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1
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Yao Z, Liang M, Zhu S. Infectious factors in myocarditis: a comprehensive review of common and rare pathogens. Egypt Heart J 2024; 76:64. [PMID: 38789885 PMCID: PMC11126555 DOI: 10.1186/s43044-024-00493-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Myocarditis is a significant health threat today, with infectious agents being the most common cause. Accurate diagnosis of the etiology of infectious myocarditis is crucial for effective treatment. MAIN BODY Infectious myocarditis can be caused by viruses, prokaryotes, parasites, and fungi. Viral infections are typically the primary cause. However, some rare opportunistic pathogens can also damage heart muscle cells in patients with immunodeficiencies, neoplasms and those who have undergone heart surgery. CONCLUSIONS This article reviews research on common and rare pathogens of infectious myocarditis, emphasizing the complexity of its etiology, with the aim of helping clinicians make an accurate diagnosis of infectious myocarditis.
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Affiliation(s)
- Zongjie Yao
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qindao, China.
| | - Mingjun Liang
- Department of Intensive Care Medicine, Shanghai Six People's Hospital Affilicated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Simin Zhu
- Wuhan Third Hospital-Tongren Hospital of Wuhan University, Wuhan, China
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2
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Panagiotides NG, Poledniczek M, Andreas M, Hülsmann M, Kocher AA, Kopp CW, Piechota-Polanczyk A, Weidenhammer A, Pavo N, Wadowski PP. Myocardial Oedema as a Consequence of Viral Infection and Persistence-A Narrative Review with Focus on COVID-19 and Post COVID Sequelae. Viruses 2024; 16:121. [PMID: 38257821 PMCID: PMC10818479 DOI: 10.3390/v16010121] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/02/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.
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Affiliation(s)
- Noel G. Panagiotides
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Michael Poledniczek
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
| | - Martin Andreas
- Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria; (M.A.); (A.A.K.)
| | - Martin Hülsmann
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Alfred A. Kocher
- Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria; (M.A.); (A.A.K.)
| | - Christoph W. Kopp
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
| | | | - Annika Weidenhammer
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Noemi Pavo
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Patricia P. Wadowski
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
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Baumeier C, Harms D, Aleshcheva G, Gross U, Escher F, Schultheiss HP. Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches. J Clin Med 2023; 12:5050. [PMID: 37568452 PMCID: PMC10419903 DOI: 10.3390/jcm12155050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches.
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Affiliation(s)
- Christian Baumeier
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (D.H.); (G.A.); (U.G.); (H.-P.S.)
| | - Dominik Harms
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (D.H.); (G.A.); (U.G.); (H.-P.S.)
- Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany
| | - Ganna Aleshcheva
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (D.H.); (G.A.); (U.G.); (H.-P.S.)
| | - Ulrich Gross
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (D.H.); (G.A.); (U.G.); (H.-P.S.)
| | - Felicitas Escher
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Virchow Klinikum, 13353 Berlin, Germany;
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany
| | - Heinz-Peter Schultheiss
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (D.H.); (G.A.); (U.G.); (H.-P.S.)
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4
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Matsumori A. Novel Biomarkers of Inflammation for the Management of Diabetes: Immunoglobulin-Free Light Chains. Biomedicines 2022; 10:biomedicines10030666. [PMID: 35327468 PMCID: PMC8945380 DOI: 10.3390/biomedicines10030666] [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: 02/21/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an essential role in the activation and development of B cells, and the activation of NF-κB is critical in the inflammation and development of diabetes mellitus. Recently, immunoglobulin-free light chain (FLC) λ was found to be increased in the sera of patients with diabetes mellitus, and the FLC λ and κ/λ ratios are more specific and sensitive markers for the diagnosis of diabetes relative to glycated hemoglobin A1c. Thus, FLCs may be promising biomarkers of inflammation that could relate to the activation of NF-κB. We suggest that NF-κB could be a target for an anti-inflammatory strategy in preventing and treating diabetes when FLCs are modified. FLCs could be a surrogate endpoint in the management of diabetes. In this review, the role of inflammation in the pathogenesis of diabetes, as well as the novel inflammatory biomarkers of FLCs for the management of diabetes, are discussed.
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Affiliation(s)
- Akira Matsumori
- Clinical Research Center, Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan
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5
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Schultheiss HP, Baumeier C, Pietsch H, Bock CT, Poller W, Escher F. Cardiovascular consequences of viral infections: from COVID to other viral diseases. Cardiovasc Res 2021; 117:2610-2623. [PMID: 34609508 PMCID: PMC8500164 DOI: 10.1093/cvr/cvab315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 09/28/2021] [Indexed: 12/15/2022] Open
Abstract
Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.
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Affiliation(s)
| | - Christian Baumeier
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, Berlin, Germany
| | - Heiko Pietsch
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, Berlin, Germany
- Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 13353, Germany
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - C -Thomas Bock
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin 13353 Germany
- Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
| | - Wolfgang Poller
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
- Department of Cardiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin12203, Germany
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 13353, Germany
| | - Felicitas Escher
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, Berlin, Germany
- Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 13353, Germany
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
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Schultheiss HP, Baumeier C, Aleshcheva G, Bock CT, Escher F. Viral Myocarditis-From Pathophysiology to Treatment. J Clin Med 2021; 10:5240. [PMID: 34830522 PMCID: PMC8623269 DOI: 10.3390/jcm10225240] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/06/2021] [Accepted: 11/08/2021] [Indexed: 12/17/2022] Open
Abstract
The diagnosis of acute and chronic myocarditis remains a challenge for clinicians. Characterization of this disease has been hampered by its diverse etiologies and heterogeneous clinical presentations. Most cases of myocarditis are caused by infectious agents. Despite successful research in the last few years, the pathophysiology of viral myocarditis and its sequelae leading to severe heart failure with a poor prognosis is not fully understood and represents a significant public health issue globally. Most likely, at a certain point, besides viral persistence, several etiological types merge into a common pathogenic autoimmune process leading to chronic inflammation and tissue remodeling, ultimately resulting in the clinical phenotype of dilated cardiomyopathy. Understanding the underlying molecular mechanisms is necessary to assess the prognosis of patients and is fundamental to appropriate specific and personalized therapeutic strategies. To reach this clinical prerequisite, there is the need for advanced diagnostic tools, including an endomyocardial biopsy and guidelines to optimize the management of this disease. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has currently led to the worst pandemic in a century and has awakened a special sensitivity throughout the world to viral infections. This work aims to summarize the pathophysiology of viral myocarditis, advanced diagnostic methods and the current state of treatment options.
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Affiliation(s)
- Heinz-Peter Schultheiss
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (C.B.); (G.A.); (F.E.)
| | - Christian Baumeier
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (C.B.); (G.A.); (F.E.)
| | - Ganna Aleshcheva
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (C.B.); (G.A.); (F.E.)
| | - C.-Thomas Bock
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany;
- Institute of Tropical Medicine, University of Tuebingen, 72074 Tuebingen, Germany
| | - Felicitas Escher
- Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany; (C.B.); (G.A.); (F.E.)
- Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, 13353 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
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7
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Haykal M, Matsumori A, Saleh A, Fayez M, Negm H, Shalaby M, Bassuony S. Diagnosis and treatment of HCV heart diseases. Expert Rev Cardiovasc Ther 2021; 19:493-499. [PMID: 33861939 DOI: 10.1080/14779072.2021.1917383] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important cause of a variety of otherwise unexplained heart diseases and myocardial injury. A high prevalence of HCV infection has been noted in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy and myocarditis. Various arrhythmias, conduction disturbances and QT prolongation were also associated with HCV infection. A possible role of HCV infection in the pathogenesis of diabetes and atherosclerosis, and the role of immunogenetics of HCV cardiomyopathies is discussed. Recent studies suggest that mononuclear cells may be the major target of HCV, and clinical applications to test this new hypothesis are discussed. AREAS COVERED In this review, we will evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders. EXPERT OPINION HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.
