日本循環器学会：2023年改訂版 心筋炎の診断・治療に関するガイドライン. 2023. Available from https://www.j-circ.or.jp/cms/wp-content/uploads/2023/03/JCS2023_nagai.pdf.
Ismail Erden, Emine Cakcak Erden, Hakan Ozhan, Cengiz Basar
Acute myocarditis mimicking acute myocardial infarction associated with pandemic 2009 (H1N1) influenza A virus.
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.
Hiroyuki Yamamoto, Katsuya Hashimoto, Yoshihiko Ikeda, Jun Isogai, Toru Hashimoto
The Diagnostic Challenge of Eosinophilic Granulomatosis With Polyangiitis Presenting as Acute Eosinophilic Myocarditis: Case Report and Literature Review.
Front Cardiovasc Med. 2022;9:913724. doi: 10.3389/fcvm.2022.913724. Epub 2022 Jul 7.
Abstract/Text
Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis involving small-to-medium-sized vessels characterized by asthma, vasculitis, and peripheral eosinophilia. EGPA-associated eosinophilic myocarditis (EM) occurs rarely, yet can be fatal if left untreated. Moreover, the accurate diagnosis of EGPA-associated EM without vasculitis is exceptionally difficult because of the overlapping features with EM of other causes. We report a case of probable EGPA with subclinical neurological involvement that presented with acute EM. The constellation of peripheral eosinophilia, left ventricular dysfunction, and normal epicardial coronary arteries raised suspicion of acute EM, which was confirmed by cardiac magnetic resonance (CMR) investigation and endomyocardial biopsy (EMB). Prompt systemic administration of corticosteroids completely restored and normalized myocardial structure and function. Although the patient's history suggested the presumed hypersensitivity myocarditis, EMB revealed EM without vasculitis, not hypersensitivity, leading to a tentative diagnosis of idiopathic hypereosinophilic syndrome. Interestingly, the characteristic findings of vasculitis on CMR imaging strongly suggested EGPA-associated EM. Although the patient had no clinical neurological manifestations, a nerve conduction study confirmed mononeuritis multiplex, leading to the final diagnosis of probable EGPA. Therefore, this case highlights the diagnostic challenge associated with EGPA and the diagnostic synergy of CMR and EMB for an exploratory diagnosis of EGPA-associated EM.
Copyright © 2022 Yamamoto, Hashimoto, Ikeda, Isogai and Hashimoto.
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.
B Lauer, C Niederau, U Kühl, M Schannwell, M Pauschinger, B E Strauer, H P Schultheiss
Cardiac troponin T in patients with clinically suspected myocarditis.
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.
Yih-Sharng Chen, Hsi-Yu Yu, Shu-Chien Huang, Kaung-Ming Chiu, Tzu-Yu Lin, Lin-Ping Lai, Fang-Yue Lin, Shoei-Shan Wang, Shu-Hsun Chu, Wen-Je Ko
Experience and result of extracorporeal membrane oxygenation in treating fulminant myocarditis with shock: what mechanical support should be considered first?
J Heart Lung Transplant. 2005 Jan;24(1):81-7. doi: 10.1016/j.healun.2003.09.038.
Abstract/Text
BACKGROUND: Extracorporeal membrane oxygenation (ECMO), instead of ventricular assist device (VAD), could work as the first-line treatment of choice for fulminant myocarditis (FM) with profound shock if intraaortic balloon pumping was inadequate. We reviewed our experience in treating FM with ECMO and compared it with the literature that described the use of VAD.
METHODS: Fifteen consecutive patients (age 27.1 +/- 19.3 years) who had FM with profound shock were rescued with ECMO emergently. Hypotension, depressed left ventricular ejection fraction (19.1% +/- 6.1%), and oliguria occurred in all patients with high-dose catecholamine (inotropic equivalents: 69.0 +/- 37.7 microg/kg/min) and ventilator support. Before ECMO support, 6 patients received intraaortic balloon pumping support, 5 received external cardiac massage, 5 needed a temporary pacemaker, and 4 needed continuous hemofiltration. The pre-ECMO cardiac enzyme and liver enzyme levels were abnormally high.
RESULTS: Fourteen patients (93.3%) could be weaned off mechanical support. Three of 14 successfully weaned patients died later as a result of complications. Survival to discharge was 73.3%, and none of survivors needed heart transplantation. The ECMO duration was 137.7 +/- 74.5 hours. The ECMO-related neurological complication (6.7%) and the reexploration rate for hemostasis (8.9%) were lower than the myocarditis group supported by VAD from the literature review. The 11 survivors exhibited no cardiac dysfunction during the follow-up period.
CONCLUSIONS: Owning to advantages of fewer complications, easier application, and biventricular support, ECMO can be considered as the first-line treatment of mechanical support for FM with profound shock when intraaortic balloon pumping is inadequate or infeasible.
Alida L P Caforio, Sabine Pankuweit, Eloisa Arbustini, Cristina Basso, Juan Gimeno-Blanes, Stephan B Felix, Michael Fu, Tiina Heliö, Stephane Heymans, Roland Jahns, Karin Klingel, Ales Linhart, Bernhard Maisch, William McKenna, Jens Mogensen, Yigal M Pinto, Arsen Ristic, Heinz-Peter Schultheiss, Hubert Seggewiss, Luigi Tavazzi, Gaetano Thiene, Ali Yilmaz, Philippe Charron, Perry M Elliott, European Society of Cardiology Working Group on Myocardial and Pericardial Diseases
Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.
Eur Heart J. 2013 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.
Abstract/Text
In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
Felix Mahfoud, Barbara Gärtner, Michael Kindermann, Christian Ukena, Katharina Gadomski, Karin Klingel, Reinhard Kandolf, Michael Böhm, Ingrid Kindermann
Virus serology in patients with suspected myocarditis: utility or futility?
Eur Heart J. 2011 Apr;32(7):897-903. doi: 10.1093/eurheartj/ehq493. Epub 2011 Jan 8.
Abstract/Text
AIMS: Serological analyses of viral infection in suspected myocarditis are still widely used, although convincing evidence for their value is lacking. We determined prospectively the diagnostic value of virus serology in comparison with endomyocardial biopsy (EMB) including viral genome detection and immunohistochemistry in patients with clinically suspected myocarditis.
