The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention
Introduction: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. Results: 756 heart fai...
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| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/2/299 |
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| author | Ahmed Elsanhoury Uwe Kühl Bruno Stautner Oliver Klein Alexander Krannich Daniel Morris Monika Willner Ewa Jankowska Karin Klingel Sophie Van Linthout Carsten Tschöpe |
| author_facet | Ahmed Elsanhoury Uwe Kühl Bruno Stautner Oliver Klein Alexander Krannich Daniel Morris Monika Willner Ewa Jankowska Karin Klingel Sophie Van Linthout Carsten Tschöpe |
| author_sort | Ahmed Elsanhoury |
| collection | DOAJ |
| description | Introduction: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. Results: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (<i>n</i> = 79) of which 62% (<i>n</i> = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (<i>n</i> = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3–12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. Conclusion: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials. |
| first_indexed | 2024-03-09T20:52:43Z |
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| id | doaj.art-8ab3d618fc8146588d6e2f372f6c6947 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T20:52:43Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8ab3d618fc8146588d6e2f372f6c69472023-11-23T22:30:41ZengMDPI AGViruses1999-49152022-01-0114229910.3390/v14020299The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive InterventionAhmed Elsanhoury0Uwe Kühl1Bruno Stautner2Oliver Klein3Alexander Krannich4Daniel Morris5Monika Willner6Ewa Jankowska7Karin Klingel8Sophie Van Linthout9Carsten Tschöpe10Berlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyBerlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyBerlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyBerlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyExperimental and Clinical Research Center (ECRC), Charité—Universitätsmedizin Berlin, 13125 Berlin, GermanyDepartment Internal Medicine and Cardiology, Charité—University Medicine Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment Internal Medicine and Cardiology, Charité—University Medicine Berlin, Campus Virchow Klinikum, 13353 Berlin, GermanyInstitute of Heart Diseases, University Hospital Wroclaw, 50-556 Wroclaw, PolandCardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, 72076 Tübingen, GermanyBerlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyBerlin Institute of Health at Charite (BIH)-Universitätmedizin Berlin-BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, GermanyIntroduction: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. Results: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (<i>n</i> = 79) of which 62% (<i>n</i> = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (<i>n</i> = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3–12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. Conclusion: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.https://www.mdpi.com/1999-4915/14/2/299myocarditishuman herpesvirus 6immunosuppression |
| spellingShingle | Ahmed Elsanhoury Uwe Kühl Bruno Stautner Oliver Klein Alexander Krannich Daniel Morris Monika Willner Ewa Jankowska Karin Klingel Sophie Van Linthout Carsten Tschöpe The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention Viruses myocarditis human herpesvirus 6 immunosuppression |
| title | The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention |
| title_full | The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention |
| title_fullStr | The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention |
| title_full_unstemmed | The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention |
| title_short | The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention |
| title_sort | spontaneous course of human herpesvirus 6 dna associated myocarditis and the effect of immunosuppressive intervention |
| topic | myocarditis human herpesvirus 6 immunosuppression |
| url | https://www.mdpi.com/1999-4915/14/2/299 |
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