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Affiliation(s)
- Mohammad Haykal
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Akira Matsumori
- Clinical Research Center, Kyoto Medical Center, Kyoto, Japan
| | - Ahmed Saleh
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Moatez Fayez
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Hany Negm
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Mohammad Shalaby
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Samar Bassuony
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
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8
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Pennisi G, Spatola F, DI Marco L, DI Martino V, DI Marco V. Impact of Direct-Acting Antivirals (daas) on cardiovascular diseases in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:254-263. [PMID: 33971709 DOI: 10.23736/s2724-5985.21.02875-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In the last years the hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. This review aims to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.
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Affiliation(s)
- Grazia Pennisi
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy -
| | - Federica Spatola
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Lorenza DI Marco
- Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia, Modena, Italy
| | - Vincenzo DI Martino
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Vito DI Marco
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
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Arya S, Kumar P, Tiwari B, Belwal S, Saxena S, Abbas H. What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review. Indian J Crit Care Med 2020; 24:1251-1255. [PMID: 33446981 PMCID: PMC7775933 DOI: 10.5005/jp-journals-10071-23695] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Objectives Impairment of cardiac function and arrhythmias often coexist in patients with liver diseases. Many studies have proved this coexistence and put forward various theories toward its pathophysiology. This narrative review tries to find the answers with supporting evidence on five main questions: Materials and methods Clinical evidence was obtained by using search engines, namely, Cochrane Library, PubMed, and Google Scholar. Studies published in journals in the English language, between January 1969 and December 2019, which mentioned the relationship between cardiac arrhythmia and liver disease, were included. We used the keywords: jaundice, bilirubin, arrhythmia, ECG, QTc interval, QT dispersion, liver, and cirrhosis. Relevant animal or human studies answering the five main questions were extracted and reviewed. Conclusion The evidence included in our review sheds light on the fact that approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy (CC) and there has been an association between liver abnormalities and cardiac pathology. The present review also supports that there exists a strong association between high levels of serum bilirubin levels and cardiac arrhythmias, QTc value can be relied upon as a risk factor for predicting imminent arrhythmias, and that it is associated with mortality. Its basic pathophysiology can be explained by the potential action of bile acids in prolonging the QT interval. It also causes cardiac hypertrophy and apoptosis of cardiomyocytes leading to cardiac dysfunction. How to cite this article Arya S, Kumar P, Tiwari B, Belwal S, Saxena S, Abbas H. What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review. Indian J Crit Care Med 2020;24(12):1251–1255.
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Affiliation(s)
- Sanjeev Arya
- Department of Critical Care, Max Super Specialty Hospital (Previously), Dehradun, India
| | - Prashant Kumar
- Department of Critical Care, Kailash Hospital, Noida, Uttar Pradesh, India
| | - Bhuwan Tiwari
- Department of Cardiology, Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow, Uttar Pradesh, India
| | - Shantanu Belwal
- Department of Critical Care, Max Super Specialty Hospital, Dehradun, India
| | - Sanjay Saxena
- Department of Critical Care, Max Super Specialty Hospital, Dehradun, India
| | - Haider Abbas
- Department of ER and Critical Care, King Georges Medical University, Lucknow, Uttar Pradesh, India
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Wu VCC, Chen TH, Wu M, Huang CH, Chen SW, Cheng CW, Lin YS, Chang PC, Hsieh MJ, Wang CY, Chang SH, Wang CL, Chu PH, Wu CS. Risk of cardiac arrhythmias in patients with chronic hepatitis B and C infections - A 13-year nationwide population-based study. J Cardiol 2019; 74:333-338. [PMID: 30982681 DOI: 10.1016/j.jjcc.2019.03.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/06/2019] [Accepted: 03/14/2019] [Indexed: 11/17/2022]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with higher risk of cardiovascular events than chronic hepatitis B virus (HBV). We aimed to investigate whether there is higher risk of arrhythmia in HCV infection. METHODS Electronic medical records from National Health Institute Research Database during 2000-2012 were retrieved for patients with HBV or HCV. Patients with missing information, aged <18 years, diagnosed with HBV or HCV before year 2000, concomitant HBV and HCV, coagulopathy or organ transplant, history of arrhythmia, device implantation, congenital heart disease, rheumatic heart disease, hypertrophic cardiomyopathy, thyroid disease, alcohol or drug abuse, valvular heart disease, or follow-up <6 months were excluded. Primary outcomes were cardiac arrhythmias and all-cause mortality. RESULTS After 1:1 propensity score matching, 5480 patients with HBV and 5480 patients with HCV were included for study. During a mean follow-up of 6.5 years, the risk of all-cause mortality was higher in the HCV patients than in HBV patients [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.16-1.58]. There was also a trend toward higher incidence of atrial fibrillation (HR 1.25, 95% 0.98-1.59, p=0.070) and a significantly higher incidence of sick sinus syndrome (HR 1.77, 95% CI 1.07-2.91) in HCV patients. In addition, among patients with all-cause mortality, arrhythmia death was significantly higher with chronic HCV infection. CONCLUSIONS In patients with chronic viral hepatitis, patients with HCV were associated with significantly increased risks of sick sinus syndrome, and all-cause mortality compared to patients with HBV.
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Affiliation(s)
- Victor Chien-Chia Wu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan.
| | - Tien-Hsing Chen
- Department of Cardiology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Michael Wu
- Division of Cardiovascular Medicine, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
| | - Chien-Hao Huang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Shao-Wei Chen
- Department of Cardiothoracic and Vascular Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Chun-Wen Cheng
- Department of Infectious Diseases, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Yu-Sheng Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Po-Cheng Chang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Ming-Jer Hsieh
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Chao-Yung Wang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Shang-Hung Chang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Chun-Li Wang
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Pao-Hsien Chu
- Division of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan
| | - Cheng-Shyong Wu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan
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Reichart D, Magnussen C, Zeller T, Blankenberg S. Dilated cardiomyopathy: from epidemiologic to genetic phenotypes: A translational review of current literature. J Intern Med 2019; 286:362-372. [PMID: 31132311 DOI: 10.1111/joim.12944] [Citation(s) in RCA: 132] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and, consecutively, contractile dysfunction. The causes of DCM are heterogeneous. DCM often results from myocarditis, exposure to alcohol, drugs or other toxins and metabolic or endocrine disturbances. In about 35% of patients, genetic mutations can be identified that usually involve genes responsible for cytoskeletal, sarcomere and nuclear envelope proteins. Due to its heterogeneity, a detailed diagnostic work-up is necessary to identify the specific underlying cause and exclude other conditions with phenotype overlap. Patients with DCM show typical systolic heart failure symptoms, but, with progress of the disease, diastolic dysfunction is present as well. Depending on the underlying pathology, DCM patients also become apparent through arrhythmias, thromboembolic events or cardiogenic shock. Disease progression and prognosis are mostly driven by disease severity and reverse remodelling within the heart. The worst prognosis is seen in patients with lowest ejection fractions or severe diastolic dysfunction, leading to terminal heart failure with subsequent need for left ventricular assist device implantation or heart transplantation. Guideline-based heart failure medication and device therapy reduces the frequency of heart failure hospitalizations and improves survival.
