今日の臨床サポート

心筋炎

著者: 山本博之1) 成田富里徳洲会病院 循環器内科

著者: 橋村一彦2) 阪和記念病院 心臓血管センター

監修: 伊藤浩 岡山大学循環器内科

著者校正/監修レビュー済:2021/12/01
参考ガイドライン:
  1. 日本循環器学会: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)
患者向け説明資料

概要・推奨   

  1. 急性心筋炎では劇症化の徴候に常に注意し、よいタイミングでの循環動態補助導入が望まれる。ほとんどのウイルス性心筋炎による劇症型心筋炎にはステロイド治療が無効であるが、好酸球性心筋炎のようにステロイド治療が著効する劇症型心筋炎もあることを常に念頭に置く必要がある(推奨度1)。
  1. 冠危険因子の低い胸痛の鑑別診断として、急性心筋炎の診断は常に念頭に置かなければならない。
  1. 心筋生検では採取部位や採取時期、標本の個数により結果が異なる。発症10日以内の時期で、3か所以上の部位からの採取が推奨される(推奨度1)。 
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
山本博之 : 特に申告事項無し[2021年]
橋村一彦 : 特に申告事項無し[2021年]
監修:伊藤浩 : 講演料(第一三共,興和,アストラゼネカ,小野,ノバルティスファーマ),研究費・助成金など(興和,Canon),奨学(奨励)寄付など(第一三共,田辺三菱,小野薬品,興和,Boston,武田,ベーリンガーインゲルハイム,持田,バイエル),企業などが提供する寄付講座(日本メドトロニック)[2021年]

改訂のポイント:
  1. 定期レビューを行った。
  1. ”好酸球性心筋炎における治療法とその適応評価まで”の項目を新規変更追記した。 

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 心筋炎とは、臨床的あるいは病理学的に心筋に炎症細胞浸潤が確認される炎症性心疾患である。炎症が心膜まで及ぶ場合は、心膜心筋炎と呼ばれる。
  1. 病因の多くはウイルスや細菌などの感染症であるが、薬物や放射線、膠原病や川崎病などの全身疾患に伴うものや特発性などさまざまである。組織学的にはリンパ球性(多くはウイルス感染)、巨細胞性、好酸球性、肉芽腫性に分類される。病型としては急性心筋炎、慢性心筋炎に分類される。急性心筋炎のなかで生命危機に至るものを、劇症型心筋炎と呼ぶ[1]
 
心筋炎の分類

心筋炎の分類は組織分類、病因分類、臨床病型分類の3種類からなる[1]。組織学的特徴から心筋炎はリンパ球性心筋炎、巨細胞性心筋炎、好酸球性心筋炎、肉芽腫性心筋炎に分類される。病因的にはほとんどがリンパ球性心筋炎はウイルス感染によるもので、巨細胞性心筋炎、好酸球性心筋炎、肉芽腫性心筋炎は心毒性物質・薬物アレルギー・自己免疫・全身性疾患などの合併症とみなされることが多い[2]。発病初期に心筋生検を行えば組織診断に基づいた治療計画を立てることができるが、実際には発病初期には心筋生検が困難である症例や正確な組織診断が難しい症例もある。発症様式により、心筋炎は急性心筋炎と慢性心筋炎に分けられる。急性心筋炎のなかで発病初期に心肺危機に陥るものを劇症型心筋炎と呼ぶ。慢性心筋炎には遷延性と不顕性の2型がある。
 
参考文献:
  1. 日本循環器学会他編: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)、p4 表2
  1. Aoyama N, Izumi T, Hiramori K, et al. 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; 66: 133-144.PubMed PMID:11999637.

 
  1. 心筋炎の正確な発症頻度は不明で、ばらつきが大きい。軽症例では見逃される例も多いと思われる。剖検例による検討では2~5%といわれている。
  1. 急性心筋炎は1~2週間で自然軽快し後遺症を残さない例が多いが、数時間で劇症化する例もあり原則として入院による治療が必要である。
問診・診察のポイント  
  1. 発熱、上気道感染、消化器症状、関節痛、筋肉痛などのウイルス感染の出現後、呼吸困難や胸痛、動悸、ときに失神などの様々な臨床症状が出現するため、ウイルスの先行感染の有無とその時期を問診することは、診断と病勢を推測するうえで重要である。

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文献 

著者: Matthias G Friedrich, Udo Sechtem, Jeanette Schulz-Menger, Godtfred Holmvang, Pauline Alakija, Leslie T Cooper, James A White, Hassan Abdel-Aty, Matthias Gutberlet, Sanjay Prasad, Anthony Aletras, Jean-Pierre Laissy, Ian Paterson, Neil G Filipchuk, Andreas Kumar, Matthias Pauschinger, Peter Liu, International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis
雑誌名: J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87. doi: 10.1016/j.jacc.2009.02.007.
Abstract/Text Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria").

PMID 19389557  J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87. doi: 10.・・・
著者: Ingrid Kindermann, Christine Barth, Felix Mahfoud, Christian Ukena, Matthias Lenski, Ali Yilmaz, Karin Klingel, Reinhard Kandolf, Udo Sechtem, Leslie T Cooper, Michael Böhm
雑誌名: J Am Coll Cardiol. 2012 Feb 28;59(9):779-92. doi: 10.1016/j.jacc.2011.09.074.
Abstract/Text Myocarditis is an inflammatory disease of the heart frequently resulting from viral infections and/or post-viral immune-mediated responses. It is one of the important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed on clinical presentation and noninvasive diagnostic methods such as cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic benefits of endomyocardial biopsy results have recently been demonstrated in several clinical trials. Although remarkable advances in diagnosis, understanding of pathophysiological mechanisms, and treatment of acute myocarditis were gained during the last years, no standard treatment strategies could be defined as yet, apart from standard heart failure therapy and physical rest. In severe cases, mechanical support or heart transplantation may become necessary. There is some evidence that immunosuppressive and immunomodulating therapy are effective for chronic, virus-negative inflammatory cardiomyopathy. Further investigations by controlled, randomized studies are needed to definitively determine their role in the treatment of myocarditis.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22361396  J Am Coll Cardiol. 2012 Feb 28;59(9):779-92. doi: 10.10・・・
著者: Hassan Abdel-Aty, Philipp Boyé, Anja Zagrosek, Ralf Wassmuth, Andreas Kumar, Daniel Messroghli, Petra Bock, Rainer Dietz, Matthias G Friedrich, Jeanette Schulz-Menger
雑誌名: J Am Coll Cardiol. 2005 Jun 7;45(11):1815-22. doi: 10.1016/j.jacc.2004.11.069.
Abstract/Text OBJECTIVES: The aim of this research was to identify the diagnostic performance of gadolinium-enhanced and T2-weighted cardiovascular magnetic resonance (CMR) in suspected acute myocarditis.
BACKGROUND: Acute myocarditis is difficult to diagnose; CMR provides various means to visualize myocardial inflammatory changes. A CMR approach with clear-cut diagnostic criteria would be desirable.
METHODS: We investigated 25 patients with suspected acute myocarditis (18 males, 44 +/- 17 years) and 23 healthy controls (13 males, 29 +/- 10 years). Cardiovascular magnetic resonance studies included the following sequences: 1) T2-weighted triple inversion recovery; 2) T1-weighted spin echo before and over 4 min after gadolinium injection; and 3) inversion recovery-gradient echo 10 min after gadolinium injection. Qualitative and quantitative image analysis was performed for: 1) focal and global T2 signal intensity (SI); 2) myocardial global relative enhancement (gRE); and 3) areas of late gadolinium enhancement (LGE).
RESULTS: Both global T2 SI and gRE were higher in patients than in controls (T2: 2.3 +/- 0.4 vs. 1.7 +/- 0.4; p < 0.0001, gRE: 6.8 +/- 4.0 vs. 3.7 +/- 2.3; p < 0.001). The sensitivity, specificity, and diagnostic accuracy for T2 (cutoff value of 1.9) were 84%, 74%, and 79%, respectively; gRE: (cutoff value of 4.0) 80%, 68%, and 74.5% respectively; LGE: 44%, 100%, and 71%, respectively. The best diagnostic performance was obtained when "any-two" of the three sequences were positive in the same patient yielding a 76% sensitivity, 95.5% specificity, and 85% diagnostic accuracy.
CONCLUSIONS: A combined CMR approach using T2-weighted imaging, early and late gadolinium enhancement, provides a high diagnostic accuracy and is a useful tool in the diagnosis and assessment of patients with suspected acute myocarditis.

