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Sartorio A, Burrei G, Cristin L, Zoncapè M, Carlin M, Tadiello E, Minuz P, Dalbeni A, Romano S. QTc Prolongation to Predict Mortality in Patients Admitted with COVID-19 Infection: An Observational Study. Curr Vasc Pharmacol 2024; 22:106-121. [PMID: 38073101 DOI: 10.2174/0115701611250248231114114557] [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: 02/21/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 06/14/2024]
Abstract
BACKGROUND Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), characterized by pulmonary infection ranging from asymptomatic forms to respiratory insufficiency and death. Evidence of cardiac involvement in COVID-19 is increasing, and systemic inflammation or direct heart damage by SARS-CoV-2 can prolong the corrected QT interval (QTc). METHODS In this observational study, a total of 333 consecutive patients admitted to the Covid Center of Verona University Hospital from November 2020 to April 2021 were included. Patients with bundle branch block, pacemaker-controlled heart rhythm and heart rate >120 beats/min were excluded. A complete electrocardiogram (ECG) was performed at admission, and QTc values of ≥440 ms for males and ≥460 ms for females were considered prolonged. RESULTS Overall, 153 patients had prolonged QTc (45.5%). In multivariate logistic regression analysis, male sex (odds ratio (OR)=6.612, p=0.046), troponin (OR=1.04, p=0.015) and lymphocyte count (OR=3.047, p=0.019) were independently associated with QTc prolongation. Multivariate logistic regression showed that QTc was independently associated with mortality (OR=4.598, p=0.036). Age, sex, the ratio between the partial pressure of oxygen (PaO2) and the fraction of inspired oxygen (FiO2) (P/F), and fibrosis-4 index for liver fibrosis (FIB-4) were also independently associated with mortality. CONCLUSION QTc interval prolongation appears to be a frequent finding in patients with COVID-19. Moreover, prolonged QTc may be predictive of more severe forms of COVID-19 and worse outcome.
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Affiliation(s)
- Andrea Sartorio
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Giulia Burrei
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Luca Cristin
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Mirko Zoncapè
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Michele Carlin
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Enrico Tadiello
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Pietro Minuz
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Andrea Dalbeni
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
| | - Simone Romano
- Division of Internal Medicine C, Department of Medicine, University of Verona, Italy
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The Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, Arbelo E, Barbato E, Bartorelli AL, Baumbach A, Behr ER, Berti S, Bueno H, Capodanno D, Cappato R, Chieffo A, Collet JP, Cuisset T, de Simone G, Delgado V, Dendale P, Dudek D, Edvardsen T, Elvan A, González-Juanatey JR, Gori M, Grobbee D, Guzik TJ, Halvorsen S, Haude M, Heidbuchel H, Hindricks G, Ibanez B, Karam N, Katus H, Klok FA, Konstantinides SV, Landmesser U, Leclercq C, Leonardi S, Lettino M, Marenzi G, Mauri J, Metra M, Morici N, Mueller C, Petronio AS, Polovina MM, Potpara T, Praz F, Prendergast B, Prescott E, Price S, Pruszczyk P, Rodríguez-Leor O, Roffi M, Romaguera R, Rosenkranz S, Sarkozy A, Scherrenberg M, Seferovic P, Senni M, Spera FR, Stefanini G, Thiele H, Tomasoni D, Torracca L, Touyz RM, Wilde AA, Williams B. ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2-care pathways, treatment, and follow-up. Cardiovasc Res 2022; 118:1618-1666. [PMID: 34864876 PMCID: PMC8690236 DOI: 10.1093/cvr/cvab343] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
AIMS Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. METHODS AND RESULTS A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. CONCLUSION This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
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Safety of Short-Term Treatments with Oral Chloroquine and Hydroxychloroquine in Patients with and without COVID-19: A Systematic Review. Pharmaceuticals (Basel) 2022; 15:ph15050634. [PMID: 35631460 PMCID: PMC9144263 DOI: 10.3390/ph15050634] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/27/2022] [Accepted: 05/13/2022] [Indexed: 01/09/2023] Open
Abstract
Chloroquine (CQ) and hydroxychloroquine (HCQ) have recently become the focus of global attention as possible treatments for Coronavirus Disease 2019 (COVID-19). The current systematic review aims to assess their safety in short treatments (≤14 days), whether used alone or in combination with other drugs. Following the PRISMA and SWiM recommendations, a search was conducted using four health databases for all relevant English-, Chinese-, and Spanish-language studies from inception through 30 July 2021. Patients treated for any condition and with any comparator were included. The outcomes of interest were early drug adverse effects and their frequency. A total of 254 articles met the inclusion criteria, including case and case-control reports as well as cross-sectional, cohort, and randomised studies. The results were summarised either qualitatively in table or narrative form or, when possible (99 studies), quantitatively in terms of adverse event frequencies. Quality evaluation was conducted using the CARE, STROBE, and JADAD tools. This systematic review showed that safety depended on drug indication. In COVID-19 patients, cardiac adverse effects, such as corrected QT interval prolongation, were relatively frequent (0–27.3% and up to 33% if combined with azithromycin), though the risk of torsade de pointes was low. Compared to non-COVID-19 patients, COVID-19 patients experienced a higher frequency of cardiac adverse effects regardless of the regimen used. Dermatological adverse effects affected 0–10% of patients with autoimmune diseases and COVID-19. A broad spectrum of neuropsychiatric adverse effects affected patients treated with CQ for malaria with variable frequencies and some cases were reported in COVID-19 patients. Gastrointestinal adverse effects occurred regardless of drug indication affecting 0–50% of patients. In conclusion, CQ and HCQ are two safe drugs widely used in the treatment of malaria and autoimmune diseases. However, recent findings on their cardiac and neuropsychiatric adverse effects should be considered if these drugs were to be proposed as antivirals again.