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Affiliation(s)
- D Reichart
- From the, University Heart Center Hamburg, Hamburg, Germany
| | - C Magnussen
- From the, University Heart Center Hamburg, Hamburg, Germany
| | - T Zeller
- From the, University Heart Center Hamburg, Hamburg, Germany
| | - S Blankenberg
- From the, University Heart Center Hamburg, Hamburg, Germany
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Musialik J, Kolonko A, Kwiecień K, Owczarek AJ, Więcek A. Effectiveness and safety of sofosbuvir-based therapy against chronic hepatitis C infection after successful kidney transplantation. Transpl Infect Dis 2019; 21:e13090. [PMID: 30972854 DOI: 10.1111/tid.13090] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 03/15/2019] [Accepted: 03/31/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs), including sofosbuvir (SOF), are recommended for treatment of chronic hepatitis C virus (HCV) infection. However, few studies have investigated the effectiveness and safety of new DAAs in kidney transplant recipients (KTRs). OBJECTIVES To assess the effectiveness and safety of SOF-based therapy in stable KTRs. PATIENTS AND METHODS Forty KTRs were treated with SOF-based regimens. Rapid, end-therapeutic, and sustained virologic responses were assessed, as was liver stiffness by elastometry. Safety was monitored by measuring the estimated glomerular filtration rate (eGFR), blood hemoglobin (Hb) concentration, proteinuria, and blood trough levels of calcineurin inhibitors (CNIs). Other side effects were also recorded. RESULTS The effectiveness of DAAs was 100% at all time points. The therapy did not significantly influence eGFR or proteinuria, but significantly decreased mean blood Hb levels (13.5 ± 2.0 vs 11.6 ± 1.9, respectively, P < 0.001), which required a dose reduction or cessation of ribavirin (RBV) in 50% of patients. A profound, significant decrease in initial CNI concentrations was also observed during treatment in the majority of patients within the first month of therapy. CONCLUSIONS In this cohort of KTRs, the new SOF-based therapies were characterized by 100% effectiveness and good safety profiles. However, in patients co-treated with RBV, close blood Hb monitoring and early RBV dose reduction are necessary. In the majority of KTRs, antiviral therapy leads to a substantial and early decrease in CNIs levels, thus frequent measurement of CNI levels is necessary during SOF-based therapy.
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Affiliation(s)
- Joanna Musialik
- Department of Nephrology, Transplantation and Internal Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Aureliusz Kolonko
- Department of Nephrology, Transplantation and Internal Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Kwiecień
- Department of Nephrology, Transplantation and Internal Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Aleksander J Owczarek
- Department of Statistics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Andrzej Więcek
- Department of Nephrology, Transplantation and Internal Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
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Effects of Hepatitis C Virus Antibody-Positivity on Cardiac Function and Long-Term Prognosis in Patients With Adult Congenital Heart Disease. Am J Cardiol 2018; 122:1965-1971. [PMID: 30442226 DOI: 10.1016/j.amjcard.2018.08.045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/17/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023]
Abstract
It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction <50% was significantly higher in the HCV antibody-positive group compared with the HCV antibody-negative group (17 vs 5.4%, p = 0.014). During a mean follow-up period of 10.1 years (interquartile range 6 to 14 years), the CEP was noted in 51 patients. Kaplan-Meier analysis showed the HCV antibody-positive group had significantly poor event-free survival than the HCV antibody-negative group (log-rank, p = 0.002). In contrast, HCV ribonucleic acid-positivity was not a significant predictor of the CEP in the HCV antibody-positive group (log-rank, p = 0.442). Furthermore, the HCV antibody-positivity was significantly associated with the CEP in both univariable and multivariable Cox regression models (hazard ratio 2.37, 95% confident interval 1.32 to 4.15, p = 0.005 and 1.96, 1.06 to 3.63, p = 0.032, respectively). In conclusion, these results suggest that more attention should be paid to HCV antibody-positivity in the management of ACHD patients.
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14
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Strizhakov LA, Karpov SY, Fomin VV, Lopatkina TN, Tanashchuk EL, Taranova MV. [Myocardial injury associated with chronic hepatitis C: Clinical types and pathogenetic components]. TERAPEVT ARKH 2018. [PMID: 28635920 DOI: 10.17116/terarkh2016884105-111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Heart injury is one of the extrahepatic manifestations of chronic hepatitis C (CHC). The paper gives Russian and foreign authors' data on a relationship between CHC and myocardial injury. It discusses different pathogenetic components (the direct effect of the virus, immunological components), through which hepatitis C virus can induce myocarditis and cardiomyopathies in patients with CHC.
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Affiliation(s)
- L A Strizhakov
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
| | - S Yu Karpov
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
| | - V V Fomin
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
| | - T N Lopatkina
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
| | - E L Tanashchuk
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
| | - M V Taranova
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia
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De Luca G, Cavalli G, Campochiaro C, Tresoldi M, Dagna L. Myocarditis: An Interleukin-1-Mediated Disease? Front Immunol 2018; 9:1335. [PMID: 29951067 PMCID: PMC6008311 DOI: 10.3389/fimmu.2018.01335] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/29/2018] [Indexed: 12/20/2022] Open
Affiliation(s)
- Giacomo De Luca
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Giulio Cavalli
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.,Department of Medicine, Radboud University Medical Center, Nijmegen, Netherlands
| | - Corrado Campochiaro
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Moreno Tresoldi
- Unit of General Medicine and Advanced Care, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy
| | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
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16
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Cacoub P, Nahon P, Layese R, Blaise L, Desbois AC, Bourcier V, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Lédinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Calès P, Péron JM, Alric L, Bourlière M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grangé JD, Attali P, Bacq Y, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Capron D, Thiefin G, Zucman D, Di Martino V, Bagnis CI, Ziol M, Sutton A, Letouze E, Roudot-Thoraval F, Audureau E. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients. Am Heart J 2018; 198:4-17. [PMID: 29653647 DOI: 10.1016/j.ahj.2017.10.024] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 10/29/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. METHODS Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. RESULTS Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001). CONCLUSIONS In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Richard Layese
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | | | - Anne Claire Desbois
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | | | - Carole Cagnot
- Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENCH)
| | | | | | - Stanislas Pol
- Université Paris Descartes, APHP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1223 et USM20, Institut Pasteur, Paris, France
| | | | | | - Denis Ouzan
- Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var
| | | | | | - Albert Tran
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, France and University Hospital of Nice, Digestive Centre, Nice, France
| | | | | | - Ghassan Riachi
- Hôpital Charles-Nicolle, Service d'Hépato-gastro-entérologie, Rouen
| | - Paul Calès
- CHU d'Angers, Service d'Hépatologie, Angers
| | | | - Laurent Alric
- Service de Médecine Interne-Pôle Digestif CHU Toulouse, UMR 152, IRD, Toulouse 3 University
| | | | | | | | - Armand Abergel
- Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand
| | | | - Ariane Mallat
- AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil
| | | | - Pierre Attali
- AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif
| | - Yannick Bacq
- Hôpital Trousseau, Unité d'Hépatologie, CHRU de Tours
| | - Claire Wartelle
- Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence
| | - Thông Dao
- Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen
| | - Dominique Thabut
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris
| | | | | | | | | | | | | | | | - Corinne Isnard Bagnis
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Nephrology, Paris, France
| | - Marianne Ziol
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris; AP-HP, Hôpital Jean Verdier, Service d'Anatomopathologie, Bondy; CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027
| | - Angela Sutton
- CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027; AP-HP, Hôpital Jean Verdier, Service de Biochimie, Bondy
| | - Eric Letouze
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Françoise Roudot-Thoraval
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | - Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
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17
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Vassalle C, Petta S, Pepe A, Craxi A, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with cardiovascular disease. Antivir Ther 2018; 23:35-46. [PMID: 30451152 DOI: 10.3851/imp3248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.
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Affiliation(s)
- Cristina Vassalle
- Laboratory Medicine Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessia Pepe
- MRI Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Antonio Craxi
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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18
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Babiker A, Jeudy J, Kligerman S, Khambaty M, Shah A, Bagchi S. Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J Clin Transl Hepatol 2017; 5:343-362. [PMID: 29226101 PMCID: PMC5719192 DOI: 10.14218/jcth.2017.00021] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/15/2017] [Accepted: 07/27/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.