PMID 15936612  J Am Coll Cardiol. 2005 Jun 7;45(11):1815-22. doi: 10.1・・・
著者: Anthony H Aletras, Peter Kellman, J Andrew Derbyshire, Andrew E Arai
雑誌名: Magn Reson Med. 2008 Feb;59(2):229-35. doi: 10.1002/mrm.21490.
Abstract/Text ACUT(2)E TSE-SSFP is a hybrid between steady state free precession (SSFP) and turbo spin echo (TSE) for bright-blood T2-weighted imaging with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) similar to dark-blood TSE. TSE-SSFP uses a segmented SSFP readout during diastole with 180 degrees pulses following a 90 degrees preparation. The 180 degrees refocusing pulses make TSE-SSFP similar to TSE but TSE-SSFP uses gradient moment nulling, whereas TSE uses gradient crushing. TSE-SSFP produced T2-weighted images with minimal T1 weighting. TSE-SSFP and TSE had similar SNR (155.9 +/- 6.0 vs 160.9 +/- 7.0; P = NS) for acute myocardial infarction (MI) and twice the SNR of T2-prepared SSFP (73.1 +/- 3.4, P < 0.001). TSE-SSFP and TSE had approximately double the CNR of T2-prepared SSFP for differentiating acute MI from normal myocardium. Imperfect blood suppression, present in all animals on some TSE images, was a problem eliminated by TSE-SSFP and T2-prepared SSFP.

(c) 2008 Wiley-Liss, Inc.
PMID 18228588  Magn Reson Med. 2008 Feb;59(2):229-35. doi: 10.1002/mrm・・・
著者: Heiko Mahrholdt, Anja Wagner, Claudia C Deluigi, Eva Kispert, Stefan Hager, Gabriel Meinhardt, Holger Vogelsberg, Peter Fritz, Juergen Dippon, C-Thomas Bock, Karin Klingel, Reinhard Kandolf, Udo Sechtem
雑誌名: Circulation. 2006 Oct 10;114(15):1581-90. doi: 10.1161/CIRCULATIONAHA.105.606509. Epub 2006 Oct 2.
Abstract/Text BACKGROUND: Enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6 (HHV6) are increasingly found in endomyocardial biopsy samples.
METHODS AND RESULTS: Consequently, our aim was to evaluate the prevalence and clinical presentation of cardiac PVB19 and/or HHV6 infection in a cohort of myocarditis patients and to follow its clinical course. In addition, we sought to demonstrate patterns of myocardial damage and to determine predictors for chronic heart failure. Our study design consisted of a cardiovascular magnetic resonance protocol as well as endomyocardial biopsies in the myocardial region affected as indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients were enrolled by clinical criteria. In the group of myocarditis patients (n=87), PVB19 (n=49), HHV6 (n=16), and combined PVB19/HHV6 infections (n=15) were detected most frequently. The remaining patients were diagnosed with healing myocarditis (n=15) or did not have myocarditis (n=26). Patients with PVB19 presented in a manner similar to that of myocardial infarction; most had typical subepicardial late gadolinium enhancement in the lateral wall and recovered within months. Conversely, patients with HHV6 and especially with HHV6/PVB19 myocarditis presented with new onset of heart failure, had septal late gadolinium enhancement, and frequently progressed toward chronic heart failure.
CONCLUSIONS: Our data indicate that PVB19 and HHV6 are the most important causes for viral myocarditis in Germany and that the clinical presentation is related to the type of virus. Furthermore, clinical presentation, type of virus, and pattern of myocardial damage are related to the clinical course.

PMID 17015795  Circulation. 2006 Oct 10;114(15):1581-90. doi: 10.1161/・・・
著者: Ismail Erden, Emine Cakcak Erden, Hakan Ozhan, Cengiz Basar
雑誌名: Cardiol J. 2011;18(5):552-5.
Abstract/Text The prevalence of myocardial involvement in influenza infection ranges from 0% to 11% depending on the diagnostic criteria used to define myocarditis. Whether such an association holds for the novel influenza A strain, pandemic-2009-H1N1, remains unknown. The clinical presentation of myocarditis varies and often mimics myocardial infarction. Although history, physical examination, laboratory data points, and electrocardiogram are helpful in distinguishing myocarditis from myocardial infarction, differential diagnosis can sometimes be difficult. Here, we present the first known report of acute myocarditis mimicking acute myocardial infarction associated with the pandemic influenza A virus (H1N1) infection.

PMID 21947992  Cardiol J. 2011;18(5):552-5.
著者: Naoyoshi Aoyama, Tohru Izumi, Katsuhiko Hiramori, Mitsuaki Isobe, Masatoshi Kawana, Michiaki Hiroe, Hitoshi Hishida, Yasushi Kitaura, Tsutomu Imaizumi, Japanese Investigators of Fulminant Myocarditis
雑誌名: 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.

PMID 11999637  Circ J. 2002 Feb;66(2):133-44.
著者: B Pinamonti, E Alberti, A Cigalotto, L Dreas, A Salvi, F Silvestri, F Camerini
雑誌名: Am J Cardiol. 1988 Aug 1;62(4):285-91.
Abstract/Text This study analyzes morphologic and functional alterations detected by M-mode and 2-dimensional echocardiography in 41 patients with histologically proven myocarditis and different clinical presentations: congestive heart failure (63%), atrioventricular block (17%), chest pain (15%) and supraventricular arrhythmias (5%). Left ventricular dysfunction was common (69%), particularly in patients with congestive heart failure (88%), often without or with minor cavity dilatation. Patients with atrioventricular block or chest pain had usually preserved ventricular function. Right ventricular dysfunction was present in 23%. Additional findings included asynergic ventricular areas (64%), left ventricular "hypertrophy" sometimes reversible (20%), hyperrefractile myocardial areas (23%), ventricular thrombi (15%) and "restrictive" ventricular filling (7%). It is concluded that echocardiographic features of myocarditis are polymorphous and nonspecific. The echocardiographic pattern can simulate alternatively dilated, hypertrophic, restrictive or "right" ventricular cardiomyopathy, as well as coronary artery disease. In an appropriate clinical context, echocardiography can be helpful in the diagnosis of myocarditis and in the selection of patients for endomyocardial biopsy.

PMID 3400607  Am J Cardiol. 1988 Aug 1;62(4):285-91.
著者: G M Felker, J P Boehmer, R H Hruban, G M Hutchins, E K Kasper, K L Baughman, J M Hare
雑誌名: J Am Coll Cardiol. 2000 Jul;36(1):227-32.
Abstract/Text OBJECTIVES: We sought to use echocardiography to assess the presentation and potential for recovery of left ventricular (LV) function of patients with fulminant myocarditis compared with those with acute myocarditis.
BACKGROUND: The clinical course of patients with myocarditis remains poorly defined. We have previously proposed a classification that provides prognostic information in myocarditis patients. Fulminant myocarditis causes a distinct onset of illness and severe hemodynamic compromise, whereas acute myocarditis has an indistinct presentation, less severe hemodynamic compromise and a greater likelihood of progression to dilated cardiomyopathy.
METHODS: Echocardiography was performed at presentation and at six months to test the hypothesis that fulminant (n = 11) or acute (n = 43) myocarditis could be distinguished morphologically.
RESULTS: Patients with both fulminant (fractional shortening 19 +/- 4%) and acute myocarditis (17 +/- 7%) had LV systolic dysfunction. Patients with fulminant myocarditis had near normal LV diastolic dimensions (5.3 +/- 0.9 cm) but increased septal thickness (1.2 +/- 0.2 cm) at presentation, while those with acute myocarditis had increased diastolic dimensions (6.1 +/- 0.8 cm, p < 0.01 vs. fulminant) but normal septal thickness (1.0 +/- 0.1 cm, p = 0.01 vs. fulminant). At six months, patients with fulminant myocarditis had dramatic improvement in fractional shortening (30 +/- 8%) compared with no improvement in patients with acute myocarditis (19 +/- 7%, p < 0.01 for interaction between time and type of myocarditis).
CONCLUSIONS: Fulminant myocarditis is distinguishable from acute myocarditis by echocardiography. Patients with fulminant myocarditis exhibit a substantial improvement in ventricular function at six months compared with those with acute myocarditis. Echocardiography has value in classifying patients with myocarditis and may provide prognostic information.

