi
- Clinical and Rehabilitation Cardiology Department, Presidio Ospedaliero San Filippo Neri, ASL Roma 1, Roma, Italy
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Baracaldo-Santamaría D, Llinás-Caballero K, Corso-Ramirez JM, Restrepo CM, Dominguez-Dominguez CA, Fonseca-Mendoza DJ, Calderon-Ospina CA. Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation. Int J Mol Sci 2021; 22:8090. [PMID: 34360853 PMCID: PMC8347245 DOI: 10.3390/ijms22158090] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/04/2021] [Accepted: 07/06/2021] [Indexed: 12/22/2022] Open
Abstract
Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.
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Affiliation(s)
- Daniela Baracaldo-Santamaría
- School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (D.B.-S.); (J.M.C.-R.); (C.A.D.-D.)
| | - Kevin Llinás-Caballero
- GENIUROS Research Group, Center for Research in Genetics and Genomics (CIGGUR), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (K.L.-C.); (C.M.R.); (D.J.F.-M.)
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia
| | - Julián Miguel Corso-Ramirez
- School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (D.B.-S.); (J.M.C.-R.); (C.A.D.-D.)
| | - Carlos Martín Restrepo
- GENIUROS Research Group, Center for Research in Genetics and Genomics (CIGGUR), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (K.L.-C.); (C.M.R.); (D.J.F.-M.)
| | | | - Dora Janeth Fonseca-Mendoza
- GENIUROS Research Group, Center for Research in Genetics and Genomics (CIGGUR), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (K.L.-C.); (C.M.R.); (D.J.F.-M.)
| | - Carlos Alberto Calderon-Ospina
- GENIUROS Research Group, Center for Research in Genetics and Genomics (CIGGUR), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia; (K.L.-C.); (C.M.R.); (D.J.F.-M.)
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Otherwise Unexplained Transient QTc Prolongation in a Patient Admitted with COVID Disease. Case Rep Cardiol 2021; 2021:9931405. [PMID: 34158979 PMCID: PMC8168475 DOI: 10.1155/2021/9931405] [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: 03/17/2021] [Revised: 04/25/2021] [Accepted: 05/20/2021] [Indexed: 11/18/2022] Open
Abstract
Background. Several cardiovascular manifestations of coronavirus disease 2019 (COVID-19) have been previously described. QT prolongation has been reported in COVID-19 infection in association with medications such as azithromycin, hydroxychloroquine, and chloroquine but has not previously been reported as a direct result of COVID-19 infection. Case summary. We report the case of a 65-year-old female who developed a prolonged corrected QT interval (QTc) during a hospital admission with COVID-19. This patient was not on any QT prolonging treatment, serum electrolytes were normal, and there was no identifiable reversible cause for the QTc lengthening. Daily serial ECGs during admission showed resolution of the ventricular repolarization abnormality in synchronization with resolution of her COVID-19 viral illness. Discussions. Although there have been reports of QTc prolongation in COVID-19 patients, previous reports of this are for patients receiving medication that causes QT prolongation. This case uniquely demonstrates the development and resolution of this temporary ventricular repolarization abnormality in a patient with a structurally normal heart with no evidence of myocardial fibrosis or edema on cardiac MRI, that is unexplained by other confounding factors, such as medication. This suggests there may be a direct association between COVID-19 and temporary QTc prolongation.
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Qiu H, Li HW, Zhang SH, Zhou XG, Li WP. Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report. World J Clin Cases 2021; 9:2899-2907. [PMID: 33969075 PMCID: PMC8058677 DOI: 10.12998/wjcc.v9.i12.2899] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 02/07/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND QT interval prolongation can induce torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Recently, an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset. Moreover, recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome (LQTS) and TdP development.
CASE SUMMARY A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks. The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein. Once after a high fever, the patient suddenly lost consciousness, and electrocardiogram (ECG) showed transient TdP onset after frequent premature ventricular contraction. The patient recovered sinus rhythm and consciousness spontaneously, and post-TdP ECG revealed a prolonged QTc interval of 560 ms. The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease (AOSD). There was no evidence of cardiac involvement. After the AOSD diagnosis, discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval. The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2 (c.1370C>T) and AKAP9 (c.7725A>C). During the 2-year follow-up period, the patient had no recurrence of any arrhythmia and maintained normal QTc interval.