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Affiliation(s)
| | - Jean Jeudy
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Seth Kligerman
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Miriam Khambaty
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Anoop Shah
- Division of Cardiology, University of Edinburgh, Little France, Edinburgh
| | - Shashwatee Bagchi
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
- *Correspondence to: Shashwatee Bagchi, Division of Infectious Diseases, University of Maryland School of Medicine, 725 West Lombard Street, N359, Baltimore, MD 21201, USA. Tel: +1-410-706-4606, Fax: +1-410-706-3243, E-mail:
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19
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Wang JF, Yang Y, Wang G, Min J, Sullivan MF, Ping P, Xiao YF, Morgan JP. Embryonic Stem Cells Attenuate Viral Myocarditis in Murine Model. Cell Transplant 2017. [DOI: 10.3727/000000002783985233] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
We used mice to test our hypothesis that in response to viral invasion, stem cells may migrate into the heart and attenuate the effect of viral myocarditis. Male BALB/c mice were divided into three groups: mouse embryonic stem (ES) cell control, encephalomyocarditis virus (EMCV), and EMCV + ES cells. After administration of ES cells via tail vein, mice were immediately inoculated with EMCV. Mice were sacrificed at different days after EMCV inoculation. Mortality was recorded. Inflammatory cell infiltration and necrosis (major pathological changes of viral myocarditis) were evaluated by hematoxylin-eosin staining. ES cell migration and differentiation were identified by immunofluorescence. The survival rate in the EMCV + ES cell group (80%) was significantly increased (p < 0.05) over the EMCV-alone group (64%). Also, the incidence of inflammatory cell infiltration and myocardial lesions was lower in the EMCV + ES cell mice. Furthermore, the result of green fluorescent protein (GFP) and a-actinin analysis indicated that ES cells migrated into the heart and differentiated into myocytes after virus inoculation. In conclusion, ES cells significantly increased the survival of viral myocarditis mice and also decreased the necrosis and infiltration of inflammatory cells. These results demonstrated the ability of stem cells to mitigate the effects of viral infection on the heart and illustrated their potential therapeutic application to other mammalian species, including humans.
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Affiliation(s)
- Ju-Feng Wang
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
| | - Yingke Yang
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
| | - Guangwu Wang
- Cardiology Division, Department of Medicine, University of Louisville, Kentucky, KY 40202
| | - Jiangyong Min
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
| | - Matthew F. Sullivan
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
| | - Peipei Ping
- Cardiology Division, Department of Medicine, University of Louisville, Kentucky, KY 40202
| | - Yong-Fu Xiao
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
| | - James P. Morgan
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
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20
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21
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Domont F, Cacoub P. Chronic hepatitis C virus infection, a new cardiovascular risk factor? Liver Int 2016; 36:621-7. [PMID: 26763484 DOI: 10.1111/liv.13064] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 12/31/2015] [Indexed: 12/13/2022]
Abstract
Among the large scope of extrahepatic manifestations related to hepatitis C virus (HCV) infection, many studies recently evaluated the frequency and characteristics of cardiovascular involvement. To assess the current published data on HCV infection and cardiovascular diseases. Published studies on cardiovascular disease, i.e. cerebrovascular accident and ischaemic heart disease in subjects with HCV infection were analysed from literature databases. Subjects with HCV chronic infection have an increased prevalence of carotid atherosclerosis and increased intima-media thickness compared to healthy controls or those with hepatitis B or non-alcoholic steatohepatitis. Active chronic HCV infection appears as an independent risk factor for ischaemic cerebrovascular accidents. Active chronic HCV infection is associated with increased risk of ischaemic heart disease. In some studies, successful interferon-based therapy showed a beneficial impact on the cardiovascular risk. The risk of major cardiovascular events is higher in patients with HCV infection compared to controls, independent of the severity of the liver disease or the common cardiovascular risk factors. The beneficial impact of interferon-based therapy needs to be confirmed with new direct antiviral interferon-free agents in prospective studies with extended follow-up.
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Affiliation(s)
- Fanny Domont
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.,INSERM, UMR-S 959, Paris, France.,CNRS, FRE3632, Paris, France
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22
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Ngu PJ, Butler M, Pham A, Roberts SK, Taylor AJ. Cardiac remodelling identified by cardiovascular magnetic resonance in patients with hepatitis C infection and liver disease. Int J Cardiovasc Imaging 2015; 32:629-36. [PMID: 26667447 DOI: 10.1007/s10554-015-0824-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 12/07/2015] [Indexed: 01/06/2023]
Abstract
Chronic cardiac dysfunction in patients with chronic liver disease (CLD) in the absence of alcohol consumption or other cardiac disease is well described. Whilst functional and morphological features of this condition remain unclear, diastolic dysfunction has been implicated by echocardiography. We aimed to evaluate myocardial structure, function and tissue composition with cardiac magnetic resonance (CMR) imaging in patients with hepatitis C and histological evidence of liver disease on biopsy. Contrast-enhanced CMR imaging for morphological, functional and tissue characterization was performed on 16 patients with CLD and 21 healthy controls. Cardiac structure and function was assessed with standard cine imaging, with Late Gadolinium Enhancement (LGE) and myocardial T1 mapping (pre- and post-contrast) performed to evaluate regional and diffuse myocardial fibrosis respectively. Compared to controls, patients with CLD demonstrated lower left ventricular end-diastolic volume (LVEDV) (138 ± 36 vs. 167 ± 44 mL, p < 0.05), reduced stroke volume (88 ± 20 vs. 109 ± 29 mL, p = 0.016), lower post-contrast myocardial T1 time and higher Partition Coefficient consistent with diffuse myocardial fibrosis (466 ± 78 vs. 545 ± 134 ms and 0.247 ± 0.110 vs. 0.123 ± 0.057 %, p < 0.05 for both). There were no differences in other cardiac parameters including left ventricular mass and ejection fraction (p = NS for all comparisons). No patients in either group had evidence of LGE. Compared to controls, patients with hepatitis C and histological evidence liver involvement have lower LVEDV, SV and increased diffuse myocardial fibrosis, all of which are associated with diastolic dysfunction. LVEF and LV mass were preserved. This may explain in part previous functional observations made by echocardiography.
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Affiliation(s)
- Phillip J Ngu
- Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.,Baker IDI Heart and Diabetes Institute, Heart Centre, Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia
| | - Michelle Butler
- Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.,Baker IDI Heart and Diabetes Institute, Heart Centre, Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia
| | - Alan Pham
- Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Hospital, Melbourne, Australia
| | - Andrew J Taylor
- Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia. .,Baker IDI Heart and Diabetes Institute, Heart Centre, Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia.
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Increased Circulating Advanced Oxidation Protein Products and High-Sensitive Troponin T in Cirrhotic Patients with Chronic Hepatitis C: A Preliminary Report. BIOMED RESEARCH INTERNATIONAL 2015; 2015:786570. [PMID: 26665009 PMCID: PMC4668303 DOI: 10.1155/2015/786570] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 10/29/2015] [Accepted: 11/04/2015] [Indexed: 12/16/2022]
Abstract
Aim. To investigate the relationship between advanced oxidation protein products (AOPPs) and myocardial injury by comparing the selected biomarker for detecting myocardial injury [high-sensitive troponin T (hs-TnT)] in patients with chronic HCV infection. Methods and Results. Eighty-eight patients with cirrhosis and 40 healthy control subjects were enrolled in the study. Circulating levels of AOPPs-albumin (the ratio of AOPPs to albumin content), hs-TnT, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were assessed. Compared with healthy controls, the cirrhotic patients with chronic HCV infection had higher levels of AOPPs-albumin, which were associated with increased hs-TnT. When the presence of ascites was considered, the plasma levels of AOPPs-albumin were higher, as well as TNF-α. AOPPs-albumin positively correlated with hs-TnT level in all cirrhotic patients with chronic HCV infection and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high AOPPs-albumin levels and elevated hs-TnT levels. Conclusion. The simultaneous monitoring of plasma AOPPs and hs-TnT can be helpful for the alterations in myocardial function control in cirrhotic patients with chronic HCV infection.