METHODS AND RESULTS: Virus serology and state-of-the-art evaluation of EMB were performed in 124 patients (age 40 ± 15 years) with suspected myocarditis. Endomyocardial biopsy was studied for inflammation with histological and immunohistological criteria. The viral genome was detected in the myocardium by polymerase chain reaction. Acute viral infection with enterovirus, adenovirus, parvovirus B19, cytomegalovirus, human herpesvirus, and Epstein-Barr virus was diagnosed by IgM or IgA in the initial sample or IgG seroconversion in the follow-up sample. Immunohistological signs of inflammation were present in 54 patients. The viral genome was detected in the myocardium of 58 patients (47%). In 20 patients (16%), acute viral infection was diagnosed by serology. Only in 5 out of 124 patients (4%), there was serological evidence of an infection with the same virus that was detected by EMB. Sensitivity and specificity of virus serology were 9 and 77%, respectively. The positive predictive value was 25% and the negative predictive value was 49%. The lack of correlation between serology and EMB remained also for patients with biopsy-proven myocarditis and patients with time from initial symptoms to EMB procedure of ≤1 month.
CONCLUSIONS: For patients with suspected myocarditis, virus serology has no relevance for the diagnosis of myocardial infection. Endomyocardial biopsy remains the gold standard in the diagnostic of viral myocarditis.
G M Zawadowski, K W Klarich, K G Moder, W D Edwards, L T Cooper
A contemporary case series of lupus myocarditis.
Lupus. 2012 Nov;21(13):1378-84. doi: 10.1177/0961203312456752. Epub 2012 Aug 14.
Abstract/Text
OBJECTIVES: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE).
METHODS: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM.
RESULTS: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%-40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization.
CONCLUSIONS: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.
D H Pfizenmaier, F O Al Atawi, Y Castillo, K Chandrasekaran, L T Cooper
Predictors of left ventricular dysfunction in patients with Takayasu's or giant cell aortitis.
Clin Exp Rheumatol. 2004;22(6 Suppl 36):S41-5.
Abstract/Text
OBJECTIVES: The aim of this study was to determine the clinical and angiographic predictors of left ventricular systolic dysfunction (LVSD) from a relatively large and angiographically characterized Takayasu's or Giant Cell aortitis (TA/GCA) population.
BACKGROUND: LVSD in patients with TA/GCA has been described in case reports and attributed variously to hemodynamic and immunologic factors. The predictors of LVSD in patients with angiographically confirmed TA/GCA are not known.
METHODS: We identified 78 patients with angiographically confirmed TA/ GCA that underwent transthoracic echocardiography (TTE) at Mayo Clinic. Echocardiograms were then reviewed independently by reviewers blinded to clinical and angiographic data. LVSD was defined as an ejection fraction (LVEF) less than 50%.
RESULTS: The study population was 84% Caucasian (54/78), 91% female (58/78), and had a mean age of disease onset of 30 years (+/- 15 years). LVSD was present in 14 of 78 patients (18%) with TA/GCA. The mean LVEF in the LVSD group (n = 14) was 37% +/- 7%, compared to an LVEF of 62% +/- 6% (p < 0.0001) in those without LVSD (n = 64). LVSD was not associated with hypertension or aortic regurgitation (p > 0.5). However, LVSD was found in 43% (9/21) of patients with aortic arch involvement, versus only 9% (5/57) of patients without aortic arch involvement (p = 0.0013). Patients with LVSD had a median of 2 (range 1-4) involved aortic segments compared to a median of 1 (range 1-4) among those without LVSD (p = 0.013).
CONCLUSIONS: In TA/GCA aortitis, LVSD is associated with involvement of the aortic arch and with the greater extent of aortic involvement. The hemodynamic variables, aortic regurgitation and systemic hypertension, were not associated with LVSD, consistent with reports that cardiac inflammation is responsible for LVSD in a majority of cases. Ours is the first study to estimate an incidence of LVSD in patients with TA/GCA aortitis, which was 18%.
S Hiramitsu, S Morimoto, S Kato, A Uemura, N Kubo, K Kimura, A Sugiura, T Itoh, H Hishida
Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study.
Jpn Circ J. 2001 Oct;65(10):863-6.
Abstract/Text
The present study was designed to determine whether the wall thickening seen in acute myocarditis is caused by interstitial edema. The study group comprised 25 patients (idiopathic myocarditis, 17; eosinophilic myocarditis, 8) in whom acute myocarditis was diagnosed histologically and who underwent echocardiography and endomyocardial biopsy during both the acute and convalescent phases. The following echocardiographic parameters were measured: interventricular septum and left ventricular posterior wall thickness, left ventricular end-diastolic dimension, and left ventricular ejection fraction. Based on the myocardial biopsy specimens, the degree of interstitial edema was classified into 3 grades [(-), 1(+), 2(+)] and the transverse diameter of cardiac myocytes was measured using light microscopy. The thickness of both the interventricular septum and left ventricular wall decreased from 14.3+/-3.7 mm and 13.3+/-2.4 mm in the acute phase to 9.7+/-1.7 mm (p<0.001) and 10.2+/-1.7 mm (p<0.0001), respectively, in the convalescent phase. Edema was present in 22 patients (88.0%) in the acute phase, but in the convalescent phase, edema was present in only 7 patients (28.0%), indicating a significant reduction in the degree of edema (p<0.0001). Cardiac myocyte diameter did not differ significantly between the acute (13.6+/-1.1 microm) and convalescent (13.8+/-1.8 microm) phases.
Hiroto Aota, Hiroyuki Yamamoto, Jun Isogai, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Takahiro Tanaka
Case Report: Acute Eosinophilic Myocarditis With a Low-Flow Heart Failure With Preserved Ejection Fraction Phenotype.
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.
Shinya Hiramitsu, Shin-ichiro Morimoto, Shigeru Kato, Akihisa Uemura, Masatsugu Ohtsuki, Yasuchika Kato, Atsushi Sugiura, Kenji Miyagishima, Nami Mori, Ryuji Yoda, Kazumasa Mori, Masatsugu Iwase, Hitoshi Hishida
Significance of transient left ventricular wall thickening in acute lymphocytic myocarditis.