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Kiriacos CJ, Khedr MR, Tadros M, Youness RA. Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha. Front Oncol 2022; 12:837408. [PMID: 35664773 PMCID: PMC9157490 DOI: 10.3389/fonc.2022.837408] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/21/2022] [Indexed: 12/12/2022] Open
Abstract
Background Being "positive" has been one of the most frustrating words anyone could hear since the end of 2019. This word had been overused globally due to the high infectious nature of SARS-CoV-2. All citizens are at risk of being infected with SARS-CoV-2, but a red warning sign has been directed towards cancer and immune-compromised patients in particular. These groups of patients are not only more prone to catch the virus but also more predisposed to its deadly consequences, something that urged the research community to seek other effective and safe solutions that could be used as a protective measurement for cancer and autoimmune patients during the pandemic. Aim The authors aimed to turn the spotlight on specific herbal remedies that showed potential anticancer activity, immuno-modulatory roles, and promising anti-SARS-CoV-2 actions. Methodology To attain the purpose of the review, the research was conducted at the States National Library of Medicine (PubMed). To search databases, the descriptors used were as follows: "COVID-19"/"SARS-CoV-2", "Herbal Drugs", "Autoimmune diseases", "Rheumatoid Arthritis", "Asthma", "Multiple Sclerosis", "Systemic Lupus Erythematosus" "Nutraceuticals", "Matcha", "EGCG", "Quercetin", "Cancer", and key molecular pathways. Results This manuscript reviewed most of the herbal drugs that showed a triple action concerning anticancer, immunomodulation, and anti-SARS-CoV-2 activities. Special attention was directed towards "matcha" as a novel potential protective and therapeutic agent for cancer and immunocompromised patients during the SARS-CoV-2 pandemic. Conclusion This review sheds light on the pivotal role of "matcha" as a tri-acting herbal tea having a potent antitumorigenic effect, immunomodulatory role, and proven anti-SARS-CoV-2 activity, thus providing a powerful shield for high-risk patients such as cancer and autoimmune patients during the pandemic.
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Affiliation(s)
- Caroline Joseph Kiriacos
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Monika Rafik Khedr
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Miray Tadros
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Rana A. Youness
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
- Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, Egypt
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Fallani E, Cevenini F, Lazzerini PE, Verdini A, Saponara S. Off-Label Use of Hydroxychloroquine in COVID-19: Analysis of Reports of Suspected Adverse Reactions From the Italian National Network of Pharmacovigilance. J Clin Pharmacol 2022; 62:646-655. [PMID: 34802170 PMCID: PMC9011412 DOI: 10.1002/jcph.2006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/16/2021] [Indexed: 11/10/2022]
Abstract
This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of COVID-19, occurring in Italy in the period March to May 2020. The analysis of the combination therapy with azithromycin or/and lopinavir/ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analyzed for their incidence, seriousness, outcome, coadministered drugs, and Medical Dictionary for Regulatory Activities classification. A total of 306 reports were gathered for the quarter of 2020: 54% nonserious and 46% serious, and half of the latter required either the hospitalization or its prolongation. However, most of them were either completely recovered (26%) or in the process of recovery (45%), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53% nonserious and 47% serious, but no deaths had been reported. Diarrhea, prolonged QT interval, and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADRs, QT prolongation, and diarrhea significantly increased with hydroxychloroquine dosage. Coadministration of lopinavir/ritonavir and hydroxychloroquine showed a positive correlation with diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination therapy with azithromycin was another independent predictor of a serious ADR. Off-label use of hydroxychloroquine for COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the infection.