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Anderson RD, Thompson A, Burns AT. Pulmonary arterial hypertension associated with the use of interferon therapy for chronic hepatitis C infection complicated by extrinsic left main coronary artery compression. Intern Med J 2015; 44:1027-30. [PMID: 25302721 DOI: 10.1111/imj.12554] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 03/11/2014] [Indexed: 11/26/2022]
Abstract
Interferon-alpha treatment is a rare cause of pulmonary arterial hypertension (PAH). We report a case of a 43-year-old man treated for chronic hepatitis C infection complicated by decompensated right heart failure diagnosed with PAH and external coronary artery compression secondary to a dilated pulmonary trunk. The novel complication of extrinsic coronary artery compression should be considered in PAH patients presenting with chest pain or acute coronary syndrome. Establishing a diagnosis has clinical value as pulmonary vasodilator therapy may improve symptoms.
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Affiliation(s)
- R D Anderson
- Department of Cardiology, St Vincent's Hospital, Melbourne, Victoria, Australia
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25
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Mozos I. Arrhythmia risk in liver cirrhosis. World J Hepatol 2015; 7:662-672. [PMID: 25866603 PMCID: PMC4388994 DOI: 10.4254/wjh.v7.i4.662] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 12/04/2014] [Accepted: 01/19/2015] [Indexed: 02/06/2023] Open
Abstract
Interactions between the functioning of the heart and the liver have been described, with heart diseases affecting the liver, liver diseases affecting the heart, and conditions that simultaneously affect both. The heart is one of the most adversely affected organs in patients with liver cirrhosis. For example, arrhythmias and electrocardiographic changes are observed in patients with liver cirrhosis. The risk for arrhythmia is influenced by factors such as cirrhotic cardiomyopathy, cardiac ion channel remodeling, electrolyte imbalances, impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT interval-prolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions.
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Mangini S, Higuchi MDL, Kawakami JT, Reis MM, Ikegami RN, Palomino SAP, Pomerantzeff PMA, Fiorelli AI, Marcondes-Braga FG, Bacal F, Ferreira SMA, Issa VS, Souza GEC, Chizzola PR, Bocchi EA. Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies. Int J Cardiol 2014; 178:55-62. [PMID: 25442238 DOI: 10.1016/j.ijcard.2014.10.133] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 10/21/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). OBJECTIVES The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. METHODS From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. RESULTS There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. CONCLUSIONS The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies.
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Affiliation(s)
- Sandrigo Mangini
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
| | - Maria de Lourdes Higuchi
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Joyce Tiyeko Kawakami
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Marcia Martins Reis
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Renata Nishiyama Ikegami
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | | | | | - Alfredo Inácio Fiorelli
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | | | - Fernando Bacal
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | | | - Victor Sarli Issa
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | | | - Paulo Roberto Chizzola
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
| | - Edimar Alcides Bocchi
- Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
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Abstract
Dilated cardiomyopathy is characterized by dilatation of the left or right ventricle, or both ventricles. The degree of myocardial dysfunction is not attributable to abnormal loading conditions. The infectious-immune theory has long been hypothesized to explain the pathogenesis of many etiologically unrecognized dilated cardiomyopathies. Inflammations followed by immune reactions, which may be excessive, in the myocardium, evoked by external triggers such as viral infections and/or autoimmune antibodies, continue insidiously, and lead to the process of cardiac remodeling with ventricular dilatation and systolic dysfunction. This ultimately results in dilated cardiomyopathy. Hepatitis C virus-associated heart diseases are good examples of cardiac lesions definitely induced by viral infections in humans that progress to a chronic stage through complicated immune mechanisms. Therapeutic strategies for myocarditis and dilated cardiomyopathy have been obtained through analyses of the acute, subacute, and chronic phases of experimental viral myocarditis in mice. The appropriate modulation of excessive immune reactions during myocarditis, rather than their complete elimination, appears to be a key option in the prevention and treatment of dilated cardiomyopathy. The clinical application of an NF-κB decoy and immune adsorption of IgG3 cardiac autoantibodies have been used as immunomodulating therapies and may provide novel approaches for the treatment of refractory patients with dilated cardiomyopathy. Conventional therapeutic agents for chronic heart failure such as β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists in particular should be re-evaluated on the basis of their anti-inflammatory properties in the treatment of dilated cardiomyopathy.
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28
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Abo-Haded HM, Barakat TS, Hafez MM. Myocardial performance in children with autoimmune hepatitis: Doppler tissue imaging study. Eur J Pediatr 2013; 172:1511-9. [PMID: 23812510 DOI: 10.1007/s00431-013-2073-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Accepted: 06/11/2013] [Indexed: 01/09/2023]
Abstract
Autoimmune hepatitis (AIH) is a member of autoimmune diseases family which can increase risk of cardiovascular morbidity and mortality. This study aimed to assess subclinical impact of AIH on global myocardial performance in affected children using Doppler tissue imaging (DTI) and to correlate it with total serum immunoglobulin-G (IgG). Thirty children with AIH (mean age = 12.67 ± 2.9 years) was included as the study group and 20 age- and sex-matched healthy children (mean age = 11.93 ± 2.66 years) as the control group. Conventional two-dimensional echocardiography was performed to both groups and DTI were used to determine right ventricular (RV) and left ventricular (LV) Tei indexes. Total serum IgG levels at initial diagnosis of AIH were correlated to the cardiac functions of AIH patients. RV and LV Tei indexes were significantly higher in AIH group (mean ± SD: 0.46 ± 0.088 vs. 0.26 ± 0.01, P < 0.0001 and 0.45 ± 0.086 vs. 0.31 ± 0.02, P < 0.0001, respectively). Also, total IgG concentrations were correlated positively with the LV Tei index (r = 0.69, P < 0.0001) and with the RV Tei index (r = 0.61, P < 0.0003) and correlated negatively with the mitral systolic (Sm) velocity (r = -0.76, P < 0.0001) and with tricuspid systolic (Sm) velocity (r = -0.66, P < 0.0001). On the other hand, fractional shortening did not correlate with serum IgG concentrations (r = -0.04, P = 0.821). In conclusion, the DTI technique appears to be more sensitive than conventional echocardiography in the early detection of myocardial dysfunction in AIH children.
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MESH Headings
- Adolescent
- Biomarkers/blood
- Case-Control Studies
- Child
- Cross-Sectional Studies
- Echocardiography, Doppler, Pulsed
- Female
- Hepatitis, Autoimmune/blood
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/diagnostic imaging
- Hepatitis, Autoimmune/immunology
- Humans
- Immunoglobulin G/blood
- Male
- Ventricular Dysfunction, Left/diagnostic imaging
- Ventricular Dysfunction, Left/etiology
- Ventricular Dysfunction, Right/diagnostic imaging
- Ventricular Dysfunction, Right/etiology
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Affiliation(s)
- Hany M Abo-Haded
- Pediatric Cardiology Unit, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt,
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29
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Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013; 34:2636-48, 2648a-2648d. [PMID: 23824828 DOI: 10.1093/eurheartj/eht210] [Citation(s) in RCA: 2232] [Impact Index Per Article: 186.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
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Affiliation(s)
- Alida L P Caforio
- Division of Cardiology, Department of Cardiological Thoracic and Vascular Sciences, University of Padua, Padova, Italy.