Heart Vessels. 2007 Jan;22(1):25-9. doi: 10.1007/s00380-006-0933-1. Epub 2007 Jan 26.
Abstract/Text
Transient left ventricular (LV) wall thickening is observed in patients with acute lymphocytic myocarditis. The present study was undertaken to clarify the significance of transient LV wall thickening in patients with this disease. The subjects comprised 25 patients with acute lymphocytic myocarditis. Echocardiography was used to measure the thickness of the interventricular septum (IVS) and the LV posterior wall (PW) at four time points after myocarditis onset--namely, on days 1-3, 6-8, 13-15, and 28-30--to clarify the timing and frequency of wall thickening. The 25 patients were divided into a fulminant myocarditis group (n = 14) and a nonfulminant myocarditis group (n = 11), and the relationship between LV wall thickening and myocarditis severity was investigated. Left ventricular wall thickening was greatest on days 1-3 after myocarditis onset (IVS: 13.3 +/- 3.2 mm; PW: 12.1 +/- 2.6 mm), with this finding being noted in 14 of the 25 cases (56%). By days 6-8, the thickness of IVS had virtually normalized to 10.6 +/- 1.6 mm (P < 0.0001) and that of PW to 10.2 +/- 1.4 mm (P = 0.0006). The thickness of the IVS and PW on days 1-3 after myocarditis onset were 14.6 +/- 3.7 and 13.0 +/- 2.9 mm, respectively, in the fulminant group (P = 0.014), and 11.5 +/- 0.9 and 10.9 +/- 1.4 mm, respectively, in the nonfulminant group (P = 0.039). In lymphocytic myocarditis, LV wall thickening is greatest on days 1-3 after myocarditis onset and improves to near normal by days 6-8. Such transient LV wall thickening occurs in approximately 50% of cases. Left ventricular wall thickening was more marked in the fulminant compared with the nonfulminant group.
B Pinamonti, E Alberti, A Cigalotto, L Dreas, A Salvi, F Silvestri, F Camerini
Echocardiographic findings in myocarditis.
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.
G M Felker, J P Boehmer, R H Hruban, G M Hutchins, E K Kasper, K L Baughman, J M Hare
Echocardiographic findings in fulminant and acute myocarditis.
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.
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
Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.
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").
Vanessa M Ferreira, Jeanette Schulz-Menger, Godtfred Holmvang, Christopher M Kramer, Iacopo Carbone, Udo Sechtem, Ingrid Kindermann, Matthias Gutberlet, Leslie T Cooper, Peter Liu, Matthias G Friedrich
Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations.
J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
Abstract/Text
This JACC Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation (Lake Louise Criteria) that include options to use parametric mapping techniques. While each parameter may indicate myocardial inflammation, the authors propose that CMR provides strong evidence for myocardial inflammation, with increasing specificity, if the CMR scan demonstrates the combination of myocardial edema with other CMR markers of inflammatory myocardial injury. This is based on at least one T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted CMR images), with at least one T1-based criterion (increased myocardial T1, extracellular volume, or late gadolinium enhancement). While having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one (i.e., T2-based OR T1-based) marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, albeit with less specificity. The update is expected to improve the diagnostic accuracy of CMR further in detecting myocardial inflammation.
Copyright © 2018. Published by Elsevier Inc.
Hiroyuki Yamamoto, Marie Takahashi, Jun Isogai
A case of vaccine-associated myocarditis following pneumococcal immunization leading to acute mitral regurgitation.
ESC Heart Fail. 2022 Jun;9(3):2013-2019. doi: 10.1002/ehf2.13881. Epub 2022 Mar 14.
Abstract/Text
Vaccine-associated myocarditis (VAM) is a rare entity but can result in potentially serious sequelae if left untreated. However, the mechanisms of the complications of VAM and its treatment remain unclear. Herein, we report the first case of VAM related to pneumococcal immunization, presenting as a local and systemic inflammatory reaction, in which the patient developed significant secondary mitral regurgitation, resulting in acute heart failure. Finally, the patient recovered completely following corticosteroid treatment. This case highlights the value of cardiac magnetic resonance and the pitfall of endomyocardial biopsy in establishing the definitive diagnosis of VAM and emphasizes the importance of optimal management in understanding the mechanism and instituting the treatment for secondary mitral regurgitation caused by VAM.
© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Ingrid Kindermann, Christine Barth, Felix Mahfoud, Christian Ukena, Matthias Lenski, Ali Yilmaz, Karin Klingel, Reinhard Kandolf, Udo Sechtem, Leslie T Cooper, Michael Böhm
Update on myocarditis.
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.
Hassan Abdel-Aty, Philipp Boyé, Anja Zagrosek, Ralf Wassmuth, Andreas Kumar, Daniel Messroghli, Petra Bock, Rainer Dietz, Matthias G Friedrich, Jeanette Schulz-Menger
Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches.
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.
Anthony H Aletras, Peter Kellman, J Andrew Derbyshire, Andrew E Arai
ACUT2E TSE-SSFP: a hybrid method for T2-weighted imaging of edema in the heart.
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.
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
Presentation, patterns of myocardial damage, and clinical course of viral myocarditis.
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.
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
Cardiac MR With Late Gadolinium Enhancement in Acute Myocarditis With Preserved Systolic Function: ITAMY Study.
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.
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.
Ali Yilmaz, Ingrid Kindermann, Michael Kindermann, Felix Mahfoud, Christian Ukena, Anastasios Athanasiadis, Stephan Hill, Heiko Mahrholdt, Matthias Voehringer, Michael Schieber, Karin Klingel, Reinhard Kandolf, Michael Böhm, Udo Sechtem
Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance.
Circulation. 2010 Aug 31;122(9):900-9. doi: 10.1161/CIRCULATIONAHA.109.924167. Epub 2010 Aug 16.
Abstract/Text
BACKGROUND: Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin.
METHODS AND RESULTS: In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; P<0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (P=0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV- and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement.
CONCLUSIONS: Both LV-EMB and RV-EMB are safe procedures if performed by experienced interventionalists. The diagnostic yield of EMB may be optimized when samples from both ventricles are available. Preferential biopsy in regions showing late gadolinium enhancement on cardiovascular magnetic resonance does not increase the number of positive diagnoses of myocarditis.