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Affiliation(s)
- Elettra Fallani
- Dipartimento di Scienze della VitaUniversità di SienaSienaItaly
| | - Fabio Cevenini
- Dipartimento di Economia e ManagementUniversità di TrentoTrentoItaly
| | | | | | - Simona Saponara
- Dipartimento di Scienze della VitaUniversità di SienaSienaItaly
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The Task Force for the management of COVID-19 of the European Society of Cardiology, Baigent C, Windecker S, Andreini D, Arbelo E, Barbato E, Bartorelli AL, Baumbach A, Behr ER, Berti S, Bueno H, Capodanno D, Cappato R, Chieffo A, Collet JP, Cuisset T, de Simone G, Delgado V, Dendale P, Dudek D, Edvardsen T, Elvan A, González-Juanatey JR, Gori M, Grobbee D, Guzik TJ, Halvorsen S, Haude M, Heidbuchel H, Hindricks G, Ibanez B, Karam N, Katus H, Klok FA, Konstantinides SV, Landmesser U, Leclercq C, Leonardi S, Lettino M, Marenzi G, Mauri J, Metra M, Morici N, Mueller C, Petronio AS, Polovina MM, Potpara T, Praz F, Prendergast B, Prescott E, Price S, Pruszczyk P, Rodríguez-Leor O, Roffi M, Romaguera R, Rosenkranz S, Sarkozy A, Scherrenberg M, Seferovic P, Senni M, Spera FR, Stefanini G, Thiele H, Tomasoni D, Torracca L, Touyz RM, Wilde AA, Williams B. ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2-care pathways, treatment, and follow-up. Eur Heart J 2022; 43:1059-1103. [PMID: 34791154 PMCID: PMC8690006 DOI: 10.1093/eurheartj/ehab697] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/08/2021] [Accepted: 09/13/2021] [Indexed: 02/07/2023] Open
Abstract
AIMS Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. METHODS AND RESULTS A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. CONCLUSION This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.
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El Kadri M, Al Falasi O, Ahmed R, Al Awadhi A, Altaha Z, Hillis A, Panikkaveetil B, Abdalla S, Ansel Benette H, Almubarak A, Saifuddin M, Alattar Y, Oulhaj A, AlKaabi S. Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study. BMJ Open 2022; 12:e051579. [PMID: 35140148 PMCID: PMC8829836 DOI: 10.1136/bmjopen-2021-051579] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE To evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths. DESIGN A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas. SETTING A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates. PARTICIPANTS 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020. INTERVENTIONS Treatment with hydroxychloroquine alone or in combination with azithromycin for at least 24 hours and with a baseline ECG and at least one ECG after 24 hours of therapy. MAIN OUTCOME MEASURES Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment. RESULTS The baseline QTc(Bazett) was 427.6±25.4 ms and the maximum QTc(Bazett) during treatment was 439.2±30.4 ms (p<0.001). Severe QTc prolongation (QTc ≥500 ms) was observed in 1.7%-3.3% of patients (Fridericia and Bazett, respectively). There were no cases of polymorphic ventricular arrhythmia or hydroxychloroquine-related arrhythmic death. QTc prolongation was more pronounced in combination therapy compared with hydroxychloroquine alone (22.2 ms vs 11.0 ms, p<0.001) and in patients with higher COVID-19 clinical severity (asymptomatic: 428.4±25.4 ms, severe COVID-19 infection: 452.7±35.7 ms, p<0.001). The overall in-hospital mortality was 3.97% and deceased patients had longer on-therapy QTc(Bazett) than survivors (459.8±21.4 ms vs 438.4±29.9 ms, p<0.001). CONCLUSIONS The incidence of severe QTc prolongation with hydroxychloroquine was low and not associated with ventricular arrhythmia. The safety concerns surrounding the use of hydroxychloroquine may have been overestimated; however, caution should be exercised when using hydroxychloroquine in patients with risk factors for QT prolongation.