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30
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Abstract
We have developed murine models of viral myocarditis induced by encephalomyocarditis (EMC) virus in which severe myocarditis, congestive heart failure and dilated cardiomyopathy occur in high incidence. From these models, we have learned the natural history and pathogenesis and assessed not only new diagnostic methods but also therapeutic and preventive interventions. Autoantibodies against cardiac troponin I appeared in spontaneously developing autoimmune myocarditis in PD-1 deficient mice, who lack the T-cell receptor costimulatory molecule PD-1. The passive transfer of this antibody induced myocardial dysfunction. Later, this autoantibody was found in patients with myocarditis. Mast cell deficiency had beneficial effects in the viral myocarditis model, and anti-allergic agents prevented viral myocarditis. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blocker and an aldosterone receptor antagonist improved viral myocarditis, suggesting that the renin-angiotension-aldosterone system may play an important role in the pathogenesis of viral myocarditis. Differential modulation of cytokine production was seen with various calcium channel blockers, and some calcium channel blocker improved viral myocarditis. Viral infection could lead to increased synthesis of immunoglobulin light chains (FLC). Serum levels of FLC were increased in myocarditis, and exogenously given FLC inhibited viral replication and improved myocarditis. We suggest that a strategy of drug development specifically addressing inflammation in myocarditis may provide increased benefit in terms of target organ damage.
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31
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Okada K, Furusyo N, Ogawa E, Ikezaki H, Ihara T, Hayashi T, Kainuma M, Murata M, Hayashi J. Association between chronic hepatitis C virus infection and high levels of circulating N-terminal pro-brain natriuretic peptide. Endocrine 2013; 43:200-5. [PMID: 22581254 DOI: 10.1007/s12020-012-9688-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2011] [Accepted: 04/25/2012] [Indexed: 10/28/2022]
Abstract
The association between HCV infection and myocardial disorders remains unclear. This study aimed to assess whether or not HCV infection influences myocardial dysfunction by the use of NT-proBNP, a sensitive marker of myocardial dysfunction. A total of 198 participants [99 patients with chronic HCV infection (aged 46-68 years) and 99 anti-HCV-negative sex and age matched controls] were examined. Serum HCV-RNA level and HCV genotype were tested and liver biopsy was done only for the patient group. The NT-proBNP concentration of the HCV patients (mean 71.6 ± 79.1 pg/ml; median 46.0 pg/ml, range 5.0-400.0) was significantly higher than that of the controls (mean 39.8 ± 24.4 pg/ml; median 35.8 pg/ml, range 7.0-108.0) (P < 0.05). 20.0 % of the HCV patients and 0.6 % of the controls had high NT-proBNP (higher than 125 pg/ml; the single cut off point for patients under 75 years of age) (P < 0.05). Stepwise multiple regression analysis revealed that chronic HCV infection was independently correlated with NT-proBNP level after adjustment for parameters that might influence NT-proBNP (P = 0.005). Our data suggest that chronic HCV infection is associated with increased NT-proBNP, indicating that chronic HCV infection might induce myocardial dysfunction.
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Affiliation(s)
- Kyoko Okada
- Department of General Internal Medicine, Kyushu University Hospital, Maidashi, Fukuoka, 812-8582, Japan.
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32
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Demir M, Demir C. Effect of hepatitis B virus infection on right and left ventricular functions. Med Sci Monit 2013; 18:CR587-91. [PMID: 22936196 PMCID: PMC3560655 DOI: 10.12659/msm.883356] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND In this study we examined right and left ventricular systolic functions in hepatitis B virus (HBV) patients. MATERIAL/METHODS The study included 50 HBsAg-positive patients (mean age; 33±13 years) and 50 other persons (mean age; 28±11 years) as a control group. Transthoracic echocardiography was performed in all the participants. Right and left ventricle systolic parameters were compared between these 2 groups. RESULTS In the group of the patients with HBsAg positivity, the right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE) and RV myocardial systolic velocity (St) values were lower than in the control group (33±11 vs. 52±13%, p=0.001; 14.6±1.1 vs. 22.2±2.4 mm, p<0.001; 8.6±1.2 vs. 15.8±2.3 cm/s, p<0,001, respectively); the right atrium (RA) and RV diameters were higher than in controls (5.1±1.2 vs. 3.7±0.5 cm, p<0.001; 4.9±0.8 vs. 3.4±0.5 cm p<0.001, respectively); and systolic pulmonary artery pressure was higher than in control (39.3±9.5 vs. 22±8.4 mmHg, p<0.001). CONCLUSIONS The findings showed that HBV infection may be associated with right ventricular systolic dysfunction and pulmonary hypertension.
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Affiliation(s)
- Mehmet Demir
- Department of Cardiology, Bursa Yuksek Ihtisas Education and Research Hospital, Bursa, Turkey.
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33
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Myocardial injury in patients with chronic hepatitis C infection. J Hepatol 2013; 58:11-5. [PMID: 22889957 DOI: 10.1016/j.jhep.2012.07.045] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Revised: 07/13/2012] [Accepted: 07/31/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy. METHODS In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C. RESULTS An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of the chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer, and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, SS improved at the initial disappearance of HCV RNA, but it worsened with the reappearance of HCV RNA. SS in non-viral responders did not change with IFN therapy. CONCLUSIONS Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication with IFN therapy.
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34
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Caforio ALP, Marcolongo R, Jahns R, Fu M, Felix SB, Iliceto S. Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and management. Heart Fail Rev 2012; 18:715-32. [DOI: 10.1007/s10741-012-9364-5] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
Myocarditis is an underdiagnosed cause of acute heart failure, sudden death, and chronic dilated cardiomyopathy. In developed countries, viral infections commonly cause myocarditis; however, in the developing world, rheumatic carditis, Trypanosoma cruzi, and bacterial infections such as diphtheria still contribute to the global burden of the disease. The short-term prognosis of acute myocarditis is usually good, but varies widely by cause. Those patients who initially recover might develop recurrent dilated cardiomyopathy and heart failure, sometimes years later. Because myocarditis presents with non-specific symptoms including chest pain, dyspnoea, and palpitations, it often mimics more common disorders such as coronary artery disease. In some patients, cardiac MRI and endomyocardial biopsy can help identify myocarditis, predict risk of cardiovascular events, and guide treatment. Finding effective therapies has been challenging because the pathogenesis of chronic dilated cardiomyopathy after viral myocarditis is complex and determined by host and viral genetics as well as environmental factors. Findings from recent clinical trials suggest that some patients with chronic inflammatory cardiomyopathy have a progressive clinical course despite standard medical care and might improve with a short course of immunosuppression.
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Affiliation(s)
- Sandeep Sagar
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
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36
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Antonelli A, Ferri C, Ferrari S, Di Domenicantonio A, Mancusi C, Marchi S, De Bortoli N, Metelli M, Bruschi F, Fallahi P. Hepatitis C is Associated with High Levels of Circulating N-Terminal Pro-Brain Natriuretic Peptide and Interleukin-6. EUR J INFLAMM 2012. [DOI: 10.1177/1721727x1201000117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
To our knowledge, no study has evaluated N-terminal pro-brain natriuretic peptide (NTproBNP) together with interleukin-6 (IL-6) and interferon (IFN)-gamma serum levels in a large series of patients with hepatitis C virus (HCV) as possible markers of cardiac dysfunction. NTproBNP and IL-6 serum levels were valued in 55 HCV-patients, and in 55 sex- and age-matched controls. HCV-patients showed significantly higher mean NTproBNP and IL-6 levels than controls ( P = 0.001); no significant difference was observed for IFN-gamma. By defining high NTproBNP level as a value higher than 300 pg/mL (that is used to rule out heart failure in patients under 75 years of age), 12% (6/49) of HCV-patients and 0 of controls had NTproBNP (χ2; P = 0.012). In conclusion, this study demonstrates high levels of circulating NTproBNP and IL-6 in HCV-patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction. Further prospective studies quantifying symptoms and correlating these with echocardiography parameters are needed to confirm this association.