PMID 10898439  J Am Coll Cardiol. 2000 Jul;36(1):227-32.
著者: L A Wu, A C Lapeyre, L T Cooper
雑誌名: Mayo Clin Proc. 2001 Oct;76(10):1030-8. doi: 10.4065/76.10.1030.
Abstract/Text Dilated cardiomyopathy is a common cause of congestive heart failure. Despite a thorough cardiovascular evaluation, a specific cause is frequently not found, and the disorder then is considered idiopathic. Endomyocardial biopsy (EMB) may yield diagnostic and prognostic information in patients with idiopathic dilated cardiomyopathy; however, the yield of useful information with this procedure among patients with heart failure is low, and the risks of occasional cardiac perforation and death further limit its use. Recent publications in the field of myocarditis and cardiomyopathy have renewed interest in the use of EMB in select patients to diagnose specific and potentially treatable myocarditides; however, the role of EMB in the work-up of patients with dilated cardiomyopathy is not well defined. In this article, we discuss the risks and utility of EMB in the management of patients with dilated cardiomyopathy and specific myocarditides.

PMID 11605687  Mayo Clin Proc. 2001 Oct;76(10):1030-8. doi: 10.4065/76・・・
著者: Leslie T Cooper, Kenneth L Baughman, Arthur M Feldman, Andrea Frustaci, Mariell Jessup, Uwe Kuhl, Glenn N Levine, Jagat Narula, Randall C Starling, Jeffrey Towbin, Renu Virmani, American Heart Association, American College of Cardiology, European Society of Cardiology, Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology
雑誌名: J Am Coll Cardiol. 2007 Nov 6;50(19):1914-31. doi: 10.1016/j.jacc.2007.09.008.
Abstract/Text
PMID 17980265  J Am Coll Cardiol. 2007 Nov 6;50(19):1914-31. doi: 10.1・・・
著者: Juyup Han, Yongwhi Park, Hyunsang Lee, Hyunjae Kang, Hyungseop Kim, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung-Chull Chae, Jae-Eun Jun, Wee-Hyun Park
雑誌名: J Korean Med Sci. 2006 Dec;21(6):989-94.
Abstract/Text Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac pathologies. However, the routine use of EMBx has not gained widespread acceptance due to the possible complications related to the EMBx. Thus, not much information is available on the complications related to the EMBx. We prospectively evaluated 90 consecutive patients who underwent 2-D echocardiography guided transfemoral right ventricular EMBx at Kyungpook National University Hospital between March 2002 and November 2005 to determine the incidence, nature and subsequent management of complications related to EMBx. The clinical diagnoses before the EMBx were arrhythmogenic right ventricular dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis in 6 and miscellaneous in 2 patients. The overall major complication rate was 5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3), which was the most frequent complication, did not progress to cardiac tamponade requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular tachycardia occurred in 1 patient. New and persistent right bundle branch block occurred in another. Our findings suggest that 2-D echocardiography guided transfemoral right ventricular EMBx is a relatively safe procedure.

PMID 17179674  J Korean Med Sci. 2006 Dec;21(6):989-94.
著者: Shigeru Kato, Shin-Ichiro Morimoto, Shinya Hiramitsu, Akihisa Uemura, Masatsugu Ohtsuki, Yasuchika Kato, Kenji Miyagishima, Yukihiko Yoshida, Shuji Hashimoto, Hitoshi Hishida
雑誌名: Circ J. 2004 Aug;68(8):734-9.
Abstract/Text BACKGROUND: A fulminant course can be difficult to predict at the onset of acute myocarditis, so the aim of the present study was to identify the predictive clinical symptoms/signs or laboratory findings.
METHODS AND RESULTS: Thirty-nine patients with acute lymphocytic myocarditis, excluding 8 who manifested shock at admission, were studied. The fulminant group was defined as 12 patients who developed shock after admission, requiring intraaortic balloon pumping or percutaneous cardiopulmonary support, and the non-fulminant group comprised the 27 patients without shock. Various parameters at admission were compared between the 2 groups, together with multiple logistic regression analysis, excluding 6 patients with partially missing values. In the fulminant group, C-reactive protein (7.0 +/- 7.0 vs 2.3 +/- 2.2 mg/dl, p<0.01) and creatine kinase (1,147 +/- 876 vs 594 +/- 568 IU/L, p<0.05) concentrations were higher, intraventricular conduction disturbances were more frequent (9/12 vs 7/27 patients, p<0.01) and the left ventricular ejection fraction was lower (40.7 +/- 13.9 vs 50.1 +/- 10.6%, p<0.05) than in the non-fulminant group. In the multiple logistic regression analysis model with the presence/absence of a fulminant course considered as the independent variable, and C-reactive protein, creatine kinase, intraventricular conduction disturbances, and left ventricular ejection fraction as dependent variables, a high-risk group (expected proportion of fulminant course > or = 0.5) and a low-risk group (<0.5) could be differentiated. A fulminant course occurred in 9/13 (69%) patients in the high-risk group, but in only 2/20 (10%) patients in the low risk group (p<0.001).
CONCLUSIONS: The risk of a fulminant course of acute myocarditis was high in patients with elevated C-reactive protein, and creatine kinase concentrations, decreased left ventricular ejection fraction, and intraventricular conduction disturbances at the time of admission.

PMID 15277731  Circ J. 2004 Aug;68(8):734-9.
著者: S C Smith, J H Ladenson, J W Mason, A S Jaffe
雑誌名: Circulation. 1997 Jan 7;95(1):163-8.
Abstract/Text BACKGROUND: Endomyocardial biopsy is currently the standard method used to diagnose myocarditis. However, it is invasive and has a low diagnostic yield. Because the histological diagnosis of myocarditis requires the presence of myocyte injury, we sought to determine whether measurement of cardiac troponin I (cTnI), which is a serum marker with high sensitivity and specificity for cardiac myocyte injury, could aid in the diagnosis of myocarditis.
METHODS AND RESULTS: To validate this approach, cTnI values were first measured in mice with autoimmune myocarditis. cTnI values were elevated in 24 of 26 mice with myocarditis but were not elevated in any of the control animals (P < .001). Next, cTnI values were measured in the sera from 88 patients referred to the Myocarditis Treatment Trial and were compared with creatine kinase-MB (CK-MB) values measured in the same patients. cTnI values were elevated in 18 (34%) of 53 patients with myocarditis and in only 4 (11%) of 35 patients without myocarditis (P = .01). In contrast, CK-MB values were elevated in only 3 (5.7%) of 53 patients with myocarditis and 0 of 35 patients without myocarditis (P = .27). Thus, elevations of cTnI occurred more frequently than did elevations of CK-MB in patients with biopsy-proven myocarditis (P = .001). Importantly, elevations of cTnI in patients with myocarditis were significantly correlated with < or = 1 month duration of heart failure symptoms (P = .02), suggesting that the majority of myocyte necrosis occurs early, and thus the window for diagnosis and treatment may be relatively brief.
CONCLUSIONS: cTnI was superior to CK-MB for detection of myocyte injury in myocarditis, and cTnI elevations were substantially more common in the first month after the onset of heart failure symptoms.

