The prognosis of patients depends of course on clinical presentation, NYHA class [164], the severity of systolic dysfunction of left or right ventricle, ECG finding in which prolongation of QRS complex was put in association with higher risk of mortality or heart transplant [103], and it depends also on the levels of laboratory parameters [139] – troponin, BNP etc. [26, 110, 111, 112]. Prognosis is usually good in patients with the mild course of the disease and with preserved LV EF [165].

There were described as prognostically significant also cardiac MRI findings (specifically LGE), [27] and EMB results [164].

Authors of the opening picture: National Institutes of Health (NIH); NIAID; Patrick J. Lynch; Departmenf of Radiology of the 2nd Medical School and Motol Hospital; Kalumet

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References:

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

27) GRÜN, S., SCHUMANN J. a et al. Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis: Predictors of Mortality and Incomplete Recovery. JACC. 2012, 59(18), 1604-1615.

49) OKURA a et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. Journal of the American College of Cardiology [online]. 2003, 41(2), 322 [cit. 2017-02-05].

55) T., JR., COOPER a et al. IDIOPATHIC GIANT-CELL MYOCARDITIS — NATURAL HISTORY AND TREATMENT. The New England Journal of Medicine. 1997, 1997(336), 1860-1866.

56) KANDOLIN a et al. Diagnosis, Treatment, and Outcome of Giant-Cell Myocarditis in the Era of Combined Immunosuppression. Circulation: Heart Failure [online]. 2013, 2013(6), 15-22 [cit. 2017-02-05].

60) KANDOLIN. Cardiac Sarcoidosis: Epidemiology, Characteristics and Outcome over 25 Years in a Nationwide Study. Circulation [online]. 2014, 2014(-), 1-35 [cit. 2017-02-05].

72) M., FELKER a et al. Underlying Causes and Long-Term Survival in Patients with Initially Unexplained Cardiomyopathy. The New England Journal of Medicine [online]. 2000, 342(-), 1077-1084 [cit. 2017-02-05].

73) F., CURRIE a et al. Heart muscle disease related to HIV infection: prognostic implications. BMJ [online]. 1994, 309(1605), – [cit. 2017-02-05].

74) D., FISHER a et al. Mild dilated cardiomyopathy and increased left ventricular mass predict mortality: The Prospective P2C2 HIV Multicenter Study. America Heart Journal [online]. 2005, 150(3), 439–447 [cit. 2017-02-05].

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

103) UKENA, CH. a et al. Prognostic electrocardiographic par ametersin patients with suspected myocarditis. European Journal of Heart Failure [online]. 2011, 13(-), 398-405 [cit. 2017-02-27].

110) TEELE, S.A. Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis. The Journal of Pediatrics. 2011, 158(4), 638-643.

111) LAUER, B. a et al. Cardiac Troponin T in Patients With Clinically Suspected Myocarditis. JACC. 1997, 30(5), 1354-1359.

112) AL-BILTAGI, M. Circulating cardiac troponins levels and cardiac dysfunction in children with acute and fulminant viral myocarditis. Acta Pediatrica. 2010, 99(-), 1510-1516.

139) Kapitola 22.5.1. Myokarditidy. In: ASCHERMANN, M., ed. Kardiologie. Praha: Galén, 2004. pp. 840-845. ISBN 80-7262-290-0.

164) KINDERMANN, I. a et al. Predictors of Outcome in Patients With Suspected Myocarditis. Circulation [online]. 2008, 118(6), 639-648 [cit. 2017-02-28].

165) BLAUWET, L. a et al. Progress in Cardiovascular Diseases. 2010, 52(-), 274-288.

Příspěvek Prognosis pochází z Myokarditida

Specifically, in ECMO, a relatively high efficiency was proved in studies with both children and adults [110, 158, 159, 160]. In a multicentric study with 255 children with myocarditis [158] in which ECMO therapy was indicated, 61 % (155 children) lived to be discharged from the hospital. Remaining 100 cases included cases of children who were disconnected from ECMO, but afterward, they died, or multiorgan failure developed or they underwent a heart transplant. Complications during the ECMO therapy (renal dysfunction and arrhythmias) and female gender were marked as a predictor of mortality in this study.

In a study of 75 adult and children patients (with the representation of 32 %) the survival probability reached 64 %. There were also described some predictors of mortality, specifically renal dysfunction, neurological complications and the situation when even after 48 hours after the connection to ECMO, troponin T level did not reach its peak [159].

Survival rate when ECMO was indicated in other studies reached also levels around 70 % [110, 160]. In the last-mentioned study, there was investigated also the psychological development of patients after ECMO therapy. One-third of patients stated anxiety, depression or posttraumatic stress disorder.

The heart transplant is indicated just in cases of advanced heart disease accompanied by considerable symptomatology of a patient when there are exhausted all possibilities of pharmacological and non-pharmacological therapy [16, 26, consultation with Assoc. prof. Kuchynka, M.D., Ph.D.].

In 2013 [161], there was published a work evaluating the incidence of acute rejection and survival rate in patients after a heart transplant as a result of lymphocytic myocarditis, idiopathic DCMP or ischemic CMP with the aim to compare its results with the conclusions of previously performed studies pointing at the high risk of acute rejection in patients with myocarditis [162]. Statistically significant incidence [161] of acute rejection was described in the group with suffered lymphocytic myocarditis until two years after the heart transplant in comparison with the group of patients with ischemic CMP (specifically 3,8 % of patients in “myocarditis-group” in comparison with 05 % in “ischemic CMP group”).

Worldwide, approximately 45 % of the heart transplants are performed because of idiopathic DCMP and 8 % because of myocarditis [162]. In the Czech Republic, DCMP is the most frequent cause of heart transplant, specifically in 49,2 % [163].

Author of the opening picture: Patrick J. Lynch

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References:

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

110) TEELE, S.A. Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis. The Journal of Pediatrics. 2011, 158(4), 638-643.

217) JCS Joint Working Group. Guidelines for Diagnosis and Treatment of Myocarditis (JCS 2009). Circulation Journal. 2011, 75(-), 734-743.

158) RAJAGOPAL, S. a et al. Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: A review of the Extracorporeal Life Support Organization registry. Crit Care Med. 2010, 38(2), 328-327.

159) HSU, K.H. a et al. Extracorporeal membranous oxygenation support for acute Fulminant myocarditis: analysis of a single center’s experience. European Journal of Cardio-thoracic Surgery. 2011, 40(-), 682-688.

160) Outcomes, long-term quality of life, and psychologic assessment of fulminant myocarditis patients rescued by mechanical circulatory support.: Abstract. Critical Care Medicine [online]. 2011, 39(5), 1029-1035 [cit. 2017-02-28].

161) YOSHIZAWA, S. a et al. Outcome of Patients Having Heart Transplantation for Lymphocytic Myocarditis. The American Journal of Cardiology. 2013, 112(-), 405-410.

162) MOLONEY, E.D. a et al. Transplantation for myocarditis: a controversy revisited. J Heart Lung Transplant. [online]. 2005, 24(8), 1103-1110 [cit. 2017-02-28].

163) Indikace k ortotopické transplantaci srdce. PIRK, J., I. MÁLEK a et al. Transplantace srdce. Praha: Nakladatelství Karolinum, 2008, s. 72-74. ISBN 978-80-246-1606-3.

Příspěvek Mechanical support of inner organs and heart transplant pochází z Myokarditida

The use of this therapy is considered in ICMP with induced autoimmune reaction and with the production of anti-myocardial autoantibodies [24, 98, 99]. The principle of the therapy lies in the removal of circulating autoantibodies of IgG class circulating in peripheral blood [99]. Its efficiency has been already confirmed, however, just in small groups of patients [98]. Currently, a multicentric randomized study is taking place with the aim to verify the efficiency of the therapy in 200 patients with DCMP [152]. Already performed studies stated a favorable effect on cardiac function and on the decrease of NT-pro BNP levels in serum [153]. A study from 2009 did not prove the improvement of the LV EF, however, it described the improvement of the parameters from bicycle ergometry [153].

Interferons

Antiviral therapy with interferon beta proved in several studies a favorable effect on cardiac function and symptomatology of patients, however just in myocarditis cases caused by enteroviruses and adenoviruses [154, 156]. In a study from 2003, 22 patients were treated with subcutaneously administered interferon beta for 24 weeks whereas, in all of them, EMB proved the presence of enteroviruses or adenoviruses [154]. After 6 months, improvement of the heart function was observed in 14 patients and moreover, control EMB did not prove the presence of previously discovered viral agents in all of these patients. The fact that in 7 patients, there was observed no significant improvement of the heart function, was in some references and in the study, put in connection with a significant left ventricular dysfunction at the beginning of the therapy. Thus, the results in these patients could be influenced even by the extent of the inflammation, myocardial damage and by viral load in the myocardium and by the long-term duration of symptoms [23].

In 2009, there were published the results of a multicentric randomized and placebo-controlled study of 143 patients with chronic viral cardiomyopathy [155] and the detection of enteroviruses, adenoviruses or PBV19 in the myocardium, that supports in many respects the results of the study from 2003. In the group treated with interferon beta, there was observed an improvement of the heart function and even decrease of the viral load.

Author of the opening picture: Nevit Dilmen

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References:

23) SCHULTHEISS, Heinz-Peter, Uwe KÜHL a Leslie T. COOPER, JR. The management of myocarditis. European Heart Journal. 2011, 32(-), 2616–2625.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

152) Multicenter Study of Immunoadsorption in Dilated Cardiomyopathy. Clinical Trials [online]. -: -, 2007 [cit. 2017-02-28].

153) DOESCH, A.O. a et al. Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy: Abstract. Journal of Clinical Apheresis [online]. 2009, 24(4), 141-149 [cit. 2017-02-28].

154) KÜHL, U. a et al. Interferon-β Treatment Eliminates Cardiotropic Viruses and Improves Left Ventricular Function in Patients With Myocardial Persistence of Viral Genomes and Left Ventricular Dysfunction. Circulation [online]. 2003, 107(22), 2793- [cit. 2017-02-28].

155) SCHULTHEISS, H.P. a et al. Late-Breaking Clinical Trial Abstracts From the American Heart Association’s Scientific Sessions 2008: The Effect of Subcutaneous Treatment with Interferon-Beta-1b Over 24 Weeks on Safety, Virus Elimination and Clinical Outcome in Patients with Chronic Viral Cardiomyopathy. 2008, 118(22), 2310-2317.

156) SCHMIDT-LUCKE, C. a et al. Interferon Beta Modulates Endothelial Damage in Patients with Cardiac Persistence of Human Parvovirus B19 Infection. The Journal of Infectious Diseases [online]. 2010, 201(6), 936-945 [cit. 2017-02-28].

Příspěvek Immunoadsorption and interferons pochází z Myokarditida

One of the first large studies dealing with the issue of efficiency of immunosuppressive therapy in myocarditis – Myocarditis Treatment Trial from 1995 [11] did not prove a beneficial effect of this therapy on cardiac function and prognosis. By contrast, 4-year-mortality rate was 56 %. Many references questioned the fact that EMB samples were evaluated just with histopathological criteria and that there was not evaluated the presence of an agent in the myocardium what could according to the references negatively influence the disease course and prognosis in those patients that were classified in the group treated with immunosuppressants [140].

This conclusion is supported even by the research from 2003 [149] in patients with acute lymphocytic myocarditis treated with immunosuppressive therapy. In patients who responded to the therapy, left ventricular EF improvement was observed (in average from original 25 % on 47 %). In “non-responding patients”, the state of health was either constant or they underwent heart transplant or died. Retrospective investigation proved in 85 % of “non-responding” patients the presence of a viral agent in the myocardium what was, on the other hand, proved in just 14 % of “responding” patients (in all cases it was hepatitis C virus) and moreover, in 90 % of them, anti-myocardial autoantibodies were detected. The conclusion of the study was that immunosuppressive therapy is beneficial in patients with the absence of a viral agent in the myocardium and in those with the production of autoantibodies.

The role of immunosuppressive therapy is investigated even in patients with ICMP. The first randomized study dealing with the issues of efficiency of this therapy specifically in ICMP was performed in 2001 and an interesting fact is that patients were involved in this study on the basis of the presence of higher HLA expression [150]. In this study, there was no difference between the group treated with placebo and group treated with immunosuppressants in the question of mortality, but in the group treated with immunosuppressive therapy, NYHA class and heart function improvement (LV EF, LV EDD, and other parameters) was observed. After three months, in this group, the improvement of the state of health was observed in 71,8 % of patients (when compared with placebo group – 20,9 %). The conclusion of the study was that even a short-time therapy with immunosuppressants (90-100 days on the basis of the medicament) may bring long-term beneficial effect.

The last published study dealing with this issue is from the year 2009 [151]. In the group of patients with immunosuppressive therapy and negative detection of a virus in the myocardium, the improvement of LV EF, EDV, ESV, LV EDD and NYHA class was observed in 88 % of patients. Remaining 12 % of patients in this group showed the constant state of health what could be explained by the fact that there could be present an agent in the myocardium, which was not concluded in PCR panel or there were present mechanisms which are not sensitive to immunosuppressive therapy.

Currently, a study comparing the therapeutic schemes of both above-mentioned studies [150, 151] in patients with myocarditis is taking place [99].

Author of the opening picture: SubDural12

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References:

11) O´CONNELL, J. B., A. HERSKOWITZ a et al. A Clinical Trial of Immunosuppressive Therapy for Myocarditis. New England Journal of Medicine. 1995, -(333), 269-275.

55) T., JR., COOPER a et al. IDIOPATHIC GIANT-CELL MYOCARDITIS — NATURAL HISTORY AND TREATMENT. The New England Journal of Medicine. 1997, 1997(336), 1860-1866.

76) Srdce a systémová onemocnění. ECardio.cz [online]. -: -, – [cit. 2017-02-05].

77) ZHANG a et al. Lupus Myocarditis: A Case–Control Study from China. Chin Med J (Engl) [online]. 2015, 128(19), 2588-2594 [cit. 2017-02-05].

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

140) PALEČEK, T. Inflammatory cardiomyopathy: Still many questions await answers. Cor et Vasa. 2013, 55(-), E341-E344.

149) Immunosuppressive Therapy for Active Lymphocytic Myocarditis: Virological and Immunologic Profile of Responders Versus Nonresponders. Circulation [online]. 2003, 107(6), 857-863 [cit. 2017-02-28].

150) WOJNICZ, R. a et al. Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy. Circulation [online]. 2001, 104(1), 39-45 [cit. 2017-02-28].

151) FRUSTACI, A. a et al. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. European Heart Journal [online]. 2009, 30(16), 1995-2002 [cit. 2017-02-28].

Příspěvek Immunosuppressive therapy pochází z Myokarditida

The favorable effect of IVIG in recently developed DCMP and myocarditis in adults was described even in work from 1997 [145] when the improvement of left ventricular EF from 24 on 41 % generally was observed in patients. However, it was not a randomized study. On the other hand, a multicentric randomized study of the same author from 2001 with patients with new-onset DCMP in which an inflammatory infiltrate was present in 16 % of patients did not prove such effect in adults. Both placebo and IVIG group registered similar left ventricular EF improvement [146]. However, in the case of this study, there was marked as a limitation that just a small part of patients has histopathological evidence of an inflammation and that immunochemical analysis of bioptically taken samples of the myocardium was not performed [146, 147]. In more recent retrospective studies, a favorable effect of IVIG was proved in adult patients with fulminant myocarditis or ICMP when in a study from 2008 [147] it led to the average improvement of the left ventricular EF by 30 %. However, it was a small study. Another study from 2014 [148] was also retrospective, but with a larger group of patients and results were compared with a control group. In the IVIG group, the therapy led to the improvement of the left ventricular EF and reduction of the development of arrhythmias. However, for the reason that an effect of IVIG was not proved clearly by large multicentric randomized studies, their routine use in the acute phase of the disease in adult patients is not recommended, because according to the references, other necessary multicentric randomized studies have not been performed yet [24]. However, it the same reference it is stated that “IVIG has no major side-effects,” what was proved by studies [141, 143, 144], “and may be used in myocarditis refractory to conventional heart failure therapy, both viral and autoimmune forms, particularly if autoantibody-mediated.” [24] Thus, therapy with IVIG still remains not quite clearly and convincingly proved by evidence in the literature.

However, in children and teenagers, in contrast to adults, the situation is the opposite. A positive influence on the heart function and 1-year-survival rate was proved in children receiving high doses of IVIG [144] and in indicated cases they are administered even in routine practice because they are connected with better course and prognosis of the disease and there is described even the effect that they could prevent the progress of myocarditis into chronic phase [102].

Authors of the opening picture: Database Center for Life Science -DBCLS

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References:

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

102) STARÁ, V. Nestrukturální srdeční onemocnění u dětí. Vox Pediatriae. 2006, 6(4), 26-32.

141) GULLESTAD, L. a et al. Immunomodulating Therapy With Intravenous Immunoglobulin in Patients With Chronic Heart Failure. Circulation [online]. 2001, 103(2), 220-225 [cit. 2017-02-27].

142) DENNERT, R. a et al. Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load. Antiviral Therapy [online]. 2010, 15(-), 193-201 [cit. 2017-02-27].

143) BHATT, G.C. a et al. Use of Intravenous Immunoglobulin Compared With Standard Therapy is Associated With Improved Clinical Outcomes in Children With Acute Encephalitis Syndrome Complicated by Myocarditis. Pediatr Cardiol. 2012, 33(-), 1370-1376.

144) DRUCKER, N.A. a et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation [online]. 1994, 89(1), 252-257 [cit. 2017-02-27].

145) MCNAMARA, D.M. a et al. Intravenous Immune Globulin in the Therapy of Myocarditis and Acute Cardiomyopathy. Circulation [online]. 1997, 95(11), 2476-2478 [cit. 2017-02-28].

146) MCNAMARA, D.M. a et al. Controlled Trial of Intravenous Immune Globulin in Recent-Onset Dilated Cardiomyopathy. Circulation [online]. [cit. 2017-02-28].

147) GOLAND, S. a et al. Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: Series of six patients and review of liter Can J Cardiol. [online]. 2008, 24(7), 571-574 [cit. 2017-02-28].

148) YU, D.Q. a et al. Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study. Exp Ther Med. [online]. 2014, 7(1), 97-102 [cit. 2017-02-28].

Příspěvek Immunoglobulines pochází z Myokarditida

Author of the opening picture: part of the web template

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References:

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

42) L., BAUGHMAN. Diagnostika myokarditidy: Dallaským kritériím odzvonilo. Circulation-CZ. 2006, 5(1), 7-9.

140) PALEČEK, T. Inflammatory cardiomyopathy: Still many questions await answers. Cor et Vasa. 2013, 55(-), E341-E344.

Příspěvek Immunological therapy generally pochází z Myokarditida

Treatment with antivirotics has according to the references in the majority of patients very limited importance. Their positive effect was documented primarily in patients treated with antivirotics in the initial phase of a viral infection [139]. A limiting factor is also an amount of possible unfavorable side affects of some antivirotics and the fact that most patients do not arrive in the specialized cardiological center in the phase of viremia [99]. According to the references, antivirotics may be considered as a therapeutic option in patients in which the heart failure therapy did not lead to the left ventricular function improvement or as a medication to the reduction of heart failure symptomatology [99].

Author of the opening picture: MarinaVladivostok

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References:

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

139) Kapitola 22.5.1. Myokarditidy. In: ASCHERMANN, M., ed. Kardiologie. Praha: Galén, 2004. pp. 840-845. ISBN 80-7262-290-0.

Příspěvek Treatment with ATB and antivirotics pochází z Myokarditida

There are no specific recommendations even for treatment of thromboembolism in myocarditis and thus it follows recommendations of cardiological societies. Increased risk of thromboembolism is for example in eosinophilic myocarditis. Japanese Circulation Society even recommends the use of anticoagulants in eosinophilic myocarditis and a prevention of thromboembolism [127].

Author of the opening picture: Jer5150

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References:

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

57) A., CHAUDHRY a et al. Modern day management of giant cell myocarditis. International Journal of Cardiology. 2015, 2015(178), 82-84.

62) H., BIRNIE a et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis. Heart Rhythm. 2014, 11(7), 1304–1323.

92) JR., RASSI a et al. Chagas disease. Lancet. 2010, 375(-), 1388-1402.

93) H., MALIK a et al. The Epidemiology, Clinical Manifestations, and Management of Chagas Heart Disease. Clin. Cardiol. 2015, 38(9), 565-569.

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

127) JCS Joint Working Group. Guidelines for Diagnosis and Treatment of Myocarditis (JCS 2009). Circulation Journal. 2011, 75(-), 734-743.

Příspěvek Treatmenf of arrhythmias and thromboembolism pochází z Myokarditida

The basis of the therapy is ACE-inhibitors, eventually sartans, beta-blockers (in acute phase administered after the stabilization of a patient´s state of health), diuretics and antagonist of mineralocorticoid receptors [24, 26, 98, 99, 100]. To sustain the adequate cardiac output, dopamine or dobutamine is indicated in some cases [102].

ACE-inhibitors disturb the effect of angiotensin-converting enzyme which transforms biologically inactive angiotensin I into biologically active angiotensin II which increases, by binding on its receptors, among others the system blood pressure. Sartans are blockers of the receptor for angiotensin II and are indicated in patients with the intolerance of ACE-inhibitors [130].

In treatment with ACE-inhibitors and sartans, besides their cardiological effect, there is described even a positive influence on the inflammatory reaction, cardiac remodelation and progression of myocarditis in DCMP, respectively ICMP [131, 132]. In mouse models, administration of captopril and losartan led to a significant reduction of inflammatory damage to the myocardium [131]. However, more distinct reduction of inflammation, necrosis, severity and incidence of myocarditis was observed in mice receiving captopril. The reduction of inflammatory reaction could be according to the study´s conclusions caused by the reduction of local inflammatory reaction and thus by the decreased amount of T lymphocytes involving in the inflammation. The direct mechanism is however still not quite clear.

Therapy with beta-blockers should be according to the recommendations initiated after the stabilization of a patient´s state of health [99]. By contrast, in later phases, it is described positive effect of specific beta-blockers on prognosis and inflammatory reaction. In a study comparing the effect of carvedilol, metoprolol and propranolol, carvedilol had positive effects on almost all researched parameters. It decreased not just the severity of myocarditis, but also mRNA expression of inflammatory cytokines [132]. Two other beta-blockers did not have any or just minor influence. By contrast, in another study with mice infected with Coxsackie B3 virus, a negative influence of administration of metoprolol on the myocarditis prognosis in the acute phase was observed [133]. In mice treated with metoprolol, the research proved increased viral replication, necrosis and inflammation. The mortality rate of mice in this group was 60 % higher than in a control group.

The most commonly indicated diuretics are loop diuretics which inhibit the transport of sodium and chloride ions in the loop oh Henle [134]. A Japanese study with mice models proved positive effect of Torasemide on myocardial fibrosis and remodelation [135]. Favourable influence on the myocardial fibrosis was put in connection with the decrease of levels of TNF beta1, collagen III and aldosterone synthetases and possible influence on the activity of angiotensin II and aldosterone.

Favourable effect on the myocardial remodelation was proved even at antagonist of aldosterone eplerenone [136] and at some calcium channel blockers, which are not however recommended in the therapy of acute heart failure [43, 93]. A similar effect was described even at ivabradine which reduced mortality in mice models by more than 30 % and reduced also the extent of fibrosis, expression of pro-inflammatory cytokines TNF alpha, IL-1beta and IL-6 and led to the improvement of the left ventricular function and to the normalization of its dimensions [137].

The indication of digoxin is full of contradiction in the case of acute heart failure in myocarditis. According to the references, its indication is documented just in some specific cases, however, on the other hand, a Japanese study from 1999 proved a negative influence of digoxin on viral myocarditis in mice models when it increased the extent of the myocardial necrosis and fibrosis [138].

Author of the opening picture: Benjah-bmm27.

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References:

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

102) STARÁ, V. Nestrukturální srdeční onemocnění u dětí. Vox Pediatriae. 2006, 6(4), 26-32.

130) Kapitola 13: Antihypertenziva – léčiva ovlivňující systém renin-angiotenzin-aldosteron. In: SLÍVA, J. a M. VOTAVA. Farmakologie. Praha: Triton, 2011. pp. 79-85. ISBN 978-80-7387-500-8.

131) BAHK, T.J. a et al. Comparison of Angiotensin Converting Enzyme Inhibition and Angiotensin II Receptor Blockade for the Prevention of Experimental Autoimmune Myocarditis. Int J Cardiol. [online]. 2008, 125(1), 85-93 [cit. 2017-02-27].

132) YUAN, Z. a et al. Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with antioxidant property. American Journal of Physiology [online]. 2004, 286(1), H83-H90 [cit. 2017-02-27].

133) REZKALLA, S. a et al. Effect of Metoprolol in Acute Coxsackievirus B3 Murine Myocarditis. JACC [online]. 1988, 12(2), 412-414 [cit. 2017-02-27].

134) Kapitola 12: Diuretika. In: SLÍVA, J. a M. VOTAVA. Farmakologie. Praha: Triton, 2011. pp. 127-130. ISBN 978-80-7387-500-8.

135) VEERAVEEDU, P.T. a et al. Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy. European Journal of Pharmacology. 2008, 581(-), 121-131.

136) JIE, X. a et al. Anti-inflammatory effects of eplerenone on viral myocarditis. European Journal of Heart Failure [online]. 2009, 11(-), 349-353 [cit. 2017-02-27].

137) YUE-CHUN, L. a et al. The Protective Effects of Ivabradine in Preventing Progression from Viral Myocarditis to Dilated Cardiomyopathy: Article 408. Frontiers in Pharmacology. 2016, 7(-), 1-10.

138) MATSUMORI, A. a et al. High Doses of Digitalis Increase the Myocardial Production of Proinflammatory Cytokines and Worsen Myocardial Injury in Viral Myocarditis: A Possible Mechanism of Digitalis Toxicity. Jpn Circ J [online]. 1999, 63(-), 934-940 [cit. 2017-02-27].

Příspěvek Heart failure therapy pochází z Myokarditida

Authors of the opening picture: own resource and Database Center for Life Science -DBCLS

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References:

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

128) MARON, B.J. a et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. JACC [online]. 2005, 45(8), 1340-1345 [cit. 2017-02-27].

129) CABINIAN, A.E. a et al. Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model: Abstract. J Lab Clin Med. [online]. 1990, 115(4), 454-462 [cit. 2017-02-27].

Příspěvek Regime measures pochází z Myokarditida

From the point of view of causal therapy, an important obstacle is a vast number of different agents of myocarditis and ICMP. Their spectrum includes viral, bacterial and protozoal agents, autoimmune disorders and hypersensitive reactions to different medications, whereas the activity of these agents is not still completely known in many of them. Patients differ even in the disease course when myocarditis may progress in some of the cases even in ICMP what is influenced by the persistence of the agent in the myocardium, by the development of autoimmune reaction against components of cardiomyocytes, chronic inflammatory reaction in the heart muscle or by the combination of both above-mentioned factors (chapter Pathogenesis).

The disease heterogeneity is thus a limiting factor – from the point of view of manifestation and the course of examination findings and so even from the point of view of when myocarditis/ICMP was diagnosed and when the specific therapy was instituted. It is because, in a part of patients, myocarditis with a mild course do not have to be diagnosed and thus may be detected until the stage of ICMP [26].

The effectivity of therapy is influenced even by the extent of changes in the myocardium as a result of myocarditis, thus what is the degree of damage (fibrosis, necrosis) and what are regeneration possibilities of the myocardium [23].

Currently, the treatment of myocarditis and ICMP thus consists primarily of symptomatic and support therapy and physical activity restriction [24, 26]. In the therapy of heart failure and arrhythmias, there are used the procedures suggested by the European and American Society of Cardiology. The parts of the therapy are both pharmacological therapy and the use of ICD and mechanical organ support in the fulminant course of myocarditis [24, 98, 127]. Despite these facts, the treatment of heart failure in myocarditis and ICMP has some specifics. It is, for example, proved protective effect of some medicaments or their unfavorable impact on the prognosis.

Specific therapy, primarily immunosuppressive therapy, depends on the results of EMB. However, according to the references, in a large number of specific treatment procedures, other studies are necessary [24, 98].

Author of the opening picture: Madprime

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References:

23) SCHULTHEISS, Heinz-Peter, Uwe KÜHL a Leslie T. COOPER, JR. The management of myocarditis. European Heart Journal. 2011, 32(-), 2616–2625.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

127) JCS Joint Working Group. Guidelines for Diagnosis and Treatment of Myocarditis (JCS 2009). Circulation Journal. 2011, 75(-), 734-743.

Příspěvek Treatment generally pochází z Myokarditida

EMB is an invasive diagnostic method which is described in many references as a gold standard in the diagnosis of myocarditis and ICMP and which definitively confirms the diagnosis and has also an important role in the determination of the disease aetiology [24, 96, 98, 99, 100]. If myocarditis is not confirmed by EMB, it is called clinically suspect myocarditis [96]. In the statement of the European Society of Cardiology, it is even recommended that EMB should be considered in all patients with suspect myocarditis [24]. However, its indication still follows the recommendations of the American and European Society of Cardiology from the year 2007. It is recommended primarily in two clinical scenarios: “1. New-onset heart failure of less than 2 weeks’ duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise. 2. New-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks.” [123]. The reason for the indication is the exclusion of giant-cell or necrotizing eosinophilic myocarditis because of the specific therapy [16, 123]. It is often indicated also in “heart failure of more than 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks.” [123]. When inflammatory changes and non-presence of the agent are found in the myocardium, these patients may be treated with immunosuppressive therapy [29].

The reason for the establishment of these indication criteria was according to the references the absence of unified methodology of indication of this examination and also the fact that in a large part of patients (50 to 70 %) myocarditis heals up without any severe consequences for patients and the performance of EMB would not bring a change of the therapeutic strategy [8].

Even though it is an invasive method, there is described a relatively low incidence of severe complications, around 1 to 2 % [53]. It is a risk of the development of ventricular or supraventricular arrhythmias, damage to the mitral/tricuspid valve or ventricular perforation and the development of cardiac tamponade [53, 123]. Fatal complications were described just in a very small number of cases [124]. The examination specificity is even up to 100 %. The sensitivity varies widely according to the number of taken myocardial samples and the type of the present inflammation, for example for GCM it is 80 to 85 % [123, consultation with Assoc. prof. Kuchynka, M.D., Ph.D.]. The limited diagnostic utilization could be according to the references caused the fact that the myocardial inflammation may be of the focal character and that it is relatively often localized in the subepicardial area [24, 42]. Sensitivity was increased in some studies and case reports with electroanatomic mapping and CMRI for the more accurate localization of the inflammation [61, consultation with Adla, M.D].

The EMB itself is performed by a bioptome which is introduced in patient´s right/left/both ventricles via the right inner jugular vein in the case of the EMB from right ventricle or via the femoral artery in the EMB from left ventricle [100]. The examination is performed under fluoroscopic or ECHO control [125]. There are taken approximately 5 to 10 myocardial samples of a size of 1–2 mm³. Part of them is examined histopathologically (picture 12) and evaluated on the basis of the Dallas criteria. The criteria alone are however according to a number of references insufficient ([42], chapter Histopathology), and thus there are performed routinely even other examinations. It is primarily immunochemical analysis for the evaluation of the inflammatory infiltrate when different monoclonal and polyclonal antibodies are used for the detection of the infiltrate, for example, anti CD3 for the detection of T lymphocytes and anti CD68 for the detection of macrophages [98, 126]. HLA detection is also performed frequently [98, 126]. Myocarditis is confirmed by “the presence of ≥ 14 leukocytes per mm² of a bioptically taken sample of the myocardium including up to 4 monocytes or macrophages per mm² and ≥ 7 CD3+ T lymphocytes per mm²” [5]. According to the type of the infiltrate, myocarditis is characterized into lymphocytic, giant-cell, granulomatous and eosinophilic myocarditis [16, 38]. A part of the myocardial samples examination is aimed at the detection of the agent when it is aimed at pathogens described in chapter Serology. In the case of PVB19, it is recommended to determine the number of copies of the genetical viral material (called as viral load) for the evaluation of the relevance of the finding as a possible disease cause, because the role of PVB19 in aetiology of myocarditis was questioned partly [35]. According to some studies, the evaluation of the replication activity in the myocardium would be beneficial [100].

Picture 12: Histopathological picture of viral myocarditis after autopsy of a patient with the development of congestive heart failure  (autor KGH; https://commons.wikimedia.org/wiki/File:Viral_myocarditis_(1).JPG; https://commons.wikimedia.org/wiki/File:Viral_myocarditis_(2).JPG)

Nuclear methods and cardiac catheterization

Cardiac catheterization is based on the performance of selective coronarography to exclude ischemic heart disease as the cause of a patient´s symptoms. According to the references, other diagnostic relevance is not described [96, 100].

Nuclear methods are used primarily for the detection of cardiac sarcoidosis, primarily FDG PET scan which may detect active myocardial inflammation [50].

Author of the opening picture: KGH

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References:

5) MAISCH B., BÜLTMAN B., FACTOR S., GRÖNE H.-J. et al. World Heart Federation Consensus Conferences Definition of Inflammatory Cardiomyopathy (Myocarditis): Report from two Expert Committees on Histology and Viral Cardiomyopathy. Herz [online]. 2000, 25 (3), 200-209 [cit. 2016-08-26].

8) ZEMÁNEK D. Kapitola 15: Zánětlivé onemocnění myokardu. In: VESELKA, J. a V.ROHN. Kardiovaskulární medicína [online]. 1. vydání. Brno: Fasta Medica, 2015. ISBN 978-80-88056-00-3.

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

35) KUETHE, F., J. LINDNER a et al. Prevalence of Parvovirus B19 and Human Bocavirus DNA in the Heart of Patients with no Evidence of Dilated Cardiomyopathy or Myocarditis. Clinical Infectious Diseases. 2009, -(49), 1660-1666.

38) ŠTEINER, I. Kardiopatologie: pro patology i kardiology. Praha: Galén, 2010. ISBN 978-80-7262-672-4.

42) L., BAUGHMAN. Diagnostika myokarditidy: Dallaským kritériím odzvonilo. Circulation-CZ. 2006, 5(1), 7-9.

50) KUBÁNEK a VOSKA L. Obrovskobuněčná myokarditida a sarkoidóza srdce – update 2015. Kardiologická revue – Interní medicína. 17(4), 295-299.

53) K., BENNETT a et al. Evaluation of the Role of Endomyocardial Biopsy in 851 Patients With Unexplained Heart Failure From 2000–2009. Circulation: Heart Failure [online]. 2013, 2013(6), 676-684 [cit. 2017-02-05].

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

123) COOPER, L.T., Jr. a et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease. JACC. 2007, 50(19), 1914-1931.

124) DECKERS, J.W. a et al. Complications of Transvenous Right Veatricular Endomyocardial Biopsy in Adult Patients With Cardiomyopathy: A Seven-Year Survey of 546 Consecutive Diagnostic Procedures in a Tertiary Referral Center. JACC [online]. 1992, 19(1), 43-47 [cit. 2017-02-27].

125) FROM, A.M. a et al. Current Status of Endomyocardial Biopsy. Mayo Clin Proc. [online]. 2011, 86(11), 1095-1102 [cit. 2017-02-27].

126) LEONE, O. a et al. 2011 Consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovascular Pathology. 2012, 21(-), 254-274.

Příspěvek Endomyocardial biopsy (EMB) and nuclear methods and cardiac catheterization pochází z Myokarditida

Biomarkers of the myocardial necrosis and heart failure

There are several biomarkers of the myocardial necrosis used in clinical practice – levels of troponin T or I, creatine kinase (CK), primarily its myocardial form (CK-MB), alternatively of myoglobin [26]. As a biomarker of heart failure, detection of natriuretic B peptides (BNP) or their prohormone (pro-BNP) is used.

Level of troponin in serum was in the case of myocarditis/ICMP in several studies established as a useful indicator of prognosis, mortality risk and of the extent of the myocardial damage [26, 109, 111, 112, 169]. Its sensitivity for the detection of myocarditis was in one study 53 % and specificity was up to 94 % [111]. Higher level was detected primarily in fulminant and fatal myocarditis cases [112]. A low troponin elevation was often detected even when the EMB result was negative. It could probably come in the situation when mild forms of inflammation with localized myocardial damaged are not caught by the EMB. On the contrary, the troponin level in serum was often in reference values even when there was a bioptical confirmation of myocarditis [111]. Elevation of troponin is detected approximately in 33 to 50 % of patients [43]. When comparing with the myocardial infarction, in myocarditis, it is common that it can be detected for a longer period of time and that its decrease is slower [99]. Troponin may be positive even several weeks from the initial manifestation of the disease.

CK and CK-MB are together with troponin and myoglobin other biomarkers of the myocardial damage, even though their detection in myocarditis was in some studies much lower than in troponin. In an American study [111], when troponin I elevation was proved in 53 % of patients, higher levels of CK and CK-MB were detected just in 8 % or 2 % respectively. On the other hand, CK-MB level higher than 29,5 ng/ml was marked as a mortality indicator with the sensitivity 83 % and specificity 73 % [26].

Natriuretic peptides have similar to troponin diagnostical and prognostic value in the case of development of heart failure [113] and determine its severity. Even in myocarditis, high level of BNP is described as a predictor of a worse prognosis and higher mortality [114].

Biomarkers of inflammation

Nonspecific markers of inflammation – leucocytosis, higher CRP levels, and erythrocytes sedimentation rate may be present in myocarditis and ICMP, however, they have love specificity in their diagnosis [26, 43]. Leucocytosis is for example detected in just 20 to 25 % of patients [43]. In differential count, most frequently, there are higher levels of lymphocytes and neutrophils, alternatively of eosinophils in eosinophilic myocarditis [43, 102].

Autoantibodies

In patients with myocarditis and/or DCMP, there have been discovered a large number of antibodies specific for myocarditis/DCMP [24]. Their testing is even recommended by the European Society of Cardiology [24]. Considering a vast number of identified autoantibodies, there are described in this chapter just some of them, primarily those marked as cardiac and specific for myocarditis/DCMP or as negative predictors [24].

It is for example detection of cardiac autoantibodies of IgG class in up to 59 % of patients with myocarditis and 20 % of patients with idiopathic DCMP [115] when according to the resources this finding identifies patients in which the cardiac dysfunction is a result of the immune system activity. Different anti-sarcolemma antibodies and even organ non-specific antibodies were represented in varying degrees in patients with myocarditis in another study [116]. In this study, the level of antibodies against sarcolemma of cardiomyocytes corresponded with the extent of cytolytic damage of the myocardium.

Further, the detection of beta-adrenergic antibodies was described by a number of studies in both patients with myocarditis and with DCMP [24]. In patients with DCMP, their positivity was connected with distinctively worse left ventricular function [117].

Alike beta-adrenergic autoantibodies, even antibodies against alpha/beta-myosin [24, 118], troponin I and T [24, 119] etc. were marked as negative predictors. List of other antibodies may be found in these references [24], [120].

Microbiology and serology

Routine serological examination of antibodies against the agent of myocarditis is not, with a few exceptions, recommended in the present [24]. In the Czech Republic, there are usually examined just antibodies against HIV, hepatitis viruses and Borrelia burgdorferi [24, 99].

A research from 2011 proved that viral serology has in the diagnosis of myocarditis only 9 % sensitivity and 77 % specificity [108].

Possibilities of serological examination are complicated by a lot of factors including primarily the incidence of viruses associated with myocarditis in the population, and the delay between the viral infection and performed serological examination [21]. Even under these circumstances, the isolation of a virus or direct detection of the virus is sometimes described as a useful diagnostic tool which points to a viral infection [121].

When investigating the aetiology of myocarditis and ICMP, primarily samples from EMB are used when some agents are examined with PCR (in the Czech Republic most frequently herpes simplex virus, EBV, CMV, HHV-6, Coxsackie, echoviruses, adenoviruses, PVB19 and Borrelia burgdorferi), [28, 99]. Other methods may be electron microscopy or in situ hybridization [98].

Others

Even other substances have been described as predictors of a higher risk of mortality in myocarditis – Fas ligand and IL-10 (together with other cytokines described in chapter Pathogenesis), [26]. In a study of children patients, higher levels of lactate, creatinine, and AST have been associated with higher mortality [110]. Some already implemented researches of myocarditis described different transcription of some genes and changes in the levels of specific miRNA [100, 122] where there is described their influence on both inflammatory activity (and so on the heart function) and on viral activity [122] within the meaning of inhibition and “support.” They are described not just as a possible diagnostic tool, however also as a potential therapy aim what has already been researched in several studies with positive results [122].

Author of the opening picture: Thomas Splettstoesser

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References:

21) ELAMM, Chantal, DeLisa FAIRWEATHER a Leslie T. COOPER. Pathogenesis and diagnosis of myocarditis. Heart. 2012, – (-), -.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

28) KREJČÍ, J., P. HUDE a et al. Endomyokardiální biopsie u recentní dilatační kardiomyopatie – zhodnocení vstupních charakteristik prvních padesáti nemocných. Cor et Vasa. 2011, -(53), 623-629.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

102) STARÁ, V. Nestrukturální srdeční onemocnění u dětí. Vox Pediatriae. 2006, 6(4), 26-32.

108) MAHDOUD, F. a et al. Virus serology in patients with suspected myocarditis: utility or futility? European Heart Journal. 2011, 32(-), 897-903.

109) BRAUNWALD, E. Biomarkers in Heart Failure. The New England Journal of Medicine. 2008, 358(-), 2148-2159.

110) TEELE, S.A. Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis. The Journal of Pediatrics. 2011, 158(4), 638-643.

111) LAUER, B. a et al. Cardiac Troponin T in Patients With Clinically Suspected Myocarditis. JACC. 1997, 30(5), 1354-1359.

112) AL-BILTAGI, M. Circulating cardiac troponins levels and cardiac dysfunction in children with acute and fulminant viral myocarditis. Acta Pediatrica. 2010, 99(-), 1510-1516.

113) JANUZZI, J.L., MANN, D.L. Chapter 23: Clinical Assessment of Heart Failure. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medicine. Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 473-483. ISBN 978-1-4557-5133-4.

114) ZHANG, CH. a et al. [Prognostic value of brain natriuretic peptide in people with viral myocarditis].: Abstract. Chinese Journal of Experimental and Clinical Virology [online]. 2012, 26(2), 125-126 [cit. 2017-02-27].

115) NEUMANN, D.A. a et al. Circulating Heart-Reactive Antibodies in Patients With Myocarditis or Cardiomyopathy. JACCC. 1990, 16(4), 839-846.

116) B. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis. Clin. exp. Immunol. 1982, 48(-), 533-545.

117) JAHNS, R. a et al. Autoantibodies Activating Human β1-Adrenergic Receptors Are Associated With Reduced Cardiac Function in Chronic Heart Failure. Circulation [online]. 1999, 99(5), 649-654 [cit. 2017-02-27].

118) LAUER, B. a et al. Antimyosin Autoantibodies Are Associated With Deterioration of Systolic and Diastolic Left Ventricular Function in Patients With Chronic Myocarditis. JACC. 2000, 35(1), 11-18.

119) HIRVELÄ, J.-L. a et al. Development of troponin autoantibodies in experimental coxsackievirus B3 myocarditis. European Journal of Clinical Investigation. 2009, 39(6), 457-462.

120) CAFORIO, A.L.P. a et al. Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity. 2008, 41(1), 35-45.

121) CALABRESE, F. a et al. Yocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects. Cardiovascular Research [online]. 2003, 60(-), 11-25 [cit. 2017-02-27].

122) HEYMANS, S. a et al. The Quest for New Approaches in Myocarditis and Inflammatory Cardiomyopathy. JACC. 2016, 68(21), 2348-2364.

169) AGEWALL, S. a et al. Troponin elevation in coronary vs. non-coronary disease. European Heart Journal [online]. 2011, 32(4), 404-411 [cit. 2017-02-28].

Příspěvek Laboratory examination pochází z Myokarditida

For the evaluation of myocardial oedema, T2 sequences are used, when the area of myocardial oedema has higher signal intensity than surrounding tissue [106]. However, there are described numerous difficulties when using this sequence, e.g. lower imaging quality, artifacts that may distort the results and that in the case of the diffuse myocardial damage, oedema does not have to be displayed sufficiently [106]. Thus, the ratio of values of the myocardial signal intensity (SI) and skeletal muscle signal intensity is used for the diagnosis of oedema. This ration is called oedema ratio (ER).

Hyperaemia is detected by T1 sequences. The principle of this CMRI part is a comparison of the myocardial SI before and immediately after the administration of a contrast agent what is then called as EGE (early gadolinium enhancement), Similar to T2 sequences, the comparison of the myocardial and skeletal muscles SI is used for the diagnosis of hyperaemia [106].

An important part of this examination is the evaluation of LGE (late gadolinium enhancement) which proves myocardial necrosis or in later phases fibrosis of the myocardium because gadolinium passes just through the membrane of damaged cardiomyocytes [106]. Most frequently, LGE is localized in the left ventricular free wall (often lateral) or in interventricular septum in subepicardial and/or midmyocardial layer [99, 100, 106], (Pic. 11). Subendocardial localization is described in ischemic myocardial damage [106]. The necrosis/fibrosis area may be a potential arrhythmogenic substrate [106].

To increase the utilization of the examination, Lake Louise Criteria have been created (Table 3) which describes besides above-mentioned procedures even possible indications and criteria for the confirmation of the diagnosis of myocarditis according to CMRI [107].

Picture 11: CMRI of a 17-year-old male with the 2^nd attack of myocarditis, distinct chest pain, elevation of troponin and increasing CRP. CMRI with the presence of LGE (red arrows) in acute phase of myocarditis and 6 months later again with the presence of LGE (Department of Radiology of the 2^nd Medical School and Motol Hospital, by Adla M.D.)

.

Picture 13: 15-year-old male with chronic myocarditis (inflammatory infectious cardiomyopathy). Aetiology unknown, did not prove even by endomyocardial biopsy. On the MRI scan, apperant a distinctive dilatation and dysfunction of both ventricles. LV EF 21 % (norm > 55 %), RV EF 26 % (norm > 50 %). After the contrast agent administration, a strip of late enhancement is visiable in the middle and external layer of the posterior and lateral wall of the left ventricle (Department of Radiology of the 2^nd Medical School and Motol Hospital, by Adla M.D.)

Video: see picture 13

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Table 3: Lake Louise Criteria, diagnosis of myocarditis in confirmed with 67 % sensitivity and 91 % specificity when at least 2 from 3 criteria are present [107].———————————————————————————————————————————————————————————————————————————-

LGE presence is described as an indicator of worse prognosis and increased mortality risk [27]. In a German-American study [27], patients with LGE presence had generally more distinctive left ventricular impairment and higher mortality than those without LGE presence (e. g. LV EF 37,5 % x 53,0 %),

However, negative CMRI result does not exclude the diagnosis of myocarditis because according to the references the examination does not have to provide sufficient sensitivity for the detection of myocarditis in the case of minor myocardial impairment [106]. The most frequently described disadvantage of the examination is its limited availability, time demands and primarily the fact that it is not able to distinguish specific types of myocarditis (GCM etc.), it does not provide information about aetiology of the inflammation and that the performance of LGE examination alone does not distinguish acute and chronic inflammation [106].

Author of the opening picture: Department of Radiology of the 2^nd Medical School and Motol Hospital, by Adla M.D.

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References:

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

27) GRÜN, S., SCHUMANN J. a et al. Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis: Predictors of Mortality and Incomplete Recovery. JACC. 2012, 59(18), 1604-1615.

97) KUCHYNKA P. Kapitola 8.1. Akutní myokarditida. In: MOŤOVSKÁ, Z. a et al. Novinky v akutní kardiologii. Praha: Mladá fronta, 2016. pp. 292–303. ISBN 978-80-204-3903

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

106) PLEVA, M. Kapitola 6: Akutní myokarditida. In: PLEVA, M. a P. OUŘEDNÍČEK. MRI srdce. Praha: Grada Publishing, 2012. pp. 83-86. ISBN 978-80-247-3931-1.

107) FRIEDRICH, M.G. a et al. Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper. Journal of the American College of Cardiology. 2009, 53(17), 1475-1487.

Příspěvek Cardiac magnetic resonance imaging (CMRI) pochází z Myokarditida

Chest X-Ray may visualize cardiomegaly and bigger pericardial effusion, pleural effusion or congestion in the pulmonary circulation [43, consultation with Adla, M.D.]. The finding may be even normal [43].

Author of the opening picture: Kalumet

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References:

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

104) FERRI, F. F. a et al. Ferri’s Clinical Advisor 2015: 5 Books in 1 [online]. -. USA: Elsevier, 2015 [cit. 2017-02-27]. pp. 807-809. ISBN 978-0-323-08375-1.

105) BACKER, D.D., ed. et al. Hemodynamic Monitoring Using Echocardiography in the Critically Ill [online]. -. Berlin: Springer, 2011 [cit. 2017-02-27]. pp. 124. ISBN 978-3-540-87954-1.

Příspěvek ECHO and Chest X-Ray pochází z Myokarditida

Picture 10: Diffuse ST elevation in a young male due to myocarditis / pericarditis (author of the picture and description: James Heilman, MD; https://commons.wikimedia.org/wiki/File:PericarditisMyocarditis.jpg?uselang=cs)

Author of the opening picture: Agateller – Anthony Atkielski

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References:

8) ZEMÁNEK D. Kapitola 15: Zánětlivé onemocnění myokardu. In: VESELKA, J. a V.ROHN. Kardiovaskulární medicína [online]. 1. vydání. Brno: Fasta Medica, 2015. ISBN 978-80-88056-00-3.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

97) KUCHYNKA P. Kapitola 8.1. Akutní myokarditida. In: MOŤOVSKÁ, Z. a et al. Novinky v akutní kardiologii. Praha: Mladá fronta, 2016. pp. 292–303. ISBN 978-80-204-3903

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

103) UKENA, CH. a et al. Prognostic electrocardiographic par ametersin patients with suspected myocarditis. European Journal of Heart Failure [online]. 2011, 13(-), 398-405 [cit. 2017-02-27].

Příspěvek ECG and Holter monitoring pochází z Myokarditida

Physical examination findings may be even normal or poor [8]. Besides the above-mentioned symptoms, even tachypnoea, tachycardia, worse tangible peripheral pulsation, thromboembolic symptoms, symptoms related to systematic disease (which are associated with myocarditis) may be found. During stethoscope examination, mitral valve murmur, pericardial or pleural murmur, pulmonary murmurs, and others may be present [43].

Author of the opening picture: Johannes Jansson

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References:

8) ZEMÁNEK D. Kapitola 15: Zánětlivé onemocnění myokardu. In: VESELKA, J. a V.ROHN. Kardiovaskulární medicína [online]. 1. vydání. Brno: Fasta Medica, 2015. ISBN 978-80-88056-00-3.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

101) TOMEK, V. Kapitola 56: Myokarditidy. In: CHALOUPECKÝ, V. a et al. Dětská kardiologie. Praha: Galén, 2006. pp. 327-329. ISBN 80-7262-406-5.

102) STARÁ, V. Nestrukturální srdeční onemocnění u dětí. Vox Pediatriae. 2006, 6(4), 26-32.

Příspěvek Subjective symptoms and physical examination pochází z Myokarditida

The disease may affect all age groups, even though its higher prevalence is in younger patients [19].

The latest diagnostical criteria are based on the statement of the European Society of Cardiology ([24], or table 2) when clinically suspect myocarditis is confirmed by the presence of at least one clinical and one diagnostic criterion, alternatively of two diagnostic criteria in asymptomatic patients, at the same time other possible causes of patients´ symptoms are excluded. Myocarditis and ICMP are definitely confirmed by an analysis of the myocardial samples from EMB. Its indication however abides by the recommendations of cardiological societies [43, 96].

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Table 2: Clinical and diagnostical criteria for suspected myocarditis by European Society of Cardiology when clinically suspected myocarditis is confirmed by the presence of at least one clinical and one diagnostic criterion, alternatively of two diagnostic criteria in asymptomatic patients and at the same time other possible causes of patients´ symptoms are excluded [24]————————————————————————————————————————————————————————————————————————————–

Author of the opening picture: Part of the web template

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References:

19) MÜLLEROVÁ J., NOVÁK M. a VÍTOVEC J. Myokarditidy. Kardiologická revue. 2003, -(2), 56-59.

24) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

97) KUCHYNKA P. Kapitola 8.1. Akutní myokarditida. In: MOŤOVSKÁ, Z. a et al. Novinky v akutní kardiologii. Praha: Mladá fronta, 2016. pp. 292–303. ISBN 978-80-204-3903-1.

98) KINDERMANN, I. a et al. Update on Myocarditis. Journal of the American College of Cardiology. 2012, 59(9), 779-792.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

100) KREJČÍ, J. Myokarditidy a zánětlivé kardiomyopatie. Kardiologická Revue Interní Medicína. 2015, 17(4), 288-294.

Příspěvek Diagnosis generally pochází z Myokarditida

The parasite is transferred by biting insect from Reduviidae family [26]. Afterward, it infects primarily muscle cells (of the myocardium, smooth and skeletal muscles) and ganglionic cells [92], damaged by the parasite´s activity.

The active phase of the disease comes 1 to 2 weeks after the exposure to the transmitter. The course is mostly asymptomatic or mild manifesting with fever, Romanov syndrome (one-sided oedema in eye socket area at the seat of attachment of a transmitter) and lymphadenopathy [93]. The symptoms disappear spontaneously in up to 90 % of patients [92, 93]. The mortality rate in this disease stage is 5 to 10 % as a result of myocarditis or meningoencephalitis [26, 94]. In 30 to 40 % of infected people, the disease progresses in chronic phase what may happen even decades after the contact with the transmitter [26, 92]. In the rest of the patients, the disease progresses in the latent phase with normal cardiological finding [92].

In chronic phase, impairment of the cardiovascular system is the most frequent, but even GIT and urogenital systems may be affected [94]. In case of chronic cardiovascular impairment, the disease progresses in so-called Chagas cardiomyopathy when references describe extensive changes in heart structure and function – myocardial fibrosis, the direct damage of the heart electrical system, ventricular dilatation, production of thrombus and aneurysms of the left ventricular apex [26, 92, 94]. The clinical picture of patients is very variable. Besides above-mentioned changes, there are described even ECG changes like ventricular arrhythmias, AV block of the 1^st degree, ventricular tachycardia, ST and PQ segment changes etc. [92, 93 ,94]. Bilateral heart failure with the predominance of the right-heart failure symptoms is an often complication and sudden cardiac death is also not an exception [92]. Therapy consists primarily of anti-parasitic treatment and therapy of heart failure (ACE inhibitors, beta blockers, diuretics, amiodaron, ICD etc.) and of thromboembolism, [92, 93]. Prognosis is variable and is based on the extent of cardiovascular damage, which is the main cause of mortality in infected patients [93, 95].

Author of the opening picture: Public domain

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References:

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

91) What is Chagas disease? WHO [online]. -: -, 2016 [cit. 2017-02-09].

92) JR., RASSI a et al. Chagas disease. Lancet. 2010, 375(-), 1388-1402.

93) H., MALIK a et al. The Epidemiology, Clinical Manifestations, and Management of Chagas Heart Disease. Clin. Cardiol. 2015, 38(9), 565-569.

94) BYSTRIANSKY. Kardiovaskulárne postihnutie pri Chagasovej chorobe. Očkování a cestovní medicína. 2015, 6(-), 35-38.

95) -X., LESCURE a et al. Chagas disease: changes in knowledge and management. Lancet Infect Dis. 2010, 10(-), 556-570.

Příspěvek Chagas disease pochází z Myokarditida

Systematic lupus erythematosus (SLE) is a multiorgan systematic disease affecting skin, lungs and cardiovascular and other systems. Cardiac manifestation is present in 50 % of patients and myocarditis specifically in approximately 10 % [75, 76]. Manifestation and symptoms are similar to other myocarditis types. Signs of heart failure may be observed. Similarly, resources describe even non-specific repolarization changes on ECG together with sinus tachycardia and the presence of segmental or global left ventricular hypokinesis, ventricular dilatation, pericardial effusion and decreased EF [75, 77]. According to the references, CMRI proves besides the above-mentioned findings even myocardial fibrosis. Opinions differ in the question of the benefit of EMB [75]. SLE myocarditis is mostly treated with standard heart failure therapy and with immunosuppressive therapy including corticosteroids [76, 77]. In a Chinese study of 25 patients, hospital mortality was 4 % [77].

Inflammatory intestinal diseases (ulcerative colitis and Crohn´s disease) are rarely complicated by myocarditis. Ulcerative colitis and Crohn´s disease are, in some cases, put in association with GCM (see chapter GCM). Their aetiology may include even mesalamine [78] and lack of selenium [79]. Manifestation, diagnosis algorithm, and the findings are similar to those in other types of myocarditis. They may present even under the picture of a cardiogenic shock [78]. No specific therapy is known. Heart failure therapy is administered if necessary, alternatively, in some cases, symptoms may improve after the discontinuing of mesalamine [78, 80].

Coeliac disease is a chronic inflammatory disease of the small intestine. Its sizeable prevalence was detected in both myocarditis (4,4 %,) [81] and idiopathic DCMP (5,7 %), [82]. Pathogenesis of myocarditis in patients with coeliac disease is unclear. Involvement of autoimmune mechanism is described what was proved even by results of an Italian study [81] when in all patients with myocarditis and coeliac disease cardiac auto-antibodies were detected. There are also speculations about the role of other antibodies which are produced in patients with coeliac disease and the changes of intestinal permeability and so influencing of levels of substances involved in the metabolism of cardiomyocytes could also play an important role [81, 83]. Manifestation is variable. Even the death of patients was described in some cases [84]. In the Italian study [81], 5 patients presented with heart failure resisted to standard pharmacotherapy and 4 with ventricular arrhythmias without syncope. In all patients, the gluten-free diet was applied and in patients with heart failure even immunosuppressive therapy because all patients had no infectious agent in the myocardium according to EMB. The therapy led to the improvement in the heart function and general state of health.

Rheumatic fever is a disease affecting different organs (joints, heart, central nervous system), arising on the autoimmune bases after untreated streptococcus infection [76, 88]. Its prevalence is often primarily in developing countries with the prevalence up to 100 cases per 100 000 inhabitants per year [88]. Cardiac impairment is present in up to 50 % of cases [76, 88] including impairment of valves, coronary arteries and carditis when the pericardium, myocardium (presence of Aschoff bodies, [38]) and endocardium are affected to varying degrees and which is also the most severe complication of rheumatic fever [88]. The prevalence of rheumatic heart disease was in 2015 almost 35 million cases [89]. Pathogenesis according to the resources lies primarily in the production of auto-antibodies against myosin and sarcolemma components [88]. The existence of rheumatic myocarditis was questioned several times already [90] because of the absence of well-marked troponin elevation and ECHO parameters changes, but the diagnosis was not completely rejected. Diagnosis of rheumatic myocarditis is thus highly challenging. Patients with rheumatic carditis may manifest even with heart failure or arrhythmias [88]. Therapy includes corticosteroids, salicylates, Penicillium, alternatively heart failure therapy [88]. The issue of rheumatic fever and carditis is far extensive. This chapter summarized only some pieces of knowledge.

Author of the opening picture: Lennart81

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References:

75) MASON J. C. Chapter 84: Rheumatic Diseases and the Cardiovascular System. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medicine. Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1843–1862. ISBN 978-1-4557-5133-4.

76) Srdce a systémová onemocnění. ECardio.cz [online]. -: -, – [cit. 2017-02-05].

77) ZHANG a et al. Lupus Myocarditis: A Case–Control Study from China. Chin Med J (Engl) [online]. 2015, 128(19), 2588-2594 [cit. 2017-02-05].

78) Recurrent lymphocytic myocarditis in a young male with ulcerative colitis. Varnavas, Varnavas C et al. “Recurrent Lymphocytic Myocarditis in a Young Male with Ulcerative Colitis.” European Journal of Medical Research 19.1 (2014): 11. PMC. Web. 5 Feb. 2017. [online]. 2014, 19(1), – [cit. 2017-02-05].

79) H., KATSANOS a et al. The heart in inflammatory bowel disease. ANNALS OF GASTROENTEROLOGY. 2002, 15(2), 124-133.

80) ROCZEK a et al. Myopericarditis in a patient with ulcerative colitis treated with mesalamine—Case report and review of the literature. Journal of Cardiology Cases [online]. 2014, 10(-), 104-107 [cit. 2017-02-05].

81) FRUSTACI a et al. Celiac Disease Associated With Autoimmune Myocarditis. Circulation [online]. 2002, 105(22), 2611-2618 [cit. 2017-02-05].

82) ZAHMATKESHAN a et al. Prevalence of coeliac disease in idiopathic dilated cardiomyopathy. Iran J Pediatr [online]. 2014, 24(5), 587-592 [cit. 2017-02-05].

83) ROMAGNOLI a et al. Association between celiac disease and idiopathic dilated cardiomyopathy: a case report. Internal and Emergency Medicine [online]. 2011, 6(2), 125-128 [cit. 2017-02-05].

84) BOSKOVIC a et al. Cardiomyopathy Associated with Celiac Disease in Childhood. Case Rep Gastrointest Med [online]. 2012, 2012(-), – [cit. 2017-02-05].

88) HROBOŇOVÁ V. Kapitola 58: Revmatická horečka In V., CHALOUPECKÝ a et al. Dětská kardiologie. Praha: Galén, 2006. pp. 335-339 ISBN 80-7262-406-5.

89) GLOBAL BURDEN OF DISEASE STUDY 2015. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. 2016, 388(-), 1546-1602, konkrétně 1563.

90) KAMBLOCK a et al. Does rheumatic myocarditis really exists? Systematic study with echocardiography and cardiac troponin I blood levels. European Heart Journal. 2003, 24(-), 855-862.

Příspěvek Myocarditis connected with autoimmune diseases pochází z Myokarditida

Aetiology of myocarditis in HIV positive patients is unclear. Besides a direct viral infection with HIV, myocarditis could be caused by different infections in association with immunosuppression of the immune system (Toxoplasma gondii, Mycobacterium tuberculosis, EBV, Coxsackie B, CMV etc.), [63, 64], autoimmune mechanisms (auto-antibodies production), [65], drug toxicity, nutritive conditions (for example lack of selenium), [66] and mitochondrial dysfunction as a result of viral activity [69]. Even higher levels of TNF alpha, IL-6, and other cytokines were observed in patients.

Manifestation and clinical picture of HIV positive patients with myocarditis are similar to other myocarditis types and also include a wide spectrum from asymptomatic individuals to cases presenting as a sudden death [70].

Treatment of myocarditis in HIV positive individuals is still not standardized including heart failure management, however, still standard heart failure therapy (ACE inhibitors, beta blocker, alternatively other therapeutic options) is recommended, [67, 68]. Some resources state that opportunist infection should be treated aggressively [34]. The role of antiretroviral therapy in the therapy of myocarditis in HIV positive individuals is uncertain. Rather its protective effect is described [66, 67]. Immunological therapy is also not standardized, even though in HIV positive children, therapy with IVIG was connected with the heart function improvement [71]. Controversial is treatment with mechanical supports and with heart transplant [67]. When nutritional deficit occurs, use of selenium, multivitamins and other substances is recommended [34].

Prognosis of patients is generally unclear and often unfavorable. There is a worse prognosis primarily in patients with the development of heart failure [34]. In a study including even 45 patients with HIV induced cardiomyopathy, this group belonged to groups with the worst prognosis and 5-year survival rate of 25 % [72]. Other study described the median of the survival in patients with AIDS and cardiomyopathy 101 days in comparison with 472 days in patients without cardiac manifestation [73]. In a study of HIV positive children, the better prognosis was described [74]. 5-year mortality based on the left ventricular FS score varied between 15 and 55 %.

Author of the opening picture: BruceBlaus

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References:

33) CAMBREA S. C. Chapter 8: Myocarditis in HIV Positive Patients. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 165-182. ISBN: 978-1-63242-083-1.

34) FISHER S. D., LIPSHULTZ S. E. Cardiovascular Abnormalities in HIV-Infected Individuals.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medicine. Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1624–1635. ISBN 978-1-4557-5133-4.

63) SHIRANI a et al. CARDIOVASCULAR IMAGING IN CLINICAL AND EXPERIMENTAL ACUTE INFECTIOUS MYOCARDITIS. Frontiers in Bioscience. 2003, 8(-), e323 – e336.

64) Cardiac Involvement in the Acquired Immunodeficiency Syndrome: A Multicenter Clinical-Pathological Study. Mary Ann Liebert, Inc. publishers [online]. USA: Mary Ann Liebert, Inc. publishers, 2009 [cit. 2017-02-05].

65) F., CURRIE a et al. Cardiac autoimmunity in HIV related heart muscle disease. Heart [online]. 1998, 79(-), 599-604 [cit. 2017-02-05].

66) H., LUMSDEN a et al. The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds. BioMed Research International [online]. 2016, 2016(-), 9 stránek [cit. 2017-02-05].

67) REMICK a et al. Heart Failure in Patients With Human Immunodeficiency Virus Infection. Circulation [online]. 2014, 129(17), 1781-1789 [cit. 2017-02-05].

68) OLSON L. J. Chapter 22: Myocarditis Associated With Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. In: L.T., JR., COOPER, ed. Myocarditis: From Bench to Bedside. USA: Humana Press, 2003. pp. 545–558. ISBN 1-58829-112-X.

69) S., BLOOMFIELD a et al. Human Immunodeficiency Virus and Heart Failure in Low-and Middle-Income Countries. JACC: Heart Failure. 2015, 3(8), 579–590.

70) KISELNIK a et al. Acute Myocarditis and Myopathy as Presenting Manifestations of Human Immunodeficiency Virus Infection. IMAJ [online]. 2015, 17(-), 524-525 [cit. 2017-02-05].

71) E., LIPSHULTZ a et al. Immunoglobulins and Left Ventricular Structure and Function in Pediatric HIV Infection. Circulation [online]. 1995, 92(8), 2220-2225 [cit. 2017-02-05].

72) M., FELKER a et al. Underlying Causes and Long-Term Survival in Patients with Initially Unexplained Cardiomyopathy. The New England Journal of Medicine [online]. 2000, 342(-), 1077-1084 [cit. 2017-02-05].

73) F., CURRIE a et al. Heart muscle disease related to HIV infection: prognostic implications. BMJ [online]. 1994, 309(1605), – [cit. 2017-02-05].

74) D., FISHER a et al. Mild dilated cardiomyopathy and increased left ventricular mass predict mortality: The Prospective P2C2 HIV Multicenter Study. America Heart Journal [online]. 2005, 150(3), 439–447 [cit. 2017-02-05].

Příspěvek Myocarditis in HIV positive patients pochází z Myokarditida

Clinical manifestation of cardiac sarcoidosis is varied. It presents with heart failure under the picture of dilated or restrictive cardiomyopathy and with arrhythmias [50]. In the Finnish study published in 2014 [60], 44 % of patients with cardiac sarcoidosis presented with AV block, 33 % with ventricular tachycardia or fibrillation and 18 % with heart failure. The same study evaluated even ECG, ECHO, CMRI and PET findings, treatment results and mortality. A very often ECG finding was AV block of the 2^nd or 3^rd degree (45 %), RBBB (37 %) and LBBB (21 %). During ECHO examinations, except decreased left ventricular EF in approximately 50 % of patients, even left ventricular dilatation and changes in the dimensions of the interventricular septum were described. There were even some findings of the right ventricular aneurysm [50].

CMRI has an important role in the diagnosis of cardiac sarcoidosis where except above-mentioned findings, even LGE is presented in the most of patients with the localization in basal segments of the interventricular septum and lateral wall of the LV in the epicardium and the middle layer of the myocardium [50]. PET examination is also used when inflammatory activity is detected by 18F-FDG (fluorodeoxyglucose), [50]. The sensitivity of EMB in cardiac sarcoidosis is 20 to 25 % [50]. The sensitivity was in one Canadian patient increased with the previous electroanatomic mapping of the heart ventricle [61].

Like in eosinophilic and giant-cell myocarditis, even in cardiac sarcoidosis, the main therapeutic method is immunosuppressive therapy. This treatment is usually administered in monotherapy or in combination with other immunosuppressive drugs, primarily methotrexate. In the treatment of arrhythmias and prevention of sudden cardiac death, implantation of a permanent pacemaker or ICD is considered [62]. ACE inhibitors, beta-blockers and alternatively diuretics are recommended in heart failure treatment. Digoxin is not commonly recommended [58]. Primarily in patients with advanced heart failure, the heart transplant is sometimes necessary [50]. Prognosis varies in different studies. According to the Finnish study [60], 10-year survival rate including patient without the necessity of heart transplant was 83 % (for comparison with the study from 2003 – 5-year survival rate was 70 %), [49]. Worse prognosis is in patients with an isolated form of cardiac sarcoidosis with an initial manifestation with heart failure with the 10-year survival rate of 52 %.

Author of the opening picture: Yale Rosen from USA

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References:

49) OKURA a et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. Journal of the American College of Cardiology [online]. 2003, 41(2), 322 [cit. 2017-02-05].

50) KUBÁNEK a VOSKA L. Obrovskobuněčná myokarditida a sarkoidóza srdce – update 2015. Kardiologická revue – Interní medicína. 17(4), 295-299.

58) T., JR., COOPER. Chapter 18: Cardiac Sarcoidosis. In: L.T., JR., COOPER, ed. Myocarditis: From Bench to Bedside. USA: Humana Press, 2003. pp. 421-436. ISBN 1-58829-112-X.

59) MORIMOTO a et al. Epidemiology of sarcoidosis in Japan. European Respiratory Journal [online]. 2008, 31(-), 372-379 [cit. 2017-02-07].

60) KANDOLIN. Cardiac Sarcoidosis: Epidemiology, Characteristics and Outcome over 25 Years in a Nationwide Study. Circulation [online]. 2014, 2014(-), 1-35 [cit. 2017-02-05].

61) B., NERY a et al. Isolated Cardiac Sarcoidosis: Establishing the Diagnosis With Electroanatomic Mapping-Guided Endomyocardial Biopsy. Canadian Journal of Cardiology. 2013, 2013(29), 1015.e1 – 1015.e3.

62) H., BIRNIE a et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis. Heart Rhythm. 2014, 11(7), 1304–1323.

Příspěvek Cardiac sarcoidosis pochází z Myokarditida

GCM is characterized by the histopathological finding of giant multinuclear cells, infiltration with eosinophils and T lymphocytes and necrosis of cardiomyocytes.

Giant cells are localized primarily at the edge of the myocardial necrosis [48]. In contrast to sarcoidosis, in GCM there are observed smaller fibrous changes and a minimal number of irregularly shaped granulomas [49, 50]. The presence of bordered granulomas confirms rather the diagnosis of sarcoidosis [51]. These changes do not have to in some cases affect just the ventricular myocardium, but also the myocardium of atriums [48]. GCM is definitively confirmed just with EMB.

GCM prevalence is very low. In the USA, the disease is even written in the list of rare disease [52]. In a retrospective study of patients who underwent EMB, GCM was confirmed just in 4 from 851 performed biopsies [53]. Specifically, in children, its prevalence is even lower. Up to the year 2006, there were just 14 documented cases [54] with the prevalence of females.

Pathogenesis of GCM in not still quite clear. Most likely, it arises on the basis of autoimmune disorder [50]. Up to 20 % of patients had a simultaneous presence of an autoimmune disease (for example Crohn´s disease, ulcerative colitis, autoimmune thyroiditis or myasthenia), [55, 56].

It is often a fatal disease presenting in fulminant form and even with a transition to the cardiogenic shock. In the research of GCM from 1997, 75 % of patients presented with heart failure, 14 % with ventricular tachycardia and 5 % with complete AV block [55]. Simultaneously, the effectiveness of immunosuppressants and corticosteroids therapy, which remain the main therapy of GCM up to the present, was researched. A prolongation of the median of the survival was described in patients with this therapy (12,3 months) in comparison with patients treated just with the heart failure therapy (3 months). The mortality rate of patients or the necessity of heart transplant was even up to 89 % [55]. Similar results were observed even in a study from 2003 with the 5-year survival rate of 22 % including patients without the necessity of the heart transplant [49].

In the Finnish study published in 2012, the 5-year survival rate was 52 % also including patients without the necessity of heart transplant [56].

The relapse of GCM was recorded in 20 to 25 % of patients after the heart transplant. It was mostly suppressed by higher doses of immunosuppressive drugs [54, 57].

Combined immunosuppressive therapy includes according to the resources usually the combination of corticosteroids with azathioprine or mycophenolate and cyclosporine. In the most of patients, ICD is indicated because of a high risk of death due to malignant arrhythmias [56, 57]. There are also many patients where the heart transplant is the only therapeutic option even though there are described some cases when patients were stabilized just with the immunosuppressive and heart failure therapy [57].

Author of the opening picture: Gregory Marcus, MD, MAS, FACC

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References:

48) J., DAVIES a et al. Idiopathic giant cell myocarditis-a distinctive clinico-pathological entity. British Heart Journal [online]. 1975, 1975(37), 192-195 [cit. 2017-02-05].

49) OKURA a et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. Journal of the American College of Cardiology [online]. 2003, 41(2), 322 [cit. 2017-02-05].

50) KUBÁNEK a VOSKA L. Obrovskobuněčná myokarditida a sarkoidóza srdce – update 2015. Kardiologická revue – Interní medicína. 17(4), 295-299.

51) T., JR., COOPER. Chapter 17: Idiopathic Giant Cell Myocarditis. In: L.T., JR., COOPER, ed. Myocarditis: From Bench to Bedside. USA: Humana Press, 2003. pp. 405-420. ISBN 1-58829-112-X.

52) Giant Cell Myocarditis. National Organization for Rare Disorders [online]. USA: -, 2006 [cit. 2017-02-07].

53) K., BENNETT a et al. Evaluation of the Role of Endomyocardial Biopsy in 851 Patients With Unexplained Heart Failure From 2000–2009. Circulation: Heart Failure [online]. 2013, 2013(6), 676-684 [cit. 2017-02-05].

54) D., BINHUTI a et al. Cardiac Transplantation for Pediatric Giant Cell Myocarditis. Journal of Heart Lung Transplant. 2006, 2006(25), 474-478.

55) T., JR., COOPER a et al. IDIOPATHIC GIANT-CELL MYOCARDITIS — NATURAL HISTORY AND TREATMENT. The New England Journal of Medicine. 1997, 1997(336), 1860-1866.

56) KANDOLIN a et al. Diagnosis, Treatment, and Outcome of Giant-Cell Myocarditis in the Era of Combined Immunosuppression. Circulation: Heart Failure [online]. 2013, 2013(6), 15-22 [cit. 2017-02-05].

57) A., CHAUDHRY a et al. Modern day management of giant cell myocarditis. International Journal of Cardiology. 2015, 2015(178), 82-84.

Příspěvek Giant-cell myocarditis pochází z Myokarditida

The basic characteristic of the disease in a finding of eosinophilia in blood. Its severity is assessed by the absolute number of eosinophils per mm³. Aetiology of eosinophilic myocarditis includes various agents – antibiotics (penicillin, sulfonamides, cephalosporine etc.), antipsychotics (clozapine), non-steroidal anti-inflammatory drugs (indomethacin), diuretics, some ACE-inhibitors (captopril and enalapril), digoxin, dobutamine, small-pox vaccine and others. Non-pharmacological causes of the eosinophilic heart impairment are parasitic infections, some systematic disorders (primarily Churg Strauss syndrome) and hematological diseases, various malignant diseases and idiopathic hypereosinophilic syndromes [44, 45].

Clinical manifestation and laboratory and imaging methods results are varied and may even detect no pathologies. In most of the patients, peripheral eosinophilia is present, however, its presence is not necessary for the diagnosis. The definitive diagnosis is confirmed by EMB findings [46]. A curiosity of LGE during CMRI examination in eosinophilic myocarditis is its localization in the subendocardial layer. In contrast to ischemic heart disease, the myocardial damage is not limited just in the areas supplied by coronary arteries [47].

Some authors set aside, in addition, acute eosinophilic necrotizing myocarditis accompanied by a distinct eosinophilia, necrosis and oedema of the myocardium and manifesting as fulminant myocarditis [25].

The most important therapeutic measure in patients with eosinophilic myocarditis is the removal of the agent if it is known. In most of the patients with non-infectious type of this myocarditis, immunosuppressive therapy consisting primarily from corticosteroids is indicated [46].

Author of the opening picture: Blausen Medical

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References:

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

25) ABDULLAH, M.A.A., L.P. STRAATMAN a et al. Eosinophilic myocarditis: Case series and review of literature. Canadian Journal of Cardiology. 2006, 22(14), 1233–1237.

44) BAANDRUP. Eosinophilic myocarditis. Herz. 2012, 2012(37), 849-853.

45) E., ECKART a et al. Incidence and Follow-Up of Inflammatory Cardiac Complications After Smallpox Vaccination. Journal of the American College of Cardiology. 2004, 44(1), 201-205.

46) KUCHYNKA a et al. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis. BioMed Research International [online]. 2016, 2016(-), 6 stran [cit. 2017-02-05].

47) E., PETERSEN a et al. Subendocardial and papillary muscle involvement in a patient with Churg-Strauss syndrome, detected by contrast enhanced cardiovascular magnetic resonance. Heart [online]. 2005, 91(1), e9 [cit. 2017-02-07].

Příspěvek Eosinophilic myocarditis pochází z Myokarditida

It is an uncommon form of myocarditis which is characterized by a fast progression of the disease. Usually in the term of just several days, often one or two, before the first manifestation of the disease, prodrome of a viral infection is quite frequent (fever, myalgia, arthralgia etc.). Patients present with acute heart failure and sometimes even with cardiogenic shock and a rapid decrease of the left ventricular ejection fraction may be observed [16]. Frequent ECHO finding is non-enlarged left ventricle with thickening of its walls [16]. In fulminant myocarditis, it is recommended to exclude giant cell and eosinophilic myocarditis as the cause of the disease, because they require specific therapy (see other chapters). If patients do not respond to the pharmacological treatment and/or their state of health deteriorates rapidly, mechanical cardiac support, including ECMO, is often necessary what then serves either as “bridge to recovery” or “bridge to transplant” [96]. When patients survive the acute stage of heart failure, their prognosis is usually favorable [16, 87]. According to the research from 2000 including 147 patients with myocarditis (14 of