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Affiliation(s)
- A. Antonelli
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - C. Ferri
- Department of Internal Medicine, Rheumatology Unit, University of Modena & Reggio E. School of Medicine, Modena, Italy
| | - S.M. Ferrari
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - A. Di Domenicantonio
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - C. Mancusi
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - S. Marchi
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - N. De Bortoli
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - M.R. Metelli
- Department of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa, Italy
| | - F. Bruschi
- Department of Experimental Pathology and B.M.I.E., University of Pisa School of Medicine, Pisa, Italy
| | - P. Fallahi
- Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy
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Effect of hepatitis C virus infection on the left ventricular systolic and diastolic functions. South Med J 2011; 104:543-6. [PMID: 21886060 DOI: 10.1097/smj.0b013e31822462e2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Hepatitis secondary to infection with the hepatitis C virus (HCV) is one of the most common causes of viral hepatitis worldwide. Multiple extrahepatic manifestations of HCV infection have been recognized. Dilated and hypertrophic cardiomyopathy associated with HCV infection have been recently described in the literature; however, the effect of HCV infection on the left ventricular systolic and diastolic functions is unknown. Therefore, in this study we aimed to examine left ventricular systolic and diastolic functions in HCV patients. METHODS AND RESULTS The study included 50 anti-HCV positive patients and 50 persons for control groups. We performed transthorasic echocardiography and P-wave analysis on all participants. We compared left ventricle diastolic parameters, left ventricle ejection fraction, and P-wave dispersion (Pd) between these two groups. In the group with anti-HCV positivity, the ratio of E/A was found to be lower (1.2 ± 0.7 and 1.37 ± 0.6, P = 0.003); the ratio of E/Em was found to be higher (7.6 ± 1.51 and 6.8 ± 1.72, P = 0.0001). Maximum P-wave duration (Pmax) and Pd were higher in the patient group (99.3 ± 8 and 82.4 ± 7.8, P = 0.004; 44.1 ± 0.9 and 25.3 ± 1.5, P = 0.001). No other statistically significant difference was found between the two groups with regard to the left ventricle systolic and diastolic parameters. CONCLUSION Our findings show that HCV infection may be associated with left ventricular systolic and diastolic dysfunction and cardiac arrhythmias.
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Durante-Mangoni E, Iossa D, Pinto D, De Vincentiis L, Ragone E, Utili R. Safety and efficacy of peginterferon alpha plus ribavirin in patients with chronic hepatitis C and coexisting heart disease. Dig Liver Dis 2011; 43:411-5. [PMID: 21310673 DOI: 10.1016/j.dld.2010.12.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Revised: 12/18/2010] [Accepted: 12/30/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic hepatitis C patients with coexisting heart disease are often denied antiviral treatment due to safety concerns. However, this is not evidence-based. AIMS To evaluate safety and efficacy of pegylated interferon and ribavirin in chronic hepatitis C patients with heart disease. METHODS Patients with overt heart disease (ischaemic heart disease, prior mechanical heart valve replacement, chronic arrhythmias and cardiomyopathy) and chronic hepatitis C were treated with standard pegylated interferon/ribavirin doses for standard duration. Cardiovascular safety was monitored by electrocardiography, echocardiography and measurement of troponin and B-type natriuretic peptide. RESULTS Twenty-three patients (65.2% male, median age 57 years, 47.8% genotype 1) were treated. Three patients (13%) suspended treatment prematurely; 52% obtained sustained virological response, 39% relapsed, 9% were non-responders. No serious adverse event was observed. Post-treatment clinical examination, electrocardiography and echocardiography did not show any sign of progression of the pre-existing heart disease. CONCLUSIONS Treatment with pegylated interferon/ribavirin may be safely offered to carefully selected chronic hepatitis C patients with coexisting, clinically significant heart disease. In these patients, the outcome of antiviral treatment overlaps that observed in other patient subgroups.
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Antonelli A, Ferri C, Ferrari SM, Marchi S, De Bortoli N, Sansonno D, Chiavacci C, Ferrannini E, Fallahi P. N-terminal pro-brain natriuretic peptide and tumor necrosis factor-alpha both are increased in patients with Hepatitis C. J Interferon Cytokine Res 2010; 30:359-63. [PMID: 20187770 DOI: 10.1089/jir.2009.0059] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Many patients with hepatitis C chronic infection (HCV+ patients) experience symptoms (fatigue, dyspnea) not proportional to the liver involvement and resemble symptoms of heart failure (HF). To our knowledge, no study evaluated at the same time serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor alpha (TNF-alpha) in HCV+ patients. Circulating NT-proBNP and TNF-alpha were assayed in 60 HCV+ patients, and in 60 sex- and age-matched controls. HCV+ patients showed significantly higher mean NT-proBNP and TNF-alpha levels than controls (P < 0.003). By defining high NT-proBNP level as a value higher than 125 pg/mL (the single cutoff point for outpatients under 75 years of age), 28% of HCV+ and 7% controls had high NT-proBNP (chi-square; P < 0.002). With a cutoff point of 900 pg/mL (that should be used for ruling in HF in patients age 50-75; such as the patients in our study), 3% HCV+ and 0 controls had high NT-proBNP. In conclusion, the study demonstrates high levels of circulating NT-proBNP and TNF-alpha in HCV+ patients. The increase of NT-proBNP may indicate the presence of a subclinical cardiac dysfunction. Further prospective studies quantifying symptoms and correlating these with echocardiographic parameters are needed to confirm this association.
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Affiliation(s)
- Alessandro Antonelli
- Department of Internal Medicine, University of Pisa School of Medicine , Pisa, Italy.
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40
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Kanazawa H. Relationship between hepatitis C virus infection and pulmonary disorders: potential mechanisms of interaction. Expert Rev Clin Immunol 2010; 2:801-10. [PMID: 20477634 DOI: 10.1586/1744666x.2.5.801] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Recently, an increasing number of reports have suggested that chronic hepatitis C virus (HCV) infection is associated with pulmonary disorders. The effects of HCV on the lung may present as worsening of lung function and impaired responses to therapy in patients with chronic obstructive pulmonary disease and asthma. Moreover, chronic HCV infection may be associated with the pathogenesis of interstitial lung disease. It is believed that chronic HCV infection may contribute to the immune responses modulating the pathogenic processes underlying pulmonary disorders and, therefore, may lead to a wide spectrum of clinical presentations. Potential candidates for a role in these immune responses are the CD8(+) T lymphocytes and inflammatory cytokines. In this review, the effects of HCV on the lung and the potential mechanisms of interaction between chronic HCV infection and pulmonary disorders will be discussed.
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Affiliation(s)
- Hiroshi Kanazawa
- Osaka City University, Department of Respiratory Medicine, Graduate School of Medicine, 1-4-3, Asahi-machi, Abenoku, Osaka 545-8585, Japan.
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Matsumori A, Shimada M, Obata T. Leukocytes are the major target of hepatitis C virus infection: Possible mechanism of multiorgan involvement including the heart. ACTA ACUST UNITED AC 2010. [DOI: 10.1016/j.cvdpc.2010.04.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Dhillon S, Kaker A, Dosanjh A, Japra D, Vanthiel DH. Irreversible pulmonary hypertension associated with the use of interferon alpha for chronic hepatitis C. Dig Dis Sci 2010; 55:1785-90. [PMID: 20411421 PMCID: PMC2882564 DOI: 10.1007/s10620-010-1220-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2009] [Accepted: 03/23/2010] [Indexed: 02/06/2023]
Abstract
The interferons are a complex group of virally induced proteins produced by activated macrophages and lymphocytes, which have become the mainstay of therapy for hepatitis C infection. Sustained viral response (SVR) rates in noncirrhotic patients vary from 40-80% with interferon-based therapy. This, along with transplantation, has drastically changed the course of hepatitis C virus (HCV) infection over the last two decades. Numerous side effects associated with interferon therapy have been reported. These range from transient flu-like symptoms to serious effects such as cardiac arrhythmias, cardiomyopathy, renal and liver failure, polyneuropathy, and myelosuppression. Pulmonary side effects including pneumonitis, pulmonary fibrosis, and reversible pulmonary hypertension have been reported. Herein, we present four cases in which irreversible pulmonary hypertension was diagnosed after prolonged treatment with interferon alpha. In each case, other causes of pulmonary hypertension were systematically eliminated. Pulmonary artery hypertension, which may be irreversible, should be considered in patients being treated with interferon alpha who present with exertional dyspnea and do not have a readily identifiable inflammatory or thromboembolic cause.