PMID 8994432  Circulation. 1997 Jan 7;95(1):163-8.
著者: Mototsugu Nishii, Takayuki Inomata, Hitoshi Takehana, Ichiro Takeuchi, Hironari Nakano, Toshimi Koitabashi, Jun-ichi Nakahata, Naoyoshi Aoyama, Tohru Izumi
雑誌名: J Am Coll Cardiol. 2004 Sep 15;44(6):1292-7. doi: 10.1016/j.jacc.2004.01.055.
Abstract/Text OBJECTIVES: We assessed the significance of serum cytokine levels in patients with fulminant myocarditis.
BACKGROUND: Although many investigations have demonstrated the crucial role of cytokines in the development of myocarditis, it remains uncertain whether serum levels of cytokines enable one to predict the prognosis of human myocarditis, especially concerning cardiogenic shock (CS) requiring a mechanical cardiopulmonary support system (MCSS).
METHODS: We studied 22 consecutive patients with fulminant myocarditis and compared them with 15 patients with acute myocardial infarction (AMI) requiring MCSS. The patients with myocarditis were classified into three groups: eight patients with CS requiring MCSS on admission (group 1); six patients who unexpectedly lapsed into CS requiring MCSS more than two days after catecholamine had been initiated (group 2); and eight patients without MCSS (group 3). Furthermore, 14 patients with myocarditis requiring MCSS were divided into a fatal group (n = 5) and a survival group (n = 9). Biochemical markers, including serum cytokine levels and hemodynamic variables on admission, were analyzed.
RESULTS: Serum levels of interleukin (IL)-10 and tumor necrosis factor-alpha, but not other cytokines, were significantly higher in myocarditis than in AMI. Only serum levels of IL-10 were significantly higher in group 1 and 2 than in group 3 (49.1 +/- 37.5/20.7 +/- 17.6 pg/ml vs. 2.4 +/- 1.1 pg/ml; p = 0.0008/0.0012). Serum IL-10 levels were also significantly higher in the fatal group than in the survival group with myocarditis (74.0 +/- 27.0 pg/ml vs. 16.4 +/- 8.8 pg/ml; p = 0.003).
CONCLUSIONS: Serum IL-10 levels on admission enabled one to predict subsequent CS requiring MCSS and mortality of fulminant myocarditis patients.

PMID 15364334  J Am Coll Cardiol. 2004 Sep 15;44(6):1292-7. doi: 10.10・・・
著者: W M Franz, A Remppis, R Kandolf, W Kübler, H A Katus
雑誌名: Clin Chem. 1996 Feb;42(2):340-1.
Abstract/Text
PMID 8595741  Clin Chem. 1996 Feb;42(2):340-1.
著者: B Lauer, C Niederau, U Kühl, M Schannwell, M Pauschinger, B E Strauer, H P Schultheiss
雑誌名: J Am Coll Cardiol. 1997 Nov 1;30(5):1354-9.
Abstract/Text OBJECTIVES: The present study investigated whether myocyte injury can be assessed sensitively by measurement of serum levels of cardiac troponin T (cTnT) in patients with clinically suspected myocarditis and whether cTnT levels may predict the results of histologic and immunohistologic analysis of endomyocardial biopsy specimens.
BACKGROUND: Conventionally used laboratory variables often fail to show myocyte injury in patients with clinically suspected myocarditis, possibly because of a low extent of myocardial injury in these patients. Sensitive variables for myocyte injury have not yet been investigated.
METHODS: Eighty patients with clinically suspected myocarditis were screened for creatine kinase (CK) activity, MB isoform of CK (CK-MB) activity and cTnT. Endomyocardial biopsy specimens were examined histologically and immunohistologically.
RESULTS: cTnT was elevated in 28 of 80 patients with clinically suspected myocarditis, CK in 4 and CK-MB in 1. Histologic analysis alone of the endomyocardial biopsy specimen revealed evidence of myocarditis in only five patients, all with elevated cTnT levels. Twenty-three of 28 patients with elevated cTnT levels had histologically negative findings for myocarditis. Additional immunohistologic analysis revealed evidence of myocarditis in 26 (93%) of 28 patients with elevated cTnT levels and in 23 (44%) of 52 patients with normal cTnT levels. Mean cTnT levels were higher in patients with myocarditis proved histologically or immunohistologically, or both, than in patients without myocarditis (0.59 +/- 1.68 vs. 0.04 +/- 0.05, p < 0.001).
CONCLUSIONS: Measurement of serum levels of cTnT provides evidence of myocyte injury in patients with clinically suspected myocarditis more sensitively than does conventional determination of cardiac enzyme levels. Myocardial cell damage may be present even in the absence of histologic signs of myocarditis. Additional immunohistologic analysis often shows lymphocytic infiltrates in these patients. Elevated levels of cTnT are highly predictive for myocarditis in this group.

PMID 9350939  J Am Coll Cardiol. 1997 Nov 1;30(5):1354-9.
著者: J Soongswang, K Durongpisitkul, A Nana, D Laohaprasittiporn, C Kangkagate, K Punlee, N Limpimwong
雑誌名: Pediatr Cardiol. 2005 Jan-Feb;26(1):45-9. doi: 10.1007/s00246-004-0677-6.
Abstract/Text This study was conducted to assess the use of serum cardiac troponin T (cTnT) level as a noninvasive indicator to diagnose acute myocarditis in children. Noninvasive conventional methods often fail to diagnose myocarditis, A median cTnT level of 0.088 ng/ml (0.04-3.11) was reported in pediatric patients with acute myocarditis in our previous study. Hence, we attempted to determine the cutfoff level of cTnT to diagnose acute myocarditis in children. Pediatric patients with clinically suspected myocarditis or dilated cardiomyopathy (DCM) and a control group were recruited. History, physical examination, elctrocardiogram, chest roentgenogram, echocardiogram, cTnT level, and/or endomyocardial biopsy and clinical course were studied. The gold standard to diagnose acute myocarditis was endomyocardial biopsy proved according to the Dallas criteria and/or recovery from cardiovascular problems within 6 months of follow-up. Forty-three patients were admitted due to cardiovascular problems from primary myocardial dysfunction. Twenty-four patients were diagnosed as acute myocarditis (group 1), 19 were idiopathic chronic DCM (group 2), and 21 patients had moderate to large ventricular septal defect and congestive heart failure (group 3). Median cTnT level was statistically higher in (group 1) compared to groups 2 and 3. Ejection fraction (EF) and left ventricular end diastolic dimension (LVEDd) z score of acute myocarditis were 38.5% (range, 21-67) and 1.3 (range, -0.8-3.0), respectively, which were significantly better than DCM [28.0% (range, 17-45) and 6.0 (range, 2.0-10.0)]. The cutoff point of cTnT level to diagnose acute myocarditis was 0.052 ng/ml (sensitivity, 71%; specificity, 86%). cTnT level, EF, and LVEDd z score did not predict short-term outcomes of patients. In acute myocarditis, cTnT level and EF were significantly higher and LVEDd z score was significantly lower than in DCM. However, the three parameters had no significant effect on outcomes of the patients. Our data show that cardiac a cTnT level of 0.052 ng/ml is an appropriate cutoff point for the diagnosis of acute myocarditis.

PMID 15793653  Pediatr Cardiol. 2005 Jan-Feb;26(1):45-9. doi: 10.1007/・・・
著者: M Kodama, H Oda, M Okabe, Y Aizawa, T Izumi
雑誌名: Jpn Circ J. 2001 Nov;65(11):961-4.
Abstract/Text The frequency of myocarditis and the prognosis for patients remains uncertain and, moreover, the clinical classification of myocarditis is controversial. From 1985 to 2000, 71 adult patients with clinically suspected myocarditis were admitted to 11 cardiovascular centers. Of these, 48 cases had histology proven myocarditis: 41 cases of lymphocytic myocarditis, 6 of giant cell myocarditis and 1 of eosinophilic myocarditis. Myocarditis was classified as acute (30 cases) or chronic (18 cases) according to the onset of the disease, and acute myocarditis was further categorized into common or fulminant type depending on whether or not patients required mechanical circulatory support in the management of heart failure (9 and 21 cases, respectively). Chronic myocarditis was divided into 3 subgroups: a persistent type lasting over 3 months after distinct onset (3 cases), a recurrent type (2 cases) and a latent form (13 cases). The early mortality of these 5 subtypes of myocarditis were acute common 22%, acute fluminant 43%, chronic persistent 33%, chronic recurrent 50%, and chronic latent 38%. The overall early mortality of all patients with myocarditis was 38% in spite of aggressive treatment during hospitalization. On the other hand, the long-term prognosis of patients with myocarditis was favorable; only 4 cases, who survived the active phase, died in the late phase: 1 had fulminant myocarditis and the other 3 had the chronic latent form. Thus, the early mortality of patients with myocarditis was very high regardless of the subtype, but if patients can survive the active phase, they have a favorable prognosis except with the chronic latent form.

