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      Long-Term Prognosis of Suspected Myocarditis and Cardiomyopathy Associated with Viral Infection of the Myocardial Tissue: A Meta-Analysis of Cohort Studies

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      Author(s): 1 , 2 , 2 , 2 ,
      Publication date (Electronic):
      Journal: Cardiovascular Therapeutics
      Publisher: Hindawi

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          Abstract

          Aim

          Myocarditis and cardiomyopathy impose a substantial economic burden on society. Many studies have examined the effects of various predictors on the prognosis of these diseases, such as the left ventricular systolic function, the New York Heart Association glomerular filtration rate, the QT interval, and the presence of viruses. In the present study, we conducted a meta-analysis of cohort studies to investigate the significance of the presence of viruses in the myocardial tissue on the prognosis of these diseases.

          Methods

          The Embase, PubMed, and Cochrane library databases were searched for relevant literature that had been published between January 1, 1964 and August 14, 2018. The inclusion criteria were patients over 18 years of age, suspected myocarditis or dilated cardiomyopathy, accepted myocardial biopsy, and the detection of virus in the myocardial tissue.

          Results

          In total, 10 studies met the inclusion criteria. These studies included 1006 patients with suspected myocarditis or idiopathic heart disease for whom the primary endpoint was all-cause death, heart transplant, or re-hospitalization due to fatal arrhythmia and heart failure. There was no significant difference in the prognosis of virus-positive and virus-negative patients with myocarditis or dilated cardiomyopathy confirmed by endomyocardial biopsy (EMB) [hazard ratio (HR) = 1.40, 95% confidence interval (CI) = 0.93–2.12, P = 0.11]. However, virus-negative patients had a better prognosis following nonspecific treatment (HR = 1.40, 95% CI = 1.06–1.86, P = 0.02) and right ventricular biopsy (HR = 2.08, 95% CI = 1.07–4.04, P = 0.03).

          Conclusions

          The presence of a virus did not worsen the long-term prognosis of patients with suspected myocarditis or dilated cardiomyopathy. However, virus-positive patients who did not undergo specific treatment or who underwent right ventricular biopsy did have a worse prognosis. Thus, the early diagnosis of the presence of viral infection in the myocardium will improve the prognosis of patients.

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          Viral persistence in the myocardium is associated with progressive cardiac dysfunction.

          Uwe Kühl, Matthias Pauschinger, Bettina Seeberg … (2005)
          Cardiotropic viral infections have been suspected as one possible cause of myocarditis and dilated cardiomyopathy. Although adverse outcomes in dilated cardiomyopathy patients have been documented, the natural course of heart diseases caused by cardiotropic viruses is unknown. Consecutive patients (n=172) with biopsy-proven viral infection in endomyocardial biopsies (EMBs) were followed up by reanalysis of EMBs and hemodynamic measurements after a median period of 6.8 months (range, 5.4 to 11.9). Nested polymerase chain reaction (PCR) and reverse transcription-PCR were performed to analyze the genomic sequences. Myocardial inflammation was assessed by histology and immunohistology. At baseline, 32.6% of EMBs in the study group contained enteroviral (EV) RNA, 8.1% adenovirus (ADV) DNA, 36.6% parvovirus B19 (PVB19) DNA, and 10.5% human herpesvirus type 6 (HHV6) DNA. In 12.2% of the samples, dual infection with PVB19 and HHV6 was present. Follow-up analysis of EMBs by PCR documented spontaneous clearance of viral genomes in 36.2% (55/151) of all patients with single infections. Virus-specific clearance rates were 50% for EV, 35.7% for ADV, 22.2% for PVB19, and 44.4% for HHV6. In patients with dual infection with PVB19+ and HHV6(+)-, HHV6 was cleared in 42.8% (9/21), whereas PVB19 persisted in all 21 patients. Clearance of viral genomes was associated with a significant improvement in left ventricular ejection fraction (LVEF), improving from 50.2+/-19.1% to 58.1+/-15.9% (P<0.001). In contrast, LV function decreased in patients with persisting viral genomes (LVEF, 54.3+/-16.1% versus 51.4+/-16.1%, P<0.01). In this first biopsy-based analysis of the course of viral heart disease, we show that EV, ADV, PVB19, and HHV6 persistence detected in the myocardium of patients with LV dysfunction was associated with a progressive impairment of LVEF, whereas spontaneous viral elimination was associated with a significant improvement in LV function.
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            The global burden of myocarditis: part 1: a systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study.

            Leslie Cooper, Karen Sliwa, Andre Keren … (2014)
            Myocarditis contributes to the global burden of cardiovascular disease primarily through sudden death and dilated cardiomyopathy. A systematic approach to identify the cardiovascular mortality and major morbidity attributable to myocarditis has not been performed. A writing group convened by the GBD 2010 (Global Burden of Diseases, Injuries and Risk Factors) Study systematically reviewed the world's literature by a manual review of all titles since 1966 on myocarditis identified using Ovid Medline, development of a disease model, and provision of estimates when possible of the incidence, prevalence, risk of death, and major morbidity for the world regions. Accurate population-based estimates of myocarditis incidence and prevalence are not directly available in any world region. However, a model that quantitates the risk of acute death and chronic heart failure following myocarditis was derived from the published data. Using hospital dismissal data, the burden of myocarditis as a percentage of prevalent heart failure varied by age and region from approximately 0.5% to 4.0%. The novel combination of multiple data sources may provide an estimate of the years of life lost and years of life disabled from myocarditis. Pending the integration of these data sources, the burden of dilated cardiomyopathy and myocarditis were reported together in the 2010 GBD report. The 2013 GBD project may refine these estimates with the inclusion of more comprehensive payor databases and more precise case definitions.
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              Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.

              C Freeke, Guy P. Richardson, H J Why … (1994)
              Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue. We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value. These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.
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                Author and article information

                Contributors
                Huan-Ji Zhang:
                ORCID: https://orcid.org/0000-0003-2920-2928
                Journal
                Journal ID (nlm-ta): Cardiovasc Ther
                Journal ID (iso-abbrev): Cardiovasc Ther
                Journal ID (publisher-id): CDTP
                Title: Cardiovascular Therapeutics
                Publisher: Hindawi
                ISSN (Print): 1755-5914
                ISSN (Electronic): 1755-5922
                Publication date Collection: 2019
                Publication date (Electronic): 16 December 2019
                Volume: 2019
                Electronic Location Identifier: 9342792
                Affiliations
                1Graduate Department, Guangdong Medical University, Zhanjiang, China
                2Cardiovascular Center, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
                Author notes

                Academic Editor: Brian Tomlinson

                Author information
                https://orcid.org/0000-0003-2920-2928
                Article
                DOI: 10.1155/2019/9342792
                PMC ID: 6942786
                SO-VID: 70567c4b-7630-4809-a797-c7c9be09bbb9
                Copyright © Copyright © 2019 Wen-Hao Chen et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 May 2019
                Date accepted : 13 August 2019
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Cardiovascular Medicine
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine

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