CONCLUSION This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset. Genetic analysis should be considered to identify individuals at high risk of developing TdP.
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Affiliation(s)
- Hui Qiu
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Hong-Wei Li
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Shu-Hong Zhang
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xiao-Ge Zhou
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Wei-Ping Li
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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Lee TL, Hsuan CF, Wu CC, Hung WC, Tsai IT, Wei CT, Yu TH, Lu IC, Chung FM, Lee YJ, Lu YC. Association between Triglyceride Glucose Index and Corrected QT Prolongation in Chinese Male Steelworkers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:4020. [PMID: 33921213 PMCID: PMC8069503 DOI: 10.3390/ijerph18084020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 01/08/2023]
Abstract
Objectives: Increased triglyceride glucose (TyG) index appears to be linked to carotid and coronary atherosclerosis and calcifications and possesses an elevated future risk of developing cardiovascular disease. Corrected QT (QTc) interval prolongation is associated with ventricular arrhythmias and sudden cardiac death, and a high prevalence of prolonged QTc interval was previously reported in blue-collar workers. The purpose of this study was to find the possible causal inter-relationship between TyG index and QTc interval in a large population of Chinese male steelworkers. Methods: A total of 3189 male workers from two steel plants were enrolled. They responded to a cross-sectional questionnaire on basic attributes and lifestyle, including sleep patterns. All workers in the two plants underwent periodic health checkups, including twelve-lead electrocardiography. Structural equation modeling (SEM) was used to assess the direct and indirect effects of TyG index on QTc interval. Results: With increasing TyG index tertile, the male steelworkers had an increased QTc interval. Applying multivariate analysis, TyG index was associated independently with the odds of QTc prolongation (adjusted odds ratio = 2.73, 95% confidence interval = 1.39-5.24, p = 0.004). SEM revealed that TyG index, hypertension, obesity, lifestyle, white blood cell (WBC) count, and liver function had statistically significant direct effects on QTc interval. Furthermore, TyG index also had an indirect effect on QTc interval through hypertension, obesity, WBC count, and liver function. Moreover, lifestyle had an indirect effect on QTc interval through TyG index. The final model explained 14% of the variability in QTc interval. Conclusions: An increased TyG index was associated with QTc interval prolongation in this study, and SEM delineated possible causal pathways and inter-relationships of the risk factors contributing to the occurrence of QTc prolongation among Chinese male steelworkers.
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Affiliation(s)
- Thung-Lip Lee
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - Chin-Feng Hsuan
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - I-Ting Tsai
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Department of Emergency, E-Da Hospital, Kaohsiung 82445, Taiwan
| | - Ching-Ting Wei
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung 82445, Taiwan
- Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan
- Department of Electrical Engineering, I-Shou University, Kaohsiung 82445, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
| | - I-Cheng Lu
- Department of Occupational Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan;
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan; (T.-L.L.); (C.-F.H.); (C.-C.W.); (W.-C.H.); (T.-H.Y.); (F.-M.C.)
| | - Yau-Jiunn Lee
- Lee’s Endocrinologic Clinic, Pingtung 90000, Taiwan;
| | - Yung-Chuan Lu
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
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Chen PH, Tsai SY, Pan CH, Chang HM, Chen YL, Su SS, Chen CC, Kuo CJ. Age Effect on Incidence, Physical, and Psychiatric Comorbidity for Sudden Cardiac Death in Schizophrenia: Effet de l'âge sur l'incidence, la comorbidité physique et psychiatrique de la mort cardiaque subite dans la schizophrénie. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2021; 66:367-375. [PMID: 32799653 PMCID: PMC8172351 DOI: 10.1177/0706743720948429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The pathogenesis of sudden cardiac death may differ between younger and older adults in schizophrenia, but evidence remains scant. This study investigated the age effect on the incidence and risk of the physical and psychiatric comorbidity for sudden cardiac death. METHODS Using 2000 to 2016 data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, we identified a national cohort of 170,322 patients with schizophrenia, 1,836 of whom had a sudden cardiac death. Standardized mortality ratios (SMRs) were estimated. Hazard ratios and population attributable fractions of distinctive comorbidities for sudden cardiac death were assessed. RESULTS The SMRs of sudden cardiac death were all >1.00 across each age group for both sexes, with the highest SMR in male patients aged <35 years (30.88, 95% CI: 26.18-36.18). The fractions of sudden cardiac death attributable to hypertension and congestive heart failure noticeably increased with age. By contrast, the fraction attributable to drug-induced mental disorder decreased with age. Additionally, chronic hepatic disease and sleep disorder increased the risk of sudden cardiac death in patients aged <35 years. Dementia and organic mental disorder elevated the risk in patients aged between 35-54 years. Ischemic heart disease raised the risk in patients aged ≥55 years. CONCLUSIONS The risk is increased across the lifespan in schizophrenia, particularly for younger male patients. Furthermore, physical and psychiatric comorbidities have age-dependent risks. The findings suggest that prevention strategies targeted toward sudden cardiac death in patients with schizophrenia must consider the age effect.