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Affiliation(s)
- Moutaz El Kadri
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
- College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE
| | - Omar Al Falasi
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Rizwan Ahmed
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
- College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE
| | - Ahlam Al Awadhi
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Zainab Altaha
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Amany Hillis
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Basheer Panikkaveetil
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Sara Abdalla
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Honey Ansel Benette
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Adhba Almubarak
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | | | - Yousef Alattar
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Abderrahim Oulhaj
- College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Salem AlKaabi
- Cardiology Department, Sheikh Khalifa Medical City, Abu Dhabi, UAE
- Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
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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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Desmarais J, Rosenbaum JT, Costenbader KH, Ginzler EM, Fett N, Goodman S, O'Dell J, Pineau CA, Schmajuk G, Werth VP, Link MS, Kovacs R. American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity. Arthritis Rheumatol 2021; 73:2151-2160. [PMID: 34697918 DOI: 10.1002/art.41934] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022]
Abstract
Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.
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Affiliation(s)
| | - James T Rosenbaum
- Oregon Health & Science University and Legacy Devers Eye Institute, Portland, Oregon
| | | | - Ellen M Ginzler
- State University of New York Downstate Health Sciences University, Brooklyn
| | - Nicole Fett
- Oregon Health & Science University, Portland
| | - Susan Goodman
- Hospital for Special Surgery, Weill Cornell Medicine, New York, New York
| | - James O'Dell
- University of Nebraska Medical Center and Omaha VA Hospital, Omaha, Nebraska
| | | | - Gabriela Schmajuk
- University of California San Francisco, San Francisco VA Medical Center, and Philip R. Lee Institute for Health Policy, San Francisco, California
| | - Victoria P Werth
- University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, Pennsylvania
| | - Mark S Link
- University of Texas Southwestern Medical Center, Dallas
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Mangona E, Sandonato E, Brothers TN, Pawasauskas J. Drug-Induced QTc Prolongation: What We Know and Where We Are Going. Curr Drug Saf 2021; 17:100-113. [PMID: 34551700 DOI: 10.2174/1574886316666210922153059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 06/17/2021] [Accepted: 08/29/2021] [Indexed: 11/22/2022]
Abstract
Drug-induced QTc prolongation is a concerning electrocardiogram (ECG) abnormality. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. The Arizona Center for Education and Research on Therapeutics (AzCERT) has classified QTc prolonging therapeutic classes such as antiarrhythmics, antipsychotics, anti-infectives, and others. AzCERT criteria categorizes medications into three risk categories: "known," "possible," and "conditional risk" of QTc prolongation and Torsades de Pointes. The list of QTc prolonging medications continues to expand as new drug classes are approved and studied. Risk factors for QTc prolongation can be delineated into modifiable or non-modifiable. A validated risk scoring tool may be utilized to predict the likelihood of prolongation in patients receiving AzCERT classified medication. The resultant risk score may be applied to a clinical decision support system which offers mitigation strategies. Mitigation strategies including discontinuation of possible offending agents with selection of an alternative agent, assessment of potential drug interactions or dose adjustments through pharmacokinetic and pharmacodynamic monitoring, and initiation of both ECG and electrolyte monitoring are essential to prevent a drug-induced arrhythmia. The challenges presented by the COVID-19 pandemic have led to the development of innovative continuous monitoring technology, increasing protection for both patients and healthcare workers. Early intervention strategies may reduce adverse events and improve clinical outcomes in patients identified to be at risk of QTc prolongation.
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Affiliation(s)
- Erinn Mangona
- Department of Pharmacy Practice, University of Rhode Island, Kingston. United States
| | - Elisa Sandonato
- Department of Pharmacy Practice, University of Rhode Island, Kingston. United States
| | - Todd N Brothers
- Department of Pharmacy Practice, University of Rhode Island, Kingston. United States
| | - Jayne Pawasauskas
- Department of Pharmacy Practice, University of Rhode Island, Kingston. United States
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Haghjoo M, Golipra R, Kheirkhah J, Golabchi A, Shahabi J, Oni‐Heris S, Sami R, Tajmirriahi M, Saravi M, Khatami M, Varnasseri M, Kiarsi M, Hejazi SF, Yousefzadeh Rahaghi M, Taherkhani M, Ashraf H, Keshmiri MS, Akbarzadeh MA, Bozorgi A, Mottaghizadeh F, Hedayat B, Heidarali M, Hajhossein Talasaz A. Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: Results of a multicenter national survey. Int J Clin Pract 2021; 75:e14182. [PMID: 33759318 PMCID: PMC8250253 DOI: 10.1111/ijcp.14182] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), and these arrhythmic side effects have not been adequately addressed in COVID-19 patients treated with these repurposed medications. METHODS This is the prospective study of 2403 patients hospitalised at 13 hospitals within the COVID-19 epicentres of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation, and secondary outcomes were incidences of TdP and death. RESULTS Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc ≥ 500 ms and ∆QTc ≥ 60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or beta-blocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP was predicted by treatment with lopinavir-ritonavir, simultaneous amiodarone or furosemide administration and hypokalaemia during treatment. CONCLUSION This cohort showed significant QTc prolongation with all COVID-19 medications studied, however, life-threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir-ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.