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
Complications of 2-D echocardiography guided transfemoral right ventricular endomyocardial biopsy.
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.
Shigeru Kato, Shin-Ichiro Morimoto, Shinya Hiramitsu, Akihisa Uemura, Masatsugu Ohtsuki, Yasuchika Kato, Kenji Miyagishima, Yukihiko Yoshida, Shuji Hashimoto, Hitoshi Hishida
Risk factors for patients developing a fulminant course with acute myocarditis.
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.
S C Smith, J H Ladenson, J W Mason, A S Jaffe
Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates.
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.
Mototsugu Nishii, Takayuki Inomata, Hitoshi Takehana, Ichiro Takeuchi, Hironari Nakano, Toshimi Koitabashi, Jun-ichi Nakahata, Naoyoshi Aoyama, Tohru Izumi
Serum levels of interleukin-10 on admission as a prognostic predictor of human fulminant myocarditis.
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.
W M Franz, A Remppis, R Kandolf, W Kübler, H A Katus
Serum troponin T: diagnostic marker for acute myocarditis.
Clin Chem. 1996 Feb;42(2):340-1.
Abstract/Text
J Soongswang, K Durongpisitkul, A Nana, D Laohaprasittiporn, C Kangkagate, K Punlee, N Limpimwong
Cardiac troponin T: a marker in the diagnosis of acute myocarditis in children.
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.
河村慧四郎、北浦泰、出口宏章、他. 厚生省特定疾患特発性心筋症調査研究班病因分科会：ウイルス性あるいは特発性心筋炎に関する全国アンケート調査、第3報－昭和57年度および昭和60年度における調査の集計－厚生省特定疾患特発性心筋症調査研究班 昭和60年度研究報告集 1986:23-36.
M Kodama, H Oda, M Okabe, Y Aizawa, T Izumi
Early and long-term mortality of the clinical subtypes of myocarditis.
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.
R E McCarthy, J P Boehmer, R H Hruban, G M Hutchins, E K Kasper, J M Hare, K L Baughman
Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis.
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.
Yasuhide Asaumi, Satoshi Yasuda, Isao Morii, Hiroyuki Kakuchi, Yoritaka Otsuka, Atsushi Kawamura, Yoshikado Sasako, Takeshi Nakatani, Hiroshi Nonogi, Shunichi Miyazaki
Favourable clinical outcome in patients with cardiogenic shock due to fulminant myocarditis supported by percutaneous extracorporeal membrane oxygenation.
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.
日本循環器学会他：不整脈非薬物治療ガイドライン（2018 年改訂版）（日本循環器学会/日本不整脈心電学会合同ガイドライン）．https://www.j-circ.or.jp/cms/wp-content/uploads/2018/07/JCS2018_kurita_nogami191120.pdf.
日本循環器学会他：2021年 JCS/JHRS ガイドライン フォーカスアップデート版 不整脈非薬物治療（日本循環器学会/日本不整脈心電学会合同ガイドライン）．https://www.j-circ.or.jp/cms/wp-content/uploads/2021/03/JCS2021_Kurita_Nogami.pdf.
日本循環器学会他：2021年JCS/JHFS ガイドライン フォーカスアップデート版 急性・慢性心不全診療（日本循環器学会/日本心不全学会合同ガイドライン）．https://www.j-circ.or.jp/cms/wp-content/uploads/2021/03/JCS2021_Tsutsui.pdf.
Barry J Maron
Sudden death in young athletes.
N Engl J Med. 2003 Sep 11;349(11):1064-75. doi: 10.1056/NEJMra022783.
Abstract/Text
A E Cabinian, R J Kiel, F Smith, K L Ho, R Khatib, M P Reyes
Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model.
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)
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
Fulminant eosinophilic myocarditis associated with visceral larva migrans caused by Toxocara canis infection.
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.
L T Cooper, G J Berry, R Shabetai
Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators.
N Engl J Med. 1997 Jun 26;336(26):1860-6. doi: 10.1056/NEJM199706263362603.
Abstract/Text
BACKGROUND: Idiopathic giant-cell myocarditis is a rare and frequently fatal disorder. We used a multicenter data base to define the natural history of giant-cell myocarditis and the effect of treatment.
METHODS: We identified 63 patients with idiopathic giant-cell myocarditis through journal announcements and direct mailings to cardiovascular centers worldwide.
RESULTS: The patients consisted of 33 men and 30 women with an average age of 42.6 years; 88 percent were white, 5 percent were black, 5 percent were Southeast Asian or Indian, and 2 percent were Middle Eastern. Most presented with congestive heart failure (47 patients, or 75 percent), ventricular arrhythmia (9 patients, or 14 percent), or heart block (3 patients, or 5 percent), although in some cases the initial symptoms resembled those of acute myocardial infarction (4 patients). Nineteen percent had associated autoimmune disorders. The rate of survival was worse than among 111 patients with lymphocytic myocarditis in the Myocarditis Treatment Trial (P<0.001); among our patients, the rate of death or cardiac transplantation was 89 percent, and median survival was only 5.5 months from the onset of symptoms. The 22 patients treated with corticosteroids and cyclosporine, azathioprine, or both therapies survived for an average of 12.3 months, as compared with an average of 3.0 months for the 30 patients who received no immunosuppressive therapy (P=0.001). Of the 34 patients who underwent heart transplantation, 9 (26 percent) had a giant-cell infiltrate in the transplanted heart and 1 died of recurrent giant-cell myocarditis.
CONCLUSIONS: Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. Patients usually die of heart failure and ventricular arrhythmia unless cardiac transplantation is performed. Despite the possibility of fatal disease recurrence, transplantation is the treatment of choice for most patients.
J W Mason, J B O'Connell, A Herskowitz, N R Rose, B M McManus, M E Billingham, T E Moon
A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators.
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.
A Samuelsson, T L Towers, J V Ravetch
Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor.
Science. 2001 Jan 19;291(5503):484-6. doi: 10.1126/science.291.5503.484.
Abstract/Text
The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcgamma receptor-humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Fc receptor, FcgammaRIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of FcgammaRIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.
Shigeru Kato, Shin-ichiro Morimoto, Shinya Hiramitsu, Akihisa Uemura, Masatsugu Ohtsuki, Yasuchika Kato, Kenji Miyagishima, Nami Mori, Hitoshi Hishida
Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis.
Heart Vessels. 2007 Jan;22(1):48-51. doi: 10.1007/s00380-006-0923-3. Epub 2007 Jan 26.
Abstract/Text
A 45-year-old man developed fulminant myocarditis for which ventricular assist devices (intra-aortic balloon pumping and percutaneous cardiopulmonary support) were required for hemodynamic support. Echocardiography showed left ventricular akinesis and, since no improvement was noted on the following day, immunoglobulin (70 g/day for 2 days) was added to the therapy. The left ventricular ejection fraction increased to 25% and 40% at 12 and 36 h, respectively, representing a marked improvement in wall motion within a very short period. An endomyocardial biopsy specimen revealed focal lymphomononuclear infiltrate with adjacent myocytolysis, and acute lymphocytic myocarditis was diagnosed. Two days after administration of immunoglobulin, the serum level of interleukin-6 decreased rapidly from 180 to 5.9 pg/ml. In this patient, cardiac function improved immediately after immunoglobulin administration, suggesting the usefulness of this therapy. Three years after the diagnosis the patient is in good health, with steady normal left ventricular ejection fraction. We conclude that there are cases of acute myocarditis in which high-dose intravenous immunoglobulin therapy is effective.
Andrea Frustaci, Cristina Chimenti, Fiorella Calabrese, Maurizio Pieroni, Gaetano Thiene, Attilio Maseri
Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders.
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.
日本循環器学会他：急性・慢性心不全診療ガイドライン （2017年版）．https://www.j-circ.or.jp/cms/wp-content/uploads/2017/06/JCS2017_tsutsui_h.pdf.
Saeko Yoshizawa, Tomoko Sugiyama Kato, Donna Mancini, Charles C Marboe
Characteristics of patients with advanced heart failure having eosinophilic infiltration of the myocardium in the recent era.
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.
G S Spear
Eosinophilic explant carditis with eosinophilia: ?Hypersensitivity to dobutamine infusion.
J Heart Lung Transplant. 1995 Jul-Aug;14(4):755-60.
Abstract/Text
BACKGROUND: Eosinophilic carditis with peripheral eosinophilia has been observed in a number of clinical situations. This report describes this association in patients undergoing heart transplantation and offers a possible explanation.
METHODS: The clinical records and explanted hearts of 31 consecutive patients who received primary orthotopic heart transplants were reviewed. Clinical features particularly analyzed included the following: age, cardiac status and assistance devices, catheterizations, medical or surgical disorders including parasites, tryptophane exposure, medications, and peripheral blood counts. Pathologic features particularly studied included the following: dilatation and hypertrophy, fibrosis, mural thrombi, carditis, eosinophils, myocardial necrosis, vasculitis, valvular disease, and coronary artery disease. Prior endomyocardial biopsy specimens were also reviewed.
RESULTS: Seven patients had eosinophilic carditis compatible with hypersensitivity carditis. Eight had eosinophilia. All patients with carditis received intravenous dobutamine (Dobutrex solution) continuously for more than 1 month immediately preceding transplantation. All patients with eosinophilia received intravenous dobutamine continuously for 15 days or longer and exhibited eosinophilia only during dobutamine therapy with the exception of one patient in whom eosinophilia was observed 8 days after cessation of 8 days of therapy. Among 13 patients who received dobutamine for more than a month immediately before transplantation, nine had eosinophilic carditis, peripheral eosinophilia, or both.
CONCLUSIONS: Prolonged continuous intravenous administration of dobutamine was associated with eosinophilic carditis and eosinophilia. No other clinical factor with a relationship to either eosinophilia or carditis was identified. The responsible agent may have been a preservative in the dobutamine solution, sodium bisulfite.
Koshiro Kanaoka, Kenji Onoue, Satoshi Terasaki, Tomoya Nakano, Michikazu Nakai, Yoko Sumita, Kinta Hatakeyama, Fumio Terasaki, Rika Kawakami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Yoshihiko Saito, Japanese Registry of Fulminant Myocarditis Investigators
Features and Outcomes of Histologically Proven Myocarditis With Fulminant Presentation.
Circulation. 2022 Nov 8;146(19):1425-1433. doi: 10.1161/CIRCULATIONAHA.121.058869. Epub 2022 Sep 27.
Abstract/Text
BACKGROUND: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence.
METHODS: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis.
RESULTS: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion (<40%) on admission, and ventricular tachycardia or fibrillation on admission day were associated with worse 90-day survival. Severe histologic damage (damaged cardiomyocytes comprising ≥50% of the total cardiomyocytes) was associated with a worse 90-day prognosis in patients with lymphocytic myocarditis.
CONCLUSIONS: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP.
REGISTRATION: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000039763.
Michela Brambatti, Maria Vittoria Matassini, Eric D Adler, Karin Klingel, Paolo G Camici, Enrico Ammirati
Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes.
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.
Nicola L Diny, Noel R Rose, Daniela Čiháková
Eosinophils in Autoimmune Diseases.
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.
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
Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy.
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.
Takafumi Koyama, Hiroyuki Yamamoto, Manabu Matsumoto, Jun Isogai, Tadashi Isomura, Shinji Tanaka
Late-Stage Löffler's Endocarditis Mimicking Cardiac Tumor: A Case Report.
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.
Hiroyuki Yamamoto, Toru Hashimoto, Keiko Ohta-Ogo, Hatuse Ishibashi-Ueda, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Tomoki Yokochi
A case of biopsy-proven eosinophilic myocarditis related to tetanus toxoid immunization.
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.
Ken-Ei Sada, Koichi Amano, Ritei Uehara, Masahiro Yamamura, Yoshihiro Arimura, Yoshikazu Nakamura, Hirofumi Makino, Research Committee on Intractable Vasculitides, the Ministry of Health, Labour, Welfare of Japan
A nationwide survey on the epidemiology and clinical features of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) in Japan.
Mod Rheumatol. 2014 Jul;24(4):640-4. doi: 10.3109/14397595.2013.857582. Epub 2013 Dec 2.
Abstract/Text
OBJECTIVE: We conducted a cross-sectional nationwide survey to determine eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) prevalence and clinical features in Japan.
METHODS: Data for EGPA patients in 2008 were collected from 1,564 hospitals. In total, 965 patients were reported from 365 departments. In a second survey, clinical data for 473 patients were obtained.
RESULTS: We estimated that 1,866 (95% CI: 1,640-2,092) patients have EGPA in Japan (prevalence, 17.8/1,000,000). Of the 473 patients in the second survey, 315 fulfilled American College of Rheumatology (ACR) criteria or Lanham's criteria for EGPA. The mean age (± SD) of the 315 at onset was 55 ± 14 years, male to female ratio 1:2. 93% of patients had neurological manifestations, which were the organ system most frequently involved. Among 277 patients tested for myeloperoxidase (MPO)-/p anti-neutrophil cytoplasmic antibody (ANCA), 139 (50%) were positive, while only 6 of 238 were positive for proteinase3 (PR3)-/cANCA. MPO-ANCA-positive patients had renal involvement, mucous membrane or ophthalmological symptoms, and ENT symptoms more frequently, whereas cutaneous lesions and cardiovascular involvement were less common.
CONCLUSION: The prevalence of EGPA and the frequency of MPO-/p-ANCA-positivity in Japanese EGPA patients were mostly similar to those of Western countries. However, female predominance and a high frequency of neurological manifestations characterized Japanese patients.
I Puljiz, A Beus, I Kuzman, S Seiwerth
Electrocardiographic changes and myocarditis in trichinellosis: a retrospective study of 154 patients.
Ann Trop Med Parasitol. 2005 Jun;99(4):403-11. doi: 10.1179/136485905X36307.
Abstract/Text
The frequencies of electrocardiographic (ECG) abnormalities and myocarditis were determined, retrospectively, among 154 cases of trichinellosis [101 males and 53 females, with a mean (S.D.) age of 35.60 (14.64) years] who were hospitalized at the University Hospital for Infectious Diseases in Zagreb, Croatia, over a 5-year period. Eighty-seven (56%) of the patients, most of them in the invasive phase of infection with Trichinella spiralis, were found to have abnormalities when examined by 12-lead, resting electrocardiography. The ECG disorder most frequently observed was a non-specific ventricular repolarization disturbance (with ST-T wave changes), followed by bundle-branch conduction disturbances, and sinus tachycardia. The other ECG disorders recorded, during various phases of the infection, were sinus bradycardia, right bundle-branch block, supraventricular and ventricular extrasystoles, low-voltage QRS complexes in standard limb leads, first-degree atrio-ventricular block, and atrial fibrillation. Eighteen (12%) of the patients were identified as cases of myocarditis (13 in the invasive phase and five in the convalescent) and two (1.3%) as cases of myopericarditis. One patient developed acute myocardial infarction 28 days after the onset of disease and died soon thereafter; an autopsy revealed multiple necroses and fibroses of the myocardium and thrombus of a coronary artery. Although ECG abnormalities appear to be a common feature of trichinellosis, especially during the invasive phase of the disease, they are rarely associated with a poor prognosis. A transient, non-specific, ventricular-repolarization disturbance is the abnormality most commonly observed.
Rekha Mankad, Crystal Bonnichsen, Sunil Mankad
Hypereosinophilic syndrome: cardiac diagnosis and management.
Heart. 2016 Jan;102(2):100-6. doi: 10.1136/heartjnl-2015-307959. Epub 2015 Nov 13.
Abstract/Text
Hypereosinophilic syndrome (HES) is a heterogeneous group of conditions that is defined at its core by hypereosinophilia (HE) (blood eosinophil count of >1.5×10(9)/L) and organ damage directly attributable to the HE. Cardiac dysfunction occurs frequently in all forms of HES and is a major cause of morbidity and mortality. Once a significantly elevated eosinophil count is identified, it must be confirmed on repeat testing and the aetiology for the HE must be rigorously sought out with a focus on identifying whether organ dysfunction is occurring. Echocardiography is routinely performed to assess for cardiac involvement, looking for evidence of left ventricular and/or right ventricular apical obliteration or thrombi or a restrictive cardiomyopathy. Cardiac magnetic resonance imaging and CT are often useful adjuncts to establish the diagnosis but endomyocardial biopsy remains the gold standard. To decrease the degree of eosinophilia, treatment can include corticosteroids and/or imatinib based on the aetiology. Anticoagulation, standard heart failure therapy for a restrictive cardiomyopathy and finally cardiac transplantation may be indicated in the treatment algorithm.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
H Yamamoto, S Nakatani, K Hashimura
Löffler's endomyocarditis.
Heart. 2005 Feb;91(2):135. doi: 10.1136/hrt.2004.041558.
Abstract/Text
NSFとガドリニウム造影剤使用に関する合同委員会（日本医学放射線学会・日本腎臓学会）：腎障害患者におけるガドリニウム造影剤使用に関するガイドライン（第2版：2009年9月2日改訂）．https://jsn.or.jp/news/NSFguideline090902.pdf.
Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous M-H, Sheikh J, Simon D, Simon H-U, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol [Internet]. 2009 Dec [cited 2019 Feb 26];124(6):1319-1325.e3. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0091674909014109
Hidetomo Maruyoshi, Satoshi Nakatani, Yoshio Yasumura, Akihisa Hanatani, Tomoyoshi Yamaguchi, Chikao Yutani, Hatsue Ishibashi-Ueda, Kunio Miyatake, Masakazu Yamagishi
Löffler's endocarditis associated with unusual ECG change mimicking posterior myocardial infarction.
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.
S Hayashi, M Isobe, Y Okubo, J Suzuki, Y Yazaki, M Sekiguchi
Improvement of eosinophilic heart disease after steroid therapy: successful demonstration by endomyocardial biopsied specimens.
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.
Mizuhiro Arima, Tatsuji Kanoh, Yasunobu Kawano, Tetsuya Oigawa, Shinichiro Yamagami, Shigeru Matsuda
Serum levels of eosinophil cationic protein in patients with eosinophilic myocarditis.
Int J Cardiol. 2002 Jul;84(1):97-9.
Abstract/Text
C H Kim, R E Vlietstra, W D Edwards, G S Reeder, G J Gleich
Steroid-responsive eosinophilic myocarditis: diagnosis by endomyocardial biopsy.
Am J Cardiol. 1984 May 15;53(10):1472-3.
Abstract/Text
Y Uetsuka, S Kasahara, N Tanaka, M Sekiguchi, M Hiroe, Z X Yu, S Hosoda
Hemodynamic and scintigraphic improvement after steroid therapy in a case with acute eosinophilic heart disease.
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.
Enrico Ammirati, Manlio Cipriani, Marzia Lilliu, Paola Sormani, Marisa Varrenti, Claudia Raineri, Duccio Petrella, Andrea Garascia, Patrizia Pedrotti, Alberto Roghi, Edgardo Bonacina, Antonella Moreo, Maurizio Bottiroli, Maria P Gagliardone, Michele Mondino, Stefano Ghio, Rossana Totaro, Fabio M Turazza, Claudio F Russo, Fabrizio Oliva, Paolo G Camici, Maria Frigerio
Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.
Circulation. 2017 Aug 8;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386. Epub 2017 Jun 2.
Abstract/Text
BACKGROUND: Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM.
METHODS: The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis.
RESULTS: In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (P<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank P<0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; P<0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, P=0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ≥55% at discharge had a significant decrease in LVEF at follow-up.
CONCLUSIONS: Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.
© 2017 American Heart Association, Inc.
Riina Kandolin, Jukka Lehtonen, Kaisa Salmenkivi, Anne Räisänen-Sokolowski, Jyri Lommi, Markku Kupari
Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression.
Circ Heart Fail. 2013 Jan;6(1):15-22. doi: 10.1161/CIRCHEARTFAILURE.112.969261. Epub 2012 Nov 13.
Abstract/Text
BACKGROUND: Giant-cell myocarditis often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. Current therapy rests on multiple-drug immunosuppression but its prognostic influence remains poorly known. We set out to analyze (1) our experience in diagnosing giant-cell myocarditis and (2) the outcome of patients on combined immunosuppression.
METHODS AND RESULTS: We reviewed the histories, diagnostic procedures, details of treatment, and outcome of 32 consecutive patients with histologically verified giant-cell myocarditis treated in our hospital since 1991. Twenty-six patients (81%) were diagnosed by endomyocardial or surgical biopsies and 6 at autopsy or post-transplantation. Twenty-eight (88%) patients underwent endomyocardial biopsy. The sensitivity of transvenous endomyocardial biopsy increased from 68% (19/28 patients) to 93% (26/28) after up to 2 repeat procedures. The 26 biopsy-diagnosed patients were treated with combined immunosuppression (2-4 drugs) including cyclosporine in 20 patients. The Kaplan-Meier estimates of transplant-free survival from symptom onset were 69% at 1 year, 58% at 2 years, and 52% at 5 years. Of the transplant-free survivors, 10/17 (59%) experienced sustained ventricular tachyarrhythmias during follow-up and 3 received intracardiac defibrillator shocks for ventricular tachycardia or fibrillation.
CONCLUSIONS: Repeat endomyocardial biopsies are frequently needed to diagnose giant-cell myocarditis. On contemporary immunosuppession, two thirds of patients reach a partial clinical remission characterized by freedom from severe heart failure and need of transplantation but continuing proneness to ventricular tachyarrhythmias.
Leslie T Cooper, Joshua M Hare, Henry D Tazelaar, William D Edwards, Randall C Starling, Mario C Deng, Santosh Menon, G Martin Mullen, Brian Jaski, Kent R Bailey, Madeleine W Cunningham, G William Dec, Giant Cell Myocarditis Treatment Trial Investigators
Usefulness of immunosuppression for giant cell myocarditis.
Am J Cardiol. 2008 Dec 1;102(11):1535-9. doi: 10.1016/j.amjcard.2008.07.041. Epub 2008 Sep 18.
Abstract/Text
Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 +/- 15 years, and the mean time from symptom onset to presentation was 27 +/- 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.
Vigyan Bang, Sarju Ganatra, Sachin P Shah, Sourbha S Dani, Tomas G Neilan, Paaladinesh Thavendiranathan, Frederic S Resnic, Thomas C Piemonte, Ana Barac, Rushin Patel, Ajay Sharma, Rohan Parikh, Ghulam M Chaudhry, Mark Vesely, Salim S Hayek, Monika Leja, David Venesy, Richard Patten, Daniel Lenihan, Anju Nohria, Leslie T Cooper
Management of Patients With Giant Cell Myocarditis: JACC Review Topic of the Week.
J Am Coll Cardiol. 2021 Mar 2;77(8):1122-1134. doi: 10.1016/j.jacc.2020.11.074.
Abstract/Text
Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Kaj Ekström, Jukka Lehtonen, Riina Kandolin, Anne Räisänen-Sokolowski, Kaisa Salmenkivi, Markku Kupari
Incidence, Risk Factors, and Outcome of Life-Threatening Ventricular Arrhythmias in Giant Cell Myocarditis.
Circ Arrhythm Electrophysiol. 2016 Dec;9(12). doi: 10.1161/CIRCEP.116.004559.
Abstract/Text
BACKGROUND: Ventricular tachyarrhythmias are characteristic of giant cell myocarditis, but their true incidence, predictors, and outcome are unknown.
METHODS AND RESULTS: Our work involved 51 patients with giant cell myocarditis (35 women) aged 52±12 years. Their medical records were reviewed for history, results of laboratory and imaging studies, and occurrence of serious cardiac events, including life-threatening ventricular tachyarrhythmias. Sudden cardiac death (fatal or aborted) was the primary end point of our analyses, whereas the composite of sudden cardiac death and ventricular tachycardia requiring treatment constituted the secondary end point. Giant cell myocarditis presented as nonfatal ventricular tachyarrhythmia in 10 patients and as a fatal cardiac arrest in 1 patient. Overall, 14 of 50 patients suffered a sudden cardiac death during follow-up, with a cumulative incidence of 22% at 1 year and 26% at 5 years from presentation. The composite incidence of sudden cardiac death or ventricular tachycardia was 41% at 1 year and 55% at 5 years. The incidence of arrhythmias was associated with high plasma concentrations of troponin-T and N-terminal brain natriuretic propeptide, as well as with moderate-to-severe fibrosis on myocardial biopsy and history of ventricular tachyarrhythmias at presentation (P<0.05 for all). An intracardiac cardioverter defibrillator was implanted in 31 patients, of whom 17 had altogether 114 appropriate antiarrhythmic therapies by the device and none suffered an arrhythmic death.
CONCLUSIONS: In giant cell myocarditis, the risk of life-threatening ventricular arrhythmias exceeds 50% at 5 years from admission, being related to the presenting clinical manifestation and markers of myocardial injury and scarring.
© 2016 American Heart Association, Inc.
Kaj Ekström, Jukka Lehtonen, Riina Kandolin, Anne Räisänen-Sokolowski, Kaisa Salmenkivi, Markku Kupari
Long-term outcome and its predictors in giant cell myocarditis.
Eur J Heart Fail. 2016 Dec;18(12):1452-1458. doi: 10.1002/ejhf.606. Epub 2016 Jul 13.
Abstract/Text
AIMS: There are no studies focusing on prognostic factors in giant cell myocarditis (GCM). We aimed to identify predictors of transplant-free survival in GCM.
METHODS AND RESULTS: We analysed the details of 46 patients with GCM (31 women, mean age 51 ± 12 years) seen at our hospital since 1991 and followed for the occurrence of cardiac death or transplantation till May 2015. The association of transplant-free survival with patient characteristics, laboratory data on admission, and myocardial histology in the 38 patients diagnosed prior to death or transplantation was examined. Altogether 26 patients died (n = 8) or underwent transplantation (n = 18) a median of 11 months following symptom onset. The 5-year estimate of transplant-free survival was 42% [95% confidence interval (CI) 35-48%]. By Cox regression analysis, the hazard ratio for death or transplantation was 0.87 (95% CI 0.75-0.99) per +5% difference in LVEF, 1.06 (95% CI 1.03-1.10) per + 1000 ng/L difference in NT-proBNP, and 4.57 (95% CI 1.63-11.28) for cardiac troponin-T above the median of 85 ng/L at presentation. The severity of necrosis and fibrosis in myocardial biopsy, graded by the consensus of two cardiac pathologists as none, mild, moderate, or severe, predicted the outcome with a hazard ratio of 7.17 (95% CI 2.29-22.40) for the presence of either necrosis or fibrosis of at least moderate extent.
CONCLUSIONS: In GCM, the probability of transplant-free survival is 42% at 5 years from symptom onset. Markers of myocyte injury and cardiac dysfunction help predict the outcome.
© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
日本循環器学会他：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）．p6-7 www.j-circ.or.jp/guideline/pdf/JCS2009_izumi_d.pdf.
Edwin A Burgstaler, Leslie T Cooper, Jeffrey L Winters
Treatment of chronic dilated cardiomyopathy with immunoadsorption using the staphylococcal A-agarose column: a comparison of immunoglobulin reduction using two different techniques.
J Clin Apher. 2007;22(4):224-32. doi: 10.1002/jca.20137.
Abstract/Text
Auto-antibodies to myocardial antigens have been implicated in the pathogenesis of chronic dilated cardiomyopathy (DCM). A protein A immunoadsorption affinity column system was used to remove IgG antibodies, particularly IgG3. Two techniques, the standard technique (T-1) used for removal of IgG Factor VIII inhibitors and a technique (T-2) designed to enhance IgG3 removal and address issues in venous access, minimize positive fluid balance, and adverse reactions were compared. A total of four patients were treated, two patients were treated for 5 consecutive days with each technique. T-2 resulted in larger, but not significantly so, IgG3 reduction (70% and 63%) than T-1 (53% and 59%). Both techniques lowered total IgG levels by >or=93%. Because of venous access problems, 60% of T-1 procedures reached the plasma volume target versus 100% for T-2. Positive fluid balance was significantly lower for T-2 (+507 +/- 465) ml versus T-1 (+2,206 +/- 724) ml. Overall adverse event (AE) rate (T-1:16, T-2:15) was similar between the techniques but demonstrated a statistically significant difference in the types of reactions that occurred. All AE were mild in nature, common to other apheresis procedures, and were easily managed. This small study, demonstrated that a modified technique (T-2) with superior fluid balance should be used when treating DCM with the Immunosorba system.
Keiko Ohta-Ogo, Yasuo Sugano, Soshiro Ogata, Takafumi Nakayama, Takahiro Komori, Kazuo Eguchi, Kaoru Dohi, Tetsuro Yokokawa, Hiromitsu Kanamori, Shigeyuki Nishimura, Kazufumi Nakamura, Yoshihiko Ikeda, Kunihiro Nishimura, Genzou Takemura, Toshihisa Anzai, Michiaki Hiroe, Kinta Hatakeyama, Hatsue Ishibashi-Ueda, Kyoko Imanaka-Yoshida
Myocardial T-Lymphocytes as a Prognostic Risk-Stratifying Marker of Dilated Cardiomyopathy - Results of the Multicenter Registry to Investigate Inflammatory Cell Infiltration in Dilated Cardiomyopathy in Tissues of Endomyocardial Biopsy (INDICATE Study).
Circ J. 2022 Jun 24;86(7):1092-1101. doi: 10.1253/circj.CJ-21-0529. Epub 2022 Mar 10.
Abstract/Text
BACKGROUND: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13-24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up.
CONCLUSIONS: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.
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.
B Pitt, F Zannad, W J Remme, R Cody, A Castaigne, A Perez, J Palensky, J Wittes
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.
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.
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
Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.
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
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)
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).
Eur Heart J. 2008 Oct;29(19):2388-442. doi: 10.1093/eurheartj/ehn309. Epub 2008 Sep 17.
Abstract/Text
Jie Xiao, Miho Shimada, Wenling Liu, Dayi Hu, Akira Matsumori
Anti-inflammatory effects of eplerenone on viral myocarditis.
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.
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
Eplerenone in patients with systolic heart failure and mild symptoms.
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.).
Ingrid Kindermann, Michael Kindermann, Reinhard Kandolf, Karin Klingel, Burkhard Bültmann, Thomas Müller, Angelika Lindinger, Michael Böhm
Predictors of outcome in patients with suspected myocarditis.
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.