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Affiliation(s)
- Pao-Huan Chen
- Department of Psychiatry, 63474Taipei Medical University Hospital, Taipei.,Psychiatric Research Center, 63474Taipei Medical University Hospital, Taipei.,Department of Psychiatry, School of Medicine, College of Medicine, 63474Taipei Medical University, Taipei
| | - Shang-Ying Tsai
- Department of Psychiatry, 63474Taipei Medical University Hospital, Taipei.,Psychiatric Research Center, 63474Taipei Medical University Hospital, Taipei.,Department of Psychiatry, School of Medicine, College of Medicine, 63474Taipei Medical University, Taipei
| | - Chun-Hung Pan
- Taipei City Psychiatric Center, 433112Taipei City Hospital, Taipei.,Department of Psychology, National Chengchi University, Taipei
| | - Hu-Ming Chang
- Taipei City Psychiatric Center, 433112Taipei City Hospital, Taipei
| | - Yi-Lung Chen
- Taipei City Psychiatric Center, 433112Taipei City Hospital, Taipei
| | - Sheng-Siang Su
- Taipei City Psychiatric Center, 433112Taipei City Hospital, Taipei
| | - Chiao-Chicy Chen
- Department of Psychiatry, School of Medicine, College of Medicine, 63474Taipei Medical University, Taipei.,Department of Psychiatry, 36897Mackay Memorial Hospital, Taipei.,Department of Psychiatry, Mackay Medical College, Taipei
| | - Chian-Jue Kuo
- Psychiatric Research Center, 63474Taipei Medical University Hospital, Taipei.,Department of Psychiatry, School of Medicine, College of Medicine, 63474Taipei Medical University, Taipei.,Taipei City Psychiatric Center, 433112Taipei City Hospital, Taipei
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Morales X, Garnica D, Isaza D, Isaza N, Durán-Torres F. Syncope due to non-sustained episodes of Torsade de Pointes associated to androgen-deprivation therapy use: a case presentation. BMC Cardiovasc Disord 2021; 21:136. [PMID: 33711933 PMCID: PMC7953541 DOI: 10.1186/s12872-021-01945-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/04/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Abiraterone is a medication frequently used for metastatic castrate-resistant prostate cancer. We report a case of non-sustained episodes of TdP associated with severe hypokalemia due to androgen-deprivation therapy. Few case presentations describe this association; the novelty lies in the potentially lethal cardiovascular events among cancer patients receiving hormonal therapy. CASE PRESENTATION A 70-year-old male presented with recurrent syncope without prodrome. ECG revealed frequent ventricular ectopy, non-sustained episodes of TdP, and severe hypomagnesemia and hypokalemia. During potassium and magnesium infusion for repletion, the patient underwent temporary transvenous atrial pacing. As part of the work-up, coronary angiography revealed a mild coronary artery disease, and transthoracic echocardiogram showed a moderately depressed ejection fraction. After electrolyte disturbances were corrected, the QT interval normalized, and transvenous pacing was no longer necessary. Abiraterone was discontinued during the admission, and the patient returned to baseline. CONCLUSIONS Cancer treatment is complex and requires a multidisciplinary approach. We presented a case of non-sustained TdP associated with androgen-deprivation therapy in an elderly patient with mild coronary artery disease and moderately reduced ejection fraction. Close follow-up and increased awareness are required in patients with hormonal treatment, especially in the setting of other cardiovascular risk factors.