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Affiliation(s)
- Sonu Dhillon
- Department of Medicine, Rush University Medical Center, Ste. 158 Professional Building, Chicago, IL 60612, USA.
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Calabrese F, Carturan E, Thiene G. Cardiac infections: focus on molecular diagnosis. Cardiovasc Pathol 2010; 19:171-82. [DOI: 10.1016/j.carpath.2009.09.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2009] [Revised: 09/24/2009] [Accepted: 09/28/2009] [Indexed: 01/09/2023] Open
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Charniot JC, Vignat N, Monsuez JJ, Kidouche R, Avramova B, Artigou JY, Albertini JP. Cardiogenic shock associated with reversible dilated cardiomyopathy during therapy with regular doses of venlafaxine. Am J Emerg Med 2010; 28:256.e1-5. [DOI: 10.1016/j.ajem.2009.05.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2009] [Revised: 05/17/2009] [Accepted: 05/17/2009] [Indexed: 10/19/2022] Open
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Minemura M, Tajiri K, Shimizu Y. Systemic abnormalities in liver disease. World J Gastroenterol 2009; 15:2960-2974. [PMID: 19554648 PMCID: PMC2702103 DOI: 10.3748/wjg.15.2960] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2009] [Revised: 05/23/2009] [Accepted: 05/30/2009] [Indexed: 02/06/2023] Open
Abstract
Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.
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Matsumori A. Global alert and response network for hepatitis C virus-derived heart diseases: A call to action. ACTA ACUST UNITED AC 2009. [DOI: 10.1016/j.cvdpc.2009.02.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Tsui JI, Whooley MA, Monto A, Seal K, Tien PC, Shlipak M. Association of hepatitis C virus seropositivity with inflammatory markers and heart failure in persons with coronary heart disease: data from the Heart and Soul study. J Card Fail 2009; 15:451-6. [PMID: 19477406 PMCID: PMC2782758 DOI: 10.1016/j.cardfail.2008.12.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2008] [Revised: 10/22/2008] [Accepted: 12/04/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND How hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown. METHODS AND RESULTS Among a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-alpha) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P < .01), but higher levels of TNF-alpha (7.1 vs. 4.8; P < .01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000p-y (P < .01), CV events 62 vs. 40 (P=.13), and heart failure 76 vs. 29 (P < .01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR=2.13; 95% CI: 1.19-3.80). CONCLUSIONS In this cohort with CHD, HCV seropositive participants had higher rates of death, CV events, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.
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Affiliation(s)
- Judith I Tsui
- Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine/Boston Medical Center, Boston, MA 02118, USA.
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Abstract
Myocardial inflammation of cardiac muscle is caused by intramyocardial infiltration of immunological competent cells. Etiologically, the relevant factors are the direct or indirect influence of infectious pathogens, toxic, chemical or physical agents, allergic-hyperergic reactions and myocardial inflammatory events in the context of systemic diseases. Clinically significant infections include cardiotropic viruses, which are capable of causing acute or chronic damage to the myocardium under certain conditions. The wide variety of etiologies in inflammatory cardiomyopathy and its heterogeneous clinical presentations have impeded patients identification and consensus on the most appropriate diagnostic criteria and specific therapeutic strategies. Although the Dallas criteria have standardized the histological definition of active myocarditis, the recognition of true etiologies of acute and chronic stages of inflammatory cardiomyopathies require additional and more sensitive markers of tissue inflammation and molecular biological identification of responsible infectious agents. Actually, only biopsy-based diagnosis and characterization of patients allow identification of patients who may get benefit from specific immunosuppressive or anti-viral treatment strategies.
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Affiliation(s)
- H P Schultheiss
- Medizinische Klinik II, Kardiologie und Pneumonologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Deutschland.
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Shichi D, Matsumori A, Naruse TK, Inoko H, Kimura A. HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy. Int J Immunogenet 2008; 35:37-43. [PMID: 18186799 DOI: 10.1111/j.1744-313x.2007.00733.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by hypertrophy and diastolic dysfunction of cardiac ventricles. It is suggested that one possible aetiology of HCM is the hepatitis C virus (HCV) infection, but molecular mechanisms underlying development of HCV-associated HCM (HCV-HCM) remains unknown. Because the human leucocyte antigen (HLA) molecule is involved in the control of progression/suppression of viral infection, extensive HLA allelic diversity may modulate the post-infectious course of HCV and pathogenesis of HCV-HCM. Here we undertook a case-control study with 38 patients with HCV-HCM and 132 unrelated healthy controls to reveal the potential impact of polymorphisms in seven classical and two non-classical HLA genes on the pathogenesis of HCV-HCM. It was found that DPB1*0401 and DPB1*0901 were significantly associated with increased risk to HCV-HCM in dominant model (P < 0.028, OR = 3.94, 95% confidence interval (CI) = 1.19, 13.02) and in recessive model (P < 0.007, OR = 9.85, 95% CI = 1.83, 53.04), respectively. The disparity in the gene-dose effect by two susceptible DPB1 alleles may be attributable to the difference between the susceptible (36 A and 55 A) and resistant (8L, 9F, 11G, 57E and 76M) residue-combination consisting of DPbeta anchor pocket for antigenic peptide-binding. These results implied that the HLA-DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of HCM among the HCV-infected individuals.
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Affiliation(s)
- D Shichi
- Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
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Ueno A, Murasaki K, Hagiwara N, Kasanuki H. Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyopathy. Heart Vessels 2007; 22:316-21. [PMID: 17879023 DOI: 10.1007/s00380-007-0977-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2006] [Accepted: 01/26/2007] [Indexed: 02/07/2023]
Abstract
Inflammatory and immunological mechanisms are implicated in the development of idiopathic dilated cardiomyopathy (DCM). Since activated T lymphocytes express surface HLA-DR antigens, an increased level of these cells in the circulation could indicated an ongoing immune response. While the role of activated T lymphocytes in experimental myocarditis has been elucidated, the contribution of T lymphocyte activation in clinical DCM remains unclear. We therefore examined the role of T-cell activation in peripheral blood samples obtained from 10 patients with DCM (mean age, 49 +/- 12 years) and from 10 age-matched healthy controls. Citrated whole blood was mixed with fluorescein isothiocyanate- or phycoerythrin-conjugated specific monoclonal antibodies and analyzed using a fluorescence-activated cell sorter (FACS). The ratio (%) of histocompatibility leukocyte antigen (HLA)-DR positive cells in the FACS gated lymphocyte population was significantly higher in DCM patients than in controls (7.9% +/- 5.3% vs 2.0% +/- 0.9%; P < 0.01). The expression of CD40L on T cells determined as mean fluorescence intensity (MFI) was also significantly higher in DCM patients than in controls (3.6 +/- 2.1 vs 1.8 +/- 0.4 MFI; P < 0.05). Furthermore, the ratios of T cells expressing HLA-DR and serum brain natriuretic peptide (BNP) levels closely correlated (P = 0.0008). We showed that HLA-DR on peripheral T cells significantly correlated with serum BNP levels and that high CD40L expression on T cells was concomitant with increased BNP levels (P < 0.05). Therefore the magnitude of T-cell expression, such as increased expression of HLA-DR and CD40L, contributes to myocardial dysfunction in DCM.
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Affiliation(s)
- Atsuko Ueno
- Department of Cardiology, Tokyo Women's Medical University, Tokyo 162-8666, Japan
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