PMID 11716247  Jpn Circ J. 2001 Nov;65(11):961-4.
著者: R E McCarthy, J P Boehmer, R H Hruban, G M Hutchins, E K Kasper, J M Hare, K L Baughman
雑誌名: N Engl J Med. 2000 Mar 9;342(10):690-5. doi: 10.1056/NEJM200003093421003.
Abstract/Text BACKGROUND: Lymphocytic myocarditis causes left ventricular dysfunction that may be persistent or reversible. There are no clinical criteria that predict which patients will recover ventricular function and which cases will progress to dilated cardiomyopathy. We hypothesized that patients with fulminant myocarditis may have a better long-term prognosis than those with acute (nonfulminant) myocarditis.
METHODS: We identified 147 patients considered to have myocarditis according to the findings on endomyocardial biopsy and the Dallas histopathological criteria. Fulminant myocarditis was diagnosed on the basis of clinical features at presentation, including the presence of severe hemodynamic compromise, rapid onset of symptoms, and fever. Patients with acute myocarditis did not have these features. The incidence of the end point of this study, death or heart transplantation, was ascertained by contact with the patient or the patient's family or by a search of the National Death Index. The average period of follow-up was 5.6 years.
RESULTS: A total of 15 patients met the criteria for fulminant myocarditis, and 132 met the criteria for acute myocarditis. Among the patients with fulminant myocarditis, 93 percent were alive without having received a heart transplant 11 years after biopsy (95 percent confidence interval, 59 to 99 percent), as compared with only 45 percent of those with acute myocarditis (95 percent confidence interval, 30 to 58 percent; P=0.05 by the log-rank test). Fulminant myocarditis was an independent predictor of survival after adjustments were made for age, histopathological findings, and hemodynamic variables. The rate of transplantation-free survival did not differ significantly between the patients considered to have borderline myocarditis and those considered to have active myocarditis according to the Dallas histopathological criteria.
CONCLUSIONS: Fulminant myocarditis is a distinct clinical entity with an excellent long-term prognosis. Aggressive hemodynamic support is warranted for patients with this condition.

PMID 10706898  N Engl J Med. 2000 Mar 9;342(10):690-5. doi: 10.1056/NE・・・
著者: Yasuhide Asaumi, Satoshi Yasuda, Isao Morii, Hiroyuki Kakuchi, Yoritaka Otsuka, Atsushi Kawamura, Yoshikado Sasako, Takeshi Nakatani, Hiroshi Nonogi, Shunichi Miyazaki
雑誌名: Eur Heart J. 2005 Oct;26(20):2185-92. doi: 10.1093/eurheartj/ehi411. Epub 2005 Jul 13.
Abstract/Text AIMS: The clinical outcome of severe acute myocarditis patients with cardiogenic shock who require circulatory support devices is not well known. We studied the survival and clinical courses of patients with fulminant myocarditis supported by percutaneous extracorporeal membrane oxygenation (ECMO) and compared them with those of patients with acute non-fulminant myocarditis.
METHODS AND RESULTS: Patients with acute myocarditis were divided into the following two groups. Fourteen patients who required ECMO for cardiogenic shock were defined as having fulminant myocarditis (F group), whereas 13 patients who had an acute onset of symptoms, but did not have compromised, were defined as having acute non-fulminant myocarditis (NF group). In the F group, 10 patients were weaned successfully from percutaneous ECMO. Therefore, the overall acute survival rate was 71%. Patients who were not weaned from ECMO showed smaller left ventricular end-diastolic and end-systolic dimensions, thicker left ventricular wall, and higher creatine phosphokinase MB isoform levels than those who were weaned from ECMO. When compared with patients in the NF group, the fractional shortening in the F group was more severely decreased in the acute phase [F: 10+/-4 vs. NF: 23+/-8% (mean+/-SD), P<0.001], but recovered in the chronic phase (F: 33+/-7 vs. NF: 34+/-6%). The prevalence of adverse clinical events in both groups was similar during the follow-up period of 50 months.
CONCLUSION: In patients with fulminant myocarditis, percutaneous ECMO is a highly effective form of a haemodynamic support. Once a patient recovers from inflammatory myocardial damage, the subsequent clinical outcome is favourable, similar to that observed in patients with acute non-fulminant myocarditis.

PMID 16014643  Eur Heart J. 2005 Oct;26(20):2185-92. doi: 10.1093/eurh・・・
著者:
雑誌名: N Engl J Med. 1987 Jun 4;316(23):1429-35. doi: 10.1056/NEJM198706043162301.
Abstract/Text To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure.

PMID 2883575  N Engl J Med. 1987 Jun 4;316(23):1429-35. doi: 10.1056/・・・
著者: B Pitt, F Zannad, W J Remme, R Cody, A Castaigne, A Perez, J Palensky, J Wittes
雑誌名: N Engl J Med. 1999 Sep 2;341(10):709-17. doi: 10.1056/NEJM199909023411001.
Abstract/Text BACKGROUND AND METHODS: Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes.
RESULTS: The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients.
CONCLUSIONS: Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.

PMID 10471456  N Engl J Med. 1999 Sep 2;341(10):709-17. doi: 10.1056/N・・・
著者: Bertram Pitt, Willem Remme, Faiez Zannad, James Neaton, Felipe Martinez, Barbara Roniker, Richard Bittman, Steve Hurley, Jay Kleiman, Marjorie Gatlin, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators
雑誌名: N Engl J Med. 2003 Apr 3;348(14):1309-21. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.
Abstract/Text BACKGROUND: Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.
METHODS: Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3319 patients) or placebo (3313 patients) [correction] in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia.
RESULTS: During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P=0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P=0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001).
CONCLUSIONS: The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

Copyright 2003 Massachusetts Medical Society
PMID 12668699  N Engl J Med. 2003 Apr 3;348(14):1309-21. doi: 10.1056/・・・
著者: Kenneth Dickstein, Alain Cohen-Solal, Gerasimos Filippatos, John J V McMurray, Piotr Ponikowski, Philip Alexander Poole-Wilson, Anna Strömberg, Dirk J van Veldhuisen, Dan Atar, Arno W Hoes, Andre Keren, Alexandre Mebazaa, Markku Nieminen, Silvia Giuliana Priori, Karl Swedberg, ESC Committee for Practice Guidelines (CPG)
雑誌名: Eur Heart J. 2008 Oct;29(19):2388-442. doi: 10.1093/eurheartj/ehn309. Epub 2008 Sep 17.
Abstract/Text
PMID 18799522  Eur Heart J. 2008 Oct;29(19):2388-442. doi: 10.1093/eur・・・
著者: Jie Xiao, Miho Shimada, Wenling Liu, Dayi Hu, Akira Matsumori
雑誌名: Eur J Heart Fail. 2009 Apr;11(4):349-53. doi: 10.1093/eurjhf/hfp023. Epub 2009 Feb 12.
Abstract/Text AIMS: Inflammation contributes to increased cardiovascular morbidity and mortality associated with activation of the renin-angiotensin-aldosterone system. The aim of this study was to investigate whether eplerenone, a selective aldosterone receptor antagonist, has anti-inflammatory effects on viral myocarditis.
METHODS AND RESULTS: Four-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the encephalomyocarditis (EMC) virus. Mice were fed with standard chow (control) or with chow containing 2.5 mg/kg of eplerenone, starting either on day 0 (inoculation) or day 7. Survival at 28 days was significantly higher in the mice which started eplerenone treatment on day 0 (35 vs. 15% in controls, each n = 40, P < 0.05). The area of myocardial fibrosis on day 28 was significantly smaller in the eplerenone-treated mice than in controls (19.8 +/- 2.6%, n = 14, vs. 33.4 +/- 5.4%, n = 6, mean +/- SEM, P < 0.05). Gene expression of mouse mast cell proteases-4 and -5, matrix metalloproteinase-9, and type I procollagen on day 6 after EMC virus inoculation was significantly decreased in the hearts of eplerenone-treated mice.
CONCLUSION: These results suggest that eplerenone has anti-inflammatory effects, and exerts its beneficial effects on viral myocarditis by suppression of genes related to mast cells and cardiac remodelling in the hearts of mice.