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Affiliation(s)
- Ximena Morales
- School of Medicine and Health Sciences, Internal Medicine Program, Fundación Cardioinfantil, Universidad del Rosario, Carrera 24 #63C-69, Bogotá, Colombia.
| | - Diego Garnica
- Fundación Cardioinfantil, Universidad del Bosque, Bogotá, Colombia
| | - Daniel Isaza
- Division of Cardiology, Fundación Cardioinfantil, Bogotá, Colombia
| | - Nicolas Isaza
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Felipe Durán-Torres
- School of Medicine and Health Sciences, Public Health Research Group, Universidad del Rosario, Bogotá, Colombia
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45
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Richez C, Flipo RM, Berenbaum F, Cantagrel A, Claudepierre P, Debiais F, Dieudé P, Goupille P, Roux C, Schaeverbeke T, Wendling D, Pham T, Thomas T. Prise en charge des patients atteints de maladies rhumatismales pendant la pandémie de COVID-19 : la Société française de rhumatologie répond aux questions fréquentes posées jusqu’en mai 2020. REVUE DU RHUMATISME 2021; 88:93-100. [PMID: 33488063 PMCID: PMC7813495 DOI: 10.1016/j.rhum.2021.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 05/19/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Christophe Richez
- FHU ACRONIM, CHU de Bordeaux, place Amélie-Raba-Léon, 33076 Bordeaux, France
| | - René-Marc Flipo
- Service de rhumatologie, centre hospitalier régional universitaire de Lille, hôpital Roger-Salengro, rue du Professeur Émile-Laine, 59037 Lille cedex, France
| | - Francis Berenbaum
- Service de rhumatologie, CHU de Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 755571 Paris cedex 12, France
| | - Alain Cantagrel
- Service de rhumatologie, CHU de Toulouse, Hôpital Purpan, place du Docteur Baylac, TSA 40031, 31059 Toulouse cedex 9, France
| | - Pascal Claudepierre
- Service de rhumatologie, CHU de Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France
| | - Françoise Debiais
- Service de rhumatologie, CHU, 2, rue de la Milétrie, BP 577, 86021 Poitiers cedex, France
| | - Philippe Dieudé
- Service de rhumatologie, groupe hospitalier universitaire Bichat-Claude Bernard, 46, rue Henri-Huchard, 75018 Paris, France
| | - Philippe Goupille
- Service de rhumatologie, centre hospitalier régional universitaire de Tours, hôpital Trousseau, 37044 Tours cedex 9, France
| | - Christian Roux
- Service de rhumatologie, CHU de Cochin, 27, rue du Faubourg Saint-Jacques, 75679 Paris cedex 14, France
| | | | - Daniel Wendling
- Service de rhumatologie, CHU de Jean-Minjoz, 1, boulevard Fleming, 25030 Besançon cedex, France
| | - Thao Pham
- Service de rhumatologie, CHU de Sainte-Marguerite, 270, boulevard de Sainte-Marguerite, 13274 Marseille cedex 9, France
| | - Thierry Thomas
- Department of Rheumatology, CHU de Saint-Étienne, Hôpital Nord, Saint-Étienne, France
- Inserm U1059, université de Lyon, université Jean-Monnet, Saint-Étienne, France
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46
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Lyon AR, Citro R, Schneider B, Morel O, Ghadri JR, Templin C, Omerovic E. Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:902-921. [PMID: 33602474 DOI: 10.1016/j.jacc.2020.10.060] [Citation(s) in RCA: 181] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 10/13/2020] [Accepted: 10/19/2020] [Indexed: 01/09/2023]
Abstract
Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.
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Affiliation(s)
- Alexander R Lyon
- Department of Cardiology, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom.
| | - Rodolfo Citro
- Cardio-Thoracic and Vascular Department, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy
| | | | - Olivier Morel
- Department of Cardiology, University of Strasbourg, UMR INSERM 1260 Regenerative Nanomedicine, Strasbourg, France
| | - Jelena R Ghadri
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Christian Templin
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Elmir Omerovic
- Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. https://twitter.com/ElmirOmerovic2
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Wu W, Lu C, Liang Y, Zhang H, Deng C, Wang Q, Xu Q, Tan B, Zhou C, Song J. Electrocardiographic effect of artemisinin-piperaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine treatment in falciparum malaria patients. Rev Soc Bras Med Trop 2021; 54:e05362020. [PMID: 33605379 PMCID: PMC7891559 DOI: 10.1590/0037-8682-0536-2020] [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] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 12/15/2020] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.