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Affiliation(s)
- Majid Haghjoo
- Cardiac Electrophysiology Research CenterRajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
| | - Reza Golipra
- Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
| | - Jalal Kheirkhah
- Department of CardiologySchool of MedicineHeshmat HospitalGuilan University of Medical SciencesRashtIran
| | - Allahyar Golabchi
- Shahid Beheshti HospitalKashan University of Medical SciencesKashanIran
| | - Javad Shahabi
- Heart Failure Research CenterCardiovascular Research InstituteIsfahan University of Medical SciencesIsfahanIran
| | - Saeed Oni‐Heris
- Shahid Beheshti HospitalKashan University of Medical SciencesKashanIran
| | - Ramin Sami
- Department of Internal MedicineSchool of MedicineIsfahan University of Medical SciencesIsfahanIran
| | - Marzieh Tajmirriahi
- Hypertension Research CenterIsfahan Cardiovascular Research InstituteIsfahan University of Medical ScienceIsfahanIran
| | - Mehrdad Saravi
- Clinical Research Development UnitSchool of MedicineBabol University of Medical ScienceBabolIran
| | - Mozhdeh Khatami
- Imam Sajad HospitalIran University of Medical SciencesShahryarIran
| | - Mehran Varnasseri
- Infectious and Tropical Diseases Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran
| | - Mohammadreza Kiarsi
- Atherosclerosis Research CenterAhvaz University of Medical SciencesAhvazIran
| | | | | | - Maryam Taherkhani
- Loghman Hakim HospitalShahid Beheshti University of Medical SciencesTehranIran
| | - Haleh Ashraf
- Research Development CenterSina HospitalTehran University of Medical SciencesTehranIran
| | - Mohammad Sadegh Keshmiri
- Lung Transplantation Research CenterNational Research Institute of Tuberculosis and Lung DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | | | - Ali Bozorgi
- Tehran Heart CenterTehran University of Medical SciencesTehranIran
| | - Fateme Mottaghizadeh
- Cardiovascular Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Behnam Hedayat
- Tehran Heart CenterTehran University of Medical SciencesTehranIran
| | - Mona Heidarali
- Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
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12
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Torsade de pointes associated with chloroquine, hydroxychloroquine, and azithromycin: a retrospective analysis of individual case safety reports from VigiBase. Eur J Clin Pharmacol 2021; 77:1513-1521. [PMID: 33938974 PMCID: PMC8089128 DOI: 10.1007/s00228-021-03133-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 04/03/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches. METHODS The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated. RESULTS One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34). CONCLUSIONS The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.
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Multiple drugs. REACTIONS WEEKLY 2021. [PMCID: PMC7791948 DOI: 10.1007/s40278-021-89079-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Redefining the Prognostic Value of High-Sensitivity Troponin in COVID-19 Patients: The Importance of Concomitant Coronary Artery Disease. J Clin Med 2020; 9:jcm9103263. [PMID: 33053826 PMCID: PMC7601151 DOI: 10.3390/jcm9103263] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/05/2020] [Accepted: 10/09/2020] [Indexed: 12/18/2022] Open
Abstract
Background: Although studies assessing cardiovascular comorbidities and myocardial injury in Coronavirus disease 2019 (COVID-19) patients have been published, no reports focused on clinical outcomes of myocardial injury in patients with and without chronic coronary syndromes (CCS) are currently available. Methods: In this study, consecutive COVID-19 patients admitted to four different institutions were screened for enrolment. Patients were divided into two groups (CCS vs. no-CCS). Association with in-hospital mortality and related predictors represented the main study outcome; myocardial injury and its predictors were deemed secondary outcomes. Results: A total of 674 COVID-19 patients were enrolled, 112 (16.6%) with an established history of CCS. Myocardial injury occurred in 43.8% patients with CCS vs. 14.4% patients without CCS, as confirmed by high-sensitivity cardiac troponin (hs-cTn) elevation on admission or during hospitalization. The mortality rate in the CCS cohort was nearly three-fold higher. After adjusting for disease severity, myocardial injury resulted significantly associated with in-hospital mortality in the no-CCS group but not in CCS patients. Conclusions: Patients with CCS and COVID-19 showed high mortality rate. Myocardial injury may be a bystander in CCS patients and COVID-19, while in patients without known history of CCS, myocardial injury has a significant role in predicting poor outcomes.
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