PMID 19213804  Eur J Heart Fail. 2009 Apr;11(4):349-53. doi: 10.1093/e・・・
著者: Faiez Zannad, John J V McMurray, Henry Krum, Dirk J van Veldhuisen, Karl Swedberg, Harry Shi, John Vincent, Stuart J Pocock, Bertram Pitt, EMPHASIS-HF Study Group
雑誌名: N Engl J Med. 2011 Jan 6;364(1):11-21. doi: 10.1056/NEJMoa1009492. Epub 2010 Nov 14.
Abstract/Text BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms.
METHODS: In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.
RESULTS: The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001).
CONCLUSIONS: Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).

PMID 21073363  N Engl J Med. 2011 Jan 6;364(1):11-21. doi: 10.1056/NEJ・・・
著者: Ingrid Kindermann, Michael Kindermann, Reinhard Kandolf, Karin Klingel, Burkhard Bültmann, Thomas Müller, Angelika Lindinger, Michael Böhm
雑誌名: Circulation. 2008 Aug 5;118(6):639-48. doi: 10.1161/CIRCULATIONAHA.108.769489. Epub 2008 Jul 21.
Abstract/Text BACKGROUND: The objective of this study was to identify the prognostic indicators in patients with suspected myocarditis who underwent endomyocardial biopsy.
METHODS AND RESULTS: Between 1994 and 2007, 181 consecutive patients (age, 42+/-15 years) with clinically suspected viral myocarditis were enrolled and followed up for a mean of 59+/-42 months. Endomyocardial biopsies were studied for inflammation with histological (Dallas) and immunohistological criteria. Virus genome was detected by polymerase chain reaction. The primary end point was time to cardiac death or heart transplantation. In 38% of the patients (n=69), the Dallas criteria were positive. Immunohistological signs of inflammation were shown in 50% (n=91). Genomes of cardiotropic virus species were detected in 79 patients (44%). During follow-up, 22% of the patients (n=40) reached the primary end point. Three independent predictors were identified for the primary end point, namely New York Heart Association class III or IV at entry (hazard ratio, 3.20; 95% confidence interval, 1.36 to 7.57; P=0.008), immunohistological evidence of inflammatory infiltrates in the myocardium (hazard ratio, 3.46; 95% confidence interval, 1.39 to 8.62; P=0.008), and beta-blocker therapy (hazard ratio, 0.43; 95% confidence interval, 0.21 to 0.91; P=0.027). Ejection fraction, left ventricular end-diastolic pressure, and left ventricular end-diastolic dimension index were predictive only in univariate, not in multivariate, analysis. Neither the Dallas criteria nor the detection of viral genome was a predictor of outcome.
CONCLUSIONS: For patients with suspected myocarditis, advanced New York Heart Association functional class, immunohistological signs of inflammation, and lack of beta-blocker therapy, but not histology (positive Dallas criteria) or viral genome detection, are related to poor outcome.

PMID 18645053  Circulation. 2008 Aug 5;118(6):639-48. doi: 10.1161/CIR・・・
著者: Barry J Maron
雑誌名: N Engl J Med. 2003 Sep 11;349(11):1064-75. doi: 10.1056/NEJMra022783.
Abstract/Text
PMID 12968091  N Engl J Med. 2003 Sep 11;349(11):1064-75. doi: 10.1056・・・
著者: A E Cabinian, R J Kiel, F Smith, K L Ho, R Khatib, M P Reyes
雑誌名: J Lab Clin Med. 1990 Apr;115(4):454-62.
Abstract/Text The effects of T lymphocyte suppression on coxsackievirus B3 (CB3) myocarditis and its augmentation by exercise were determined in this study. Three-week-old male C3H/HeN mice were divided into four groups. Group 1 mice were infected intraperitoneally (IP) on day 0 with CB3 10(2.5) TCID50, were made to swim daily from days 1 to 9, and were immunosuppressed with daily doses of cyclosporine A (25 mg/kg IP) from days -2 to 8, plus 0.1 ml antithymocyte 1.2 IgG 2a monoclonal antibody IP on day 0. Mice in group 2 were infected and made to swim daily from days 1 to 9. Mice in group 3 were infected and immunosuppressed as outlined. Mice in group 4 were infected IP with CB3. Mortality rates during the acute phase of infection (days 1 to 9) were as follows: group 1, 4% (1/25); group 2, 52% (13/25); groups 3 and 4, 0. Overall mortality rates through day 21 were as follows: group 1, 67% (17/25); group 2, 72% (18/25); group 3, 40% (10/25); and group 4, 4% (1/25). Mean viral titers in serum were highest in the immunosuppressed groups throughout the study. Myocardial viral titers (mean log10 TCID50) were higher in group 2 mice than in group 1 on days 6 (10(6.9) vs 10(4.6)) and 9 (10(8.4) vs 10(7)); however, these titers peaked in group 1 mice on day 13 (10(9.7)). Myocardial inflammation, necrosis, and mean heart weight/body weight ratios were lower in group 1 compared with group 2 on days 6 and 9 but were maximal on day 13 in group 1. Neutralizing antibody titers were lower in immunosuppressed mice on days 6 and 9; however, a rebound increase occurred on day 13.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 2157783  J Lab Clin Med. 1990 Apr;115(4):454-62.
著者: Saeko Yoshizawa, Tomoko Sugiyama Kato, Donna Mancini, Charles C Marboe
雑誌名: Int Heart J. 2013;54(3):146-8. doi: 10.1536/ihj.54.146.
Abstract/Text Eosinophilic infiltration of the myocardium is occasionally observed as an incidental histological finding in endomyocardial biopsy specimens before heart transplantation (HTx) as well as in explanted heart obtained at the time of HTx. However, the indications for HTx in these patients have not yet been fully established. We investigated the pre-HTx characteristics of the recipients with myocardial eosinophilic infiltration in the explanted heart and diagnosed as hypersensitivity myocarditis (HSM) (21 among 761 recipients, 2.8%). Dobutamine, a common cause of HSM, was administered to 12 patients (57%). Ten patients (47.6%) were on milrinone and 4 (19.0%) were on ventricular assist devices. Post-transplant survival of HSM patients was comparable to that of patients transplanted for active myocarditis or other cause of heart failure. In conclusion, myocardial eosinophilic infiltration is associated with multiple medications in patients with advanced heart failure; however, it does not affect the post-transplant prognosis.

PMID 23774237  Int Heart J. 2013;54(3):146-8. doi: 10.1536/ihj.54.146.・・・
著者: Michela Brambatti, Maria Vittoria Matassini, Eric D Adler, Karin Klingel, Paolo G Camici, Enrico Ammirati
雑誌名: J Am Coll Cardiol. 2017 Nov 7;70(19):2363-2375. doi: 10.1016/j.jacc.2017.09.023.
Abstract/Text BACKGROUND: Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.
OBJECTIVES: Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.
METHODS: The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.
RESULTS: Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).
CONCLUSIONS: EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 29096807  J Am Coll Cardiol. 2017 Nov 7;70(19):2363-2375. doi: 10・・・
著者: Takafumi Koyama, Hiroyuki Yamamoto, Manabu Matsumoto, Jun Isogai, Tadashi Isomura, Shinji Tanaka
雑誌名: Front Cardiovasc Med. 2020;7:589212. doi: 10.3389/fcvm.2020.589212. Epub 2020 Oct 29.
Abstract/Text Löffler's endocarditis (cardiac involvement in hypereosinophilic syndrome) is rare yet life-threatening if left untreated. We describe a case of hypereosinophilic syndrome presenting as a cardiac mass with an abnormal electrocardiogram. Diagnostic studies of the cardiac mass strongly suggested a malignant cardiac tumor invading the papillary muscle. Thus, excision of the cardiac mass and endomyocardial resection with mitral valve replacement were successfully performed. Pathology revealed various stages of thrombosis and irreversible myocardial damage caused by eosinophilic infiltration with no malignancy, leading to the correct diagnosis of late-stage Löffler's endocarditis. The subsequent combination of anticoagulation and corticosteroids was effective with a favorable outcome. This case highlights pitfalls in multimodality imaging of cardiac thrombus and the clinical significance of considering Löffler's endocarditis in the diagnostic work-up of a cardiac mass.

Copyright © 2020 Koyama, Yamamoto, Matsumoto, Isogai, Isomura and Tanaka.
PMID 33195478  Front Cardiovasc Med. 2020;7:589212. doi: 10.3389/fcvm.・・・
著者: Nicola L Diny, Noel R Rose, Daniela Čiháková
雑誌名: Front Immunol. 2017;8:484. doi: 10.3389/fimmu.2017.00484. Epub 2017 Apr 27.
Abstract/Text Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

PMID 28496445  Front Immunol. 2017;8:484. doi: 10.3389/fimmu.2017.0048・・・
著者: Nicola L Diny, G Christian Baldeviano, Monica V Talor, Jobert G Barin, SuFey Ong, Djahida Bedja, Allison G Hays, Nisha A Gilotra, Isabelle Coppens, Noel R Rose, Daniela Čiháková
雑誌名: J Exp Med. 2017 Apr 3;214(4):943-957. doi: 10.1084/jem.20161702. Epub 2017 Mar 16.
Abstract/Text Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. Eosinophil-deficient ΔdblGATA1 mice, in contrast to WT mice, showed no signs of heart failure by echocardiography. Induction of EAM in hypereosinophilic IL-5Tg mice resulted in eosinophilic myocarditis with severe ventricular and atrial inflammation, which progressed to severe DCMi. This was not a direct effect of IL-5, as IL-5TgΔdblGATA1 mice were protected from DCMi, whereas IL-5-/- mice exhibited DCMi comparable with WT mice. Eosinophils drove progression to DCMi through their production of IL-4. Our experiments showed eosinophils were the major IL-4-expressing cell type in the heart during EAM, IL-4-/- mice were protected from DCMi like ΔdblGATA1 mice, and eosinophil-specific IL-4 deletion resulted in improved heart function. In conclusion, eosinophils drive progression of myocarditis to DCMi, cause severe DCMi when present in large numbers, and mediate this process through IL-4.

© 2017 Diny et al.
PMID 28302646  J Exp Med. 2017 Apr 3;214(4):943-957. doi: 10.1084/jem.・・・
著者: Hiroto Aota, Hiroyuki Yamamoto, Jun Isogai, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Takahiro Tanaka
雑誌名: Front Cardiovasc Med. 2021;8:678973. doi: 10.3389/fcvm.2021.678973. Epub 2021 Jun 23.
Abstract/Text Eosinophilic myocarditis is a rare subtype of myocarditis characterized by myocardial eosinophilic infiltration, and it is potentially fatal if left untreated. Although endomyocardial biopsy (EMB) is a cornerstone for the histological diagnosis of acute eosinophilic myocarditis (AEM), as it is an invasive procedure and has a low diagnostic accuracy, the diagnosis of AEM with hemodynamic instability remains challenging. We describe a case of AEM presenting as low-flow heart failure with preserved ejection fraction (HFpEF), with rapid progression to cardiogenic shock. The constellation of peripheral eosinophilia, increased left ventricular wall thickness, and HFpEF raised the suspicion of AEM. Contrast-enhanced computed tomography (CT) scan revealed heterogeneous hypoenhancement localized in the basal-to-mid septal and mid anterolateral walls of the left ventricle, strongly suggestive of acute inflammation. Based upon these findings, we performed CT-guided EMB, which lead to a definitive diagnosis. Subsequent high-dose corticosteroids allowed a rapid and dramatic recovery and normalization of cardiac structure and function. This case highlights the clinical importance of assessing AEM as a rare cause of HFpEF and the usefulness of CT-guided EMB in patients with hemodynamic instability.

Copyright © 2021 Aota, Yamamoto, Isogai, Imanaka-Yoshida, Hiroe and Tanaka.
PMID 34250040  Front Cardiovasc Med. 2021;8:678973. doi: 10.3389/fcvm.・・・
著者: Giovanni Donato Aquaro, Matteo Perfetti, Giovanni Camastra, Lorenzo Monti, Santo Dellegrottaglie, Claudio Moro, Alessia Pepe, Giancarlo Todiere, Chiara Lanzillo, Alessandra Scatteia, Mauro Di Roma, Gianluca Pontone, Martina Perazzolo Marra, Andrea Barison, Gianluca Di Bella, Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology
雑誌名: J Am Coll Cardiol. 2017 Oct 17;70(16):1977-1987. doi: 10.1016/j.jacc.2017.08.044.
Abstract/Text BACKGROUND: The prognostic role of cardiac magnetic resonance (CMR) and late gadolinium enhancement (LGE) has not been clarified in acute myocarditis (AM) with preserved left ventricular (LV) ejection fraction (EF).
OBJECTIVES: This study sought to evaluate the role of CMR and LGE in the prognosis of AM with preserved LVEF.
METHODS: This study analyzed data from ITAMY (ITalian multicenter study on Acute MYocarditis) and evaluated CMR results from 386 patients (299 male; mean age 35 ± 15 years) with AM and preserved LVEF. Clinical follow-up was performed for a median of 1,572 days. A clinical combined endpoint of cardiac death, appropriate implantable cardioverter-defibrillator firing, resuscitated cardiac arrest, and hospitalization for heart failure was used.
RESULTS: Among the 374 patients with suitable images, LGE involved the subepicardial layer inferior and lateral wall in 154 patients (41%; IL group), the midwall layer of the anteroseptal wall in 135 patients (36%; AS [anteroseptal] group), and other segments in 59 patients (16%; other-LGE group), and it was absent in 26 patients (no-LGE group). The AS group had a greater extent of LGE and a higher LV end-diastolic volume index than other groups, but levels of inflammatory markers were lower than in the other groups. Kaplan-Meier curve analysis indicated that the AS group had a worse prognosis than the other groups (p < 0.0001). Finally, in multivariable analysis, AS LGE was the best independent CMR predictor of the combined endpoint (odds ratio: 2.73; 95% confidence interval: 1.2 to 5.9; p = 0.01).
CONCLUSIONS: In patients with AM and preserved LVEF, LGE in the midwall layer of the AS myocardial segment is associated with a worse prognosis than other patterns of presentation.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 29025554  J Am Coll Cardiol. 2017 Oct 17;70(16):1977-1987. doi: 1・・・
著者: Hiroyuki Yamamoto, Toru Hashimoto, Keiko Ohta-Ogo, Hatuse Ishibashi-Ueda, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Tomoki Yokochi
雑誌名: Cardiovasc Pathol. 2018 Nov - Dec;37:54-57. doi: 10.1016/j.carpath.2018.10.003. Epub 2018 Oct 9.
Abstract/Text Vaccine-associated myocarditis is an extremely rare, yet potentially lethal disease, which requires early diagnosis and prompt treatment. However, its pathogenesis remains elusive. We report the first case of biopsy-proven eosinophilic myocarditis related to tetanus toxoid immunization, with unique histopathologic findings, characterized by perivascular eosinophilic infiltrates with myocyte necrosis and abundant interstitial lymphocytic infiltrates with myocyte necrosis, separately. A systemic high-dose corticosteroid treatment had a dramatic beneficial effect on hemodynamic instability and resulted in complete recovery. This case highlights the value of endomyocardial biopsy in establishing a definite diagnosis and understanding the pathogenesis of vaccine-associated myocarditis.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PMID 30343188  Cardiovasc Pathol. 2018 Nov - Dec;37:54-57. doi: 10.101・・・
著者: Hidetomo Maruyoshi, Satoshi Nakatani, Yoshio Yasumura, Akihisa Hanatani, Tomoyoshi Yamaguchi, Chikao Yutani, Hatsue Ishibashi-Ueda, Kunio Miyatake, Masakazu Yamagishi
雑誌名: Heart Vessels. 2003 Mar;18(1):43-6. doi: 10.1007/s003800300007.
Abstract/Text A73-year-old man with a history of bronchial asthma and atrial fibrillation was admitted to our hospital because of dyspnea and back pain. Blood analysis revealed a marked increase in total blood cell and eosinophil counts. The creatine kinase and creatine kinase-MB increased slightly. The ECG demonstrated significant ST-segment depression that mimicked acute posterior myocardial infarction. Emergent coronary angiography showed no stenotic lesions. The histological findings in endomyocardial biopsy showed thickened endocardium associated with significant eosinophilic infiltration, which was compatible with Löffler's endocarditis. After the administration of prednisolone, the patient's general condition, eosinophilia, ECG abnormalities, and histological findings were improved dramatically. The endomyocardial biopsy in the acute phase was helpful for diagnosis and therapeutic decision-making.