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Affiliation(s)
- Wanting Wu
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Chenguang Lu
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Yuan Liang
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
| | - Hongying Zhang
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Changsheng Deng
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Qi Wang
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Qin Xu
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
| | - Bo Tan
- Guangzhou University of Chinese Medicine, Institute of Tropical Medicine, Guangzhou, Guangdong, People’s Republic of China
| | - Chongjun Zhou
- Guangzhou University of Chinese Medicine, Institute of Tropical Medicine, Guangzhou, Guangdong, People’s Republic of China
| | - Jianping Song
- Guangzhou University of Chinese Medicine, Artemisinin Research Center, Guangzhou, Guangdong, People’s Republic of China
- Guangzhou University of Chinese Medicine, Sci-tech Industrial Park, Guanzhou, Guangdong, People’s Republic of China
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48
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The relationship between corrected QT interval and neutrophil to lymphocyte ratio in patients with acute coronary syndrome. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.867770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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49
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Shah RR. Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing. J Clin Pharm Ther 2021; 46:17-27. [PMID: 32981089 PMCID: PMC7537228 DOI: 10.1111/jcpt.13267] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 08/18/2020] [Indexed: 02/07/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Non-clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ-associated reduction in viral load from small studies in COVID-19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed. METHODS Published studies and rapidly emerging data were reviewed to gather evidence on safety and efficacy of CQ and HCQ in patients with COVID-19 infection or as prophylaxis. The focus is on clinically relevant efficacy endpoints and their adverse effects on QT interval. RESULTS AND DISCUSSION At the doses used, the two agents, given alone or with azithromycin (AZM), are not effective in COVID-19 infection. The choice of (typically subtherapeutic) dosing regimens, influenced partly by "QT-phobia," varied widely and seems anecdotal without any pharmacologically reliable supporting clinical evidence. A substantial proportion of patients receiving CQ/HCQ/AZM regimen developed QTc interval prolongation, many with absolute QTc interval exceeding the potential proarrhythmic threshold, but very few developed proarrhythmia. WHAT IS NEW AND CONCLUSION The strategy to repurpose CQ/HCQ to combat COVID-19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT-related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID-19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally.
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50
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Capecchi PL, Lazzerini PE, Volterrani L, Mazzei MA, Rossetti B, Zanelli G, Bennett D, Bargagli E, Franchi F, Cameli M, Valente S, Cantarini L, Frediani B. Antirheumatic agents in covid-19: is IL-6 the right target? Ann Rheum Dis 2021; 80:e2. [PMID: 32299796 DOI: 10.1136/annrheumdis-2020-217523] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 01/08/2023]
Affiliation(s)
- Pier Leopoldo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences, Section of Internal Medicine, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Pietro Enea Lazzerini
- Department of Medical Sciences, Surgery and Neurosciences, Section of Internal Medicine, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Luca Volterrani
- Department of Medical Sciences, Surgery and Neurosciences, Section of Radiology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Maria Antonietta Mazzei
- Department of Medical Sciences, Surgery and Neurosciences, Section of Radiology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Barbara Rossetti
- Section of Infectious Diseases, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Giacomo Zanelli
- Department of Medical Biotechnologies, Section of Infectious Diseases, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - David Bennett
- Section of Pneumology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Elena Bargagli
- Department of Medical Sciences, Surgery and Neurosciences, Section of Pneumology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Federico Franchi
- Department of Medical Sciences, Surgery and Neurosciences, Section of Intensive Care, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Matteo Cameli
- Department of Medical Biotechnologies, Section of Cardiology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Serafina Valente
- Section of Cardiology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Luca Cantarini
- Department of Medical Sciences, Surgery and Neurosciences, Section of Rheumatology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
| | - Bruno Frediani
- Department of Medical Sciences, Surgery and Neurosciences, Section of Rheumatology, COVID-19 Unit, Siena University Hospital, Siena, Toscana, Italy
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