日本循環器学会他：2023 年改訂版 心筋炎の診断・治療に関するガイドライン．https://www.j-circ.or.jp/cms/wp-content/uploads/2023/03/JCS2023_nagai.pdf.
日本循環器学会他：循環器病の診断と治療に関するガイドライン（2008 年度合同研究班報告）急性および慢性心筋炎の診断・治療に関するガイドライン（2009年改訂版）．www.j-circ.or.jp/guideline/pdf/JCS2009_izumi_d.pdf.
Ville Kytö, Antti Saraste, Liisa-Maria Voipio-Pulkki, Pekka Saukko
Incidence of fatal myocarditis: a population-based study in Finland.
Am J Epidemiol. 2007 Mar 1;165(5):570-4. doi: 10.1093/aje/kwk076. Epub 2007 Jan 19.
Abstract/Text
To study the incidence of fatal myocarditis in the general population, the authors retrospectively collected all death certificates recording myocarditis as the underlying cause of death in Finland in 1970-1998. The incidence of myocarditis and its proportion of all deaths were calculated from 141.4 million person-years and 1.35 million deaths. Myocarditis was recorded as the underlying cause of death in 639 cases. Thus, its death certificate-based incidence was 0.46 (95% confidence interval (CI): 0.43, 0.49) per 100,000 person-years, and it caused 0.47 (95% CI: 0.44, 0.51) of 1,000 deaths. The incidence of 0.51 (95% CI: 0.46, 0.56) in males was higher than the incidence of 0.42 (95% CI: 0.37, 0.47) in females, the odds ratio being 1.34 (95% CI: 1.15, 1.58) (p < 0.001). The proportion of deaths caused by myocarditis was highest (up to six of 1,000 deaths) in children and adults aged less than 45 years. Because previous histopathologic reanalysis showed that only 32% of cases fulfilled the Dallas criteria, the authors estimated the incidence of histopathologically certain fatal myocarditis to be 0.15 (95% CI: 0.13, 0.17) per 100,000. The death certificate-based incidence of fatal myocarditis was found to be 0.46 per 100,000, and the histopathologically corrected incidence was 0.15 per 100,000.
日本小児循環器学会学術委員会：小児期急性・劇症心筋炎の診断と治療の指針. 日本小児循環器学会雑誌 2006;.22 (4):514-524.
日本循環器学会編：急性および慢性心筋炎の診断・治療に関するガイドライン. Circ J 2004; 68( Suppl. Ⅳ): 1231-1263.
Neil E Bowles, Jiyuan Ni, Debra L Kearney, Matthias Pauschinger, Heinz-Peter Schultheiss, Robert McCarthy, Joshua Hare, J Timothy Bricker, Karla R Bowles, Jeffrey A Towbin
Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults.
J Am Coll Cardiol. 2003 Aug 6;42(3):466-72.
Abstract/Text
OBJECTIVES: The purpose of this study was to analyze cardiac tissue and blood for viral genomes using polymerase chain reaction (PCR) to define the common viral etiologies of myocarditis by age group.
BACKGROUND: Enteroviruses are considered the most common cause of myocarditis at all ages. Diagnosis relies on viral cultures, serology, and cardiac histology, which lack sensitivity, as well as PCR. However, in many cases enteroviruses are not detected.
METHODS: Cardiac samples were obtained for PCR analysis from patients with myocarditis (n = 624) and dilated cardiomyopathy (DCM) (n = 149). Patients were analyzed by age group, including neonates (n = 116), infants (n = 191), toddlers (n = 87), children (n = 110), adolescents (n = 92), and adults (n = 177). After nucleic acids had been extracted from an endomyocardial biopsy, an explant, or autopsy samples, PCR and reverse transcription PCR were performed to detect the genomic sequences of enterovirus, adenovirus, cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), parvovirus, respiratory syncytial virus (RSV), and influenza A virus.
RESULTS: Viral genome was amplified (adenovirus = 142, enterovirus = 85, CMV = 18, parvovirus = 6, influenza A = 5, HSV = 5, EBV = 3, RSV = 1) from 239 (38%) of the 624 samples from myocarditis patients, including 26 patient samples in which dual infection was found. Virus was detected in 30 (20%) of 149 DCM patient samples; only adenovirus (n = 18) and enterovirus (n = 12) were detected.
CONCLUSIONS: Polymerase chain reaction identified adenovirus as the most common virus in the myocardium of children and adults with myocarditis and DCM. Although enteroviruses are also found in these patients, they appear to be a less common cause of myocarditis than adenovirus.
Naoyoshi Aoyama, Tohru Izumi, Katsuhiko Hiramori, Mitsuaki Isobe, Masatoshi Kawana, Michiaki Hiroe, Hitoshi Hishida, Yasushi Kitaura, Tsutomu Imaizumi, Japanese Investigators of Fulminant Myocarditis
National survey of fulminant myocarditis in Japan: therapeutic guidelines and long-term prognosis of using percutaneous cardiopulmonary support for fulminant myocarditis (special report from a scientific committee).
Circ J. 2002 Feb;66(2):133-44.
Abstract/Text
Although fulminant myocarditis is known as a fatal disease, patients have been able to recover and return to normal life with the help of mechanical cardiopulmonary support. However, therapeutic guidelines for using percutaneous cardiopulmonary support (PCPS) for fulminant myocarditis have not been established, and the clinical course and long-term prognosis of such patients are still controversial issues. The present national survey considered the current situation of patients as the basis for proposing therapeutic guidelines. Thirty of 52 patients (57.7%) survived and returned to social life. Important factors concerning the prognosis were the severity and grade of cardiac and renal dysfunction, the adjusted support flow rate to enable recovery from circulatory failure, and prevention of circulatory disturbances of the legs and multiple organ failure directly associated with PCPS. With regard to the long-term prognosis of patients treated with PCPS, the readmission rate was 10%, the exacerbation rate was 3.3%, and mortality was 10% during the average follow-up period of 962 days. Optimal management of the mechanical cardiopulmonary support and curative treatment for the myocarditis further improve the outcome of this disease.
Ishikawa Y. Cardiac Magnetic Resonance Imaging, Pediatric Cardiology and Cardiac Surgery 32(4): 291‒306 (2016).
Elisabet Witsø, Gustavo Palacios, Ondrej Cinek, Lars C Stene, Bjørn Grinde, Diana Janowitz, W Ian Lipkin, Kjersti S Rønningen
High prevalence of human enterovirus a infections in natural circulation of human enteroviruses.
J Clin Microbiol. 2006 Nov;44(11):4095-100. doi: 10.1128/JCM.00653-06. Epub 2006 Aug 30.
Abstract/Text
Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in serial monthly collections from healthy Norwegian infants. A total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. The samples were analyzed for HEV nucleic acid by real-time PCR. Fifty-eight children (51.3%) had HEV infections. One hundred forty-five positive samples were typed directly by nucleotide sequencing of the VP1 region. HEV-A was detected most frequently, with an overall prevalence of 6.8%. HEV-B was present in 4.8% of the samples and HEV-C in only 0.2% of the samples. No poliovirus or HEV-D group viruses were detected. Twenty-two different serotypes were detected in the study period: the most common were EV71 (14.5%), CAV6 (10.5%), CAV4 (8.9%), E18 (8.9%), and CBV3 (7.3%). These findings suggest that the prevalence of HEV infections in general, and HEV-A infections in particular, has been underestimated in epidemiological studies based on virus culture.
A B Martin, S Webber, F J Fricker, R Jaffe, G Demmler, D Kearney, Y H Zhang, J Bodurtha, B Gelb, J Ni
Acute myocarditis. Rapid diagnosis by PCR in children.
Circulation. 1994 Jul;90(1):330-9.
Abstract/Text
BACKGROUND: The diagnosis of viral myocarditis remains difficult and generally depends on clinical and histological criteria. Viral cultures and serology are often unrewarding, with low yields. The purpose of this study was to analyze the usefulness of polymerase chain reaction (PCR) in the rapid diagnosis of acute myocarditis in children.
METHODS AND RESULTS: PCR was used to analyze 38 myocardial tissue samples from 34 patients with suspected acute viral myocarditis and 17 control patients with congenital heart disease (14) or hypertrophic cardiomyopathy (3). Myocardial samples were obtained at the time of right ventricular biopsy (13 samples), from explanted hearts (18 samples) at transplantation, and from cardiac autopsy specimens (24 samples) and were evaluated for the presence of enterovirus, cytomegalovirus (CMV), adenovirus, and herpes simplex virus (HSV) using PCR primers designed to consensus and unique sequences of these viral genomes. Blood also was obtained at the time of biopsy (11) or transplant (18). In 26 of 38 myocardial samples (68%), viral genome was detected by PCR (15 adenoviral, 8 enteroviral, 2 HSV, 1 CMV), whereas all control myocardial samples and blood samples were negative. Four patients had positive viral cultures, and these matched the PCR findings. Disagreement with histopathology occurred in 13 of 26 PCR-positive specimens, usually associated with adenovirus.
CONCLUSIONS: PCR offers a rapid, sensitive diagnostic method for myocardial viral infection. While enterovirus is an important etiological agent, adenovirus was more prevalent in this series and should be evaluated when etiology is sought. PCR used in conjunction with standard endomyocardial biopsy appears to enhance the likelihood of detecting viral genome in the myocardium of patients with clinical evidence of myocarditis.
Bowles NE, Towbin JA. Childhood myocarditis and dilated cardiomyopathy, In Myocarditis - From bench to bedside. Ed by Cooper LT, Human Press, New Jersey 2002: 559-588.
Fiorella Calabrese, Emanuela Rigo, Ornella Milanesi, Giovanni M Boffa, Annalisa Angelini, Marialuisa Valente, Gaetano Thiene
Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications.
Diagn Mol Pathol. 2002 Dec;11(4):212-21.
Abstract/Text
Myocarditis is the most common cause of heart failure in children. We investigated viral etiology of myocarditis/dilated cardiomyopathy (DCM) in children and correlated molecular findings with pathologic and clinical data. Polymerase chain reaction (PCR) or reverse transcription (RT)-PCR were used to analyze 59 endomyocardial biopsies from 48 consecutive young (<18 yrs) patients (pts) with clinical and histologic diagnosis of myocarditis and DCM, employing primers designed to amplify specific sequences of various DNA and RNA viruses. Nucleic acids were successfully extracted in 41 pts and viral genomes were found in 20 (49%): 12 out of 26 pts (46%) with myocarditis, 6 out of 13 (46%) pts with DCM, and both patients with endocardial fibroelastosis. Enteroviruses were more common in DCM (72%), whereas adenoviruses and enteroviruses shared the same rate (36%) in myocarditis. The mumps virus genome was detected in the two pts with endocardial fibroelastosis. More diffuse inflammatory infiltrates and myocyte damage as well as more impaired left ventricular end diastolic volume and shortening fraction were noted in viral positive cases. PCR positive pts had a worse outcome, resulting in transplantation or death. Three out of 8 pts with viral myocarditis who underwent cardiac transplantation had recurrent PCR-proven graft viral infection. Viral myocarditis/DCM appeared to be a more severe disease than nonviral forms. Enteroviruses were more common in DCM, whereas adenoviruses were as frequent as enteroviruses in myocarditis. Persistence of viral infection was associated with disease deterioration. Viral myocarditis relapsed after transplantation.
J B O'Connell, R E Henkin, J A Robinson, R Subramanian, P J Scanlon, R M Gunnar
Gallium-67 imaging in patients with dilated cardiomyopathy and biopsy-proven myocarditis.
Circulation. 1984 Jul;70(1):58-62.
Abstract/Text
Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammation-sensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans (p less than .001). The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis.
A J Morguet, D L Munz, H Kreuzer, D Emrich
Scintigraphic detection of inflammatory heart disease.
Eur J Nucl Med. 1994 Jul;21(7):666-74.
Abstract/Text
Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated.
D M McNamara, W D Rosenblum, K M Janosko, M K Trost, F S Villaneuva, A J Demetris, S Murali, A M Feldman
Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy.
Circulation. 1997 Jun 3;95(11):2476-8.
Abstract/Text
BACKGROUND: Although an autoimmune pathogenesis has been postulated for dilated cardiomyopathy, immunosuppressive therapy has not been shown to be effective in clinical trials. Immune modulatory therapy with immune globulin is an effective therapy for Kawasaki disease in children, and recent data suggest that it improves ventricular function in children with new-onset dilated cardiomyopathies. The role of immune globulin therapy in adults with this disorder has not previously been evaluated.
METHODS AND RESULTS: Ten patients were treated with high-dose intravenous immune globulin infusions (2 g/kg). All were hospitalized with NYHA class III to IV heart failure, left ventricular ejection fraction (LVEF) < 0.40, and symptoms for < 6 months at the time of presentation. One patient died before the completion of therapy. The remaining 9 were discharged, and LVEF was reassessed 12 months after therapy. LVEF improved from 0.24 +/- 0.02 (mean +/- SEM) at baseline to 0.41 +/- 0.04 at follow-up (P = .003). All 9 patients improved functionally to NYHA class I to II, and there have been no subsequent hospitalizations for heart failure during the course of follow-up.
CONCLUSIONS: In this series of patients with new-onset dilated cardiomyopathy treated with high-dose immune globulin, LVEF improved 17 EF units. The effectiveness of intravenous immune globulin therapy in this disorder should be evaluated in a randomized, multicenter trial.