PMID 12644881  Heart Vessels. 2003 Mar;18(1):43-6. doi: 10.1007/s00380・・・
著者: S Hayashi, M Isobe, Y Okubo, J Suzuki, Y Yazaki, M Sekiguchi
雑誌名: Heart Vessels. 1999;14(2):104-8.
Abstract/Text A 62-year-old man with acute eosinophilic endomyocarditis developed congestive heart failure. The biopsy specimens revealed degranulated eosinophils and eosinophil cationic protein (ECP) in the endocardium, and in activated eosinophils and the myocardial interstitium. On electronmicroscopy, a characteristic cardiac myocytolytic change showing disruption at the intercellular junctional site was observed. After steroid treatment, clinical symptoms, systolic dysfunction and laboratory data dramatically improved. In the subsequent biopsy specimens, eosinophilic infiltration and ECP disappeared. Steroid therapy provided a beneficial effect in preventing the progression of cardiac damage. This effect was clearly documented by histochemical studies of the serial endomyocardial biopsy samples.

PMID 10651187  Heart Vessels. 1999;14(2):104-8.
著者: Mizuhiro Arima, Tatsuji Kanoh, Yasunobu Kawano, Tetsuya Oigawa, Shinichiro Yamagami, Shigeru Matsuda
雑誌名: Int J Cardiol. 2002 Jul;84(1):97-9.
Abstract/Text
PMID 12104073  Int J Cardiol. 2002 Jul;84(1):97-9.
著者: C H Kim, R E Vlietstra, W D Edwards, G S Reeder, G J Gleich
雑誌名: Am J Cardiol. 1984 May 15;53(10):1472-3.
Abstract/Text
PMID 6720598  Am J Cardiol. 1984 May 15;53(10):1472-3.
著者: Y Uetsuka, S Kasahara, N Tanaka, M Sekiguchi, M Hiroe, Z X Yu, S Hosoda
雑誌名: Heart Vessels Suppl. 1990;5:8-12.
Abstract/Text A 70-year-old woman with active hypereosinophilic myocarditis presented with high fever and heart failure. Repeated right ventricular endomyocardial biopsies and 201-T1 myocardial scans before and after steroid therapy suggested that this treatment reversed the cardiac injury. Patients with hypereosinophilia may die from complications of eosinophilic infiltration and fibrosis in target organs, especially the heart. The findings in this patient suggest that steroids have benefit in this disease, at least in the short term.

PMID 2093721  Heart Vessels Suppl. 1990;5:8-12.
著者: J W Mason, J B O'Connell, A Herskowitz, N R Rose, B M McManus, M E Billingham, T E Moon
雑誌名: N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NEJM199508033330501.
Abstract/Text BACKGROUND: Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis and to examine measures of the immune response as predictors of the severity and outcome of disease.
METHODS: We randomly assigned 111 patients with a histopathological diagnosis of myocarditis and a left ventricular ejection fraction of less than 0.45 to receive conventional therapy alone or combined with a 24-week regimen of immunosuppressive therapy. Immunosuppressive therapy consisted of prednisone with either cyclosporine or azathioprine. The primary outcome measure was a change in the left ventricular ejection fraction at 28 weeks.
RESULTS: In the group as a whole, the mean (+/- SE) left ventricular ejection fraction improved from 0.25 +/- 0.01 at base line to 0.34 +/- 0.02 at 28 weeks (P < 0.001). The mean change in the left ventricular ejection fraction at 28 weeks did not differ significantly between the group of patients who received immunosuppressive therapy (a gain of 0.10; 95 percent confidence interval, 0.07 to 0.12) and the control group (a gain of 0.07; 95 percent confidence interval, 0.03 to 0.12). A higher left ventricular ejection fraction at base line, less intensive conventional drug therapy at base line, and a shorter duration of disease, but not the treatment assignment, were positive independent predictors of the left ventricular ejection fraction at week 28. There was no significant difference in survival between the two groups (P = 0.96). The mortality rate for the entire group was 20 percent at 1 year and 56 percent at 4.3 years. Features suggesting an effective inflammatory response were associated with less severe initial disease.
CONCLUSIONS: Our results do not support routine treatment of myocarditis with immunosuppressive drugs. Ventricular function improved regardless of whether patients received immunosuppressive therapy, but long-term mortality was high. Patients with a vigorous inflammatory response had less severe disease.

PMID 7596370  N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NE・・・
著者: Andrea Frustaci, Cristina Chimenti, Fiorella Calabrese, Maurizio Pieroni, Gaetano Thiene, Attilio Maseri
雑誌名: Circulation. 2003 Feb 18;107(6):857-63.
Abstract/Text BACKGROUND: The beneficial effect of immunosuppressive treatment on myocarditis is still controversial, possibly because the immunologic and virological profile of potential candidates is largely unknown.
METHODS AND RESULTS: Out of 652 biopsied patients, 112 had a histological diagnosis of active lymphocytic myocarditis; 41 of these 112 patients were characterized by progressive heart failure despite conventional therapy and were treated with prednisone and azathioprine for 6 months. All were resubmitted to cardiac catheterization, angiography, and endomyocardial biopsy at 1 and 6 months and followed-up for 1 year. A total of 21 patients responded with prompt improvement in left ventricular ejection fraction from 25.7+/-4.1% to 47.1+/-4.4% and showed evidence of healed myocarditis at control biopsy. Conversely, 20 patients failed to respond and showed a histological evolution toward dilated cardiomyopathy: 12 remained stationary, 3 underwent cardiac transplantation, and 5 died. We retrospectively performed a polymerase chain reaction on frozen endomyocardial tissue for the most common cardiotropic viruses and assessed circulating serum cardiac autoantibodies. Viral genomes were present in biopsy specimens of 17 nonresponders (85%), including enterovirus (n=5), Epstein-Barr virus (n=5) adenovirus (n=4), both adenovirus and enterovirus (n=1), influenza A virus (n=1), parvovirus-B19 (n=1), and in 3 responders, who were all positive for hepatitis C virus. Cardiac autoantibodies were present in 19 responders (90%) and in none of the nonresponders.
CONCLUSIONS: In patients with active lymphocytic myocarditis, those with circulating cardiac autoantibodies and no viral genome in the myocardium are the most likely to benefit from immunosuppression. The beneficial effect of immunosuppression in hepatitis C virus myocarditis suggests a relevant immunomediated component of damage.

PMID 12591756  Circulation. 2003 Feb 18;107(6):857-63.
著者: Kenki Enko, Takeshi Tada, Keiko O Ohgo, Satoshi Nagase, Kazufumi Nakamura, Kei Ohta, Shingo Ichiba, Yoshihito Ujike, Yukifumi Nawa, Haruhiko Maruyama, Tohru Ohe, Kengo F Kusano
雑誌名: Circ J. 2009 Jul;73(7):1344-8. Epub 2008 Dec 27.
Abstract/Text A 19-year-old man was transferred to hospital because of myocarditis with cardiogenic shock. Echocardiography showed a left ventricular ejection fraction of 23.8% and an intermediate amount of pericardial effusion. The patient immediately received an intra-aortic balloon pump and percutaneous cardiopulmonary support. Right ventricular endomyocardial biopsy was performed in the acute phase and showed extensive eosinophilic inflammatory cell infiltration, severe interstitial edema and moderate myocardial necrosis. High-dose corticosteroids were administered. Because the patient's antibody titer against Toxocara canis was high and his symptoms had appeared after eating raw deer meat, the diagnosis was fulminant eosinophilic myocarditis caused by a hypersensitivity reaction to visceral larval migrans. After starting high-dose corticosteroids, the ejection fraction dramatically improved, the eosinophilia decreased and the patient made a full recovery.

PMID 19122304  Circ J. 2009 Jul;73(7):1344-8. Epub 2008 Dec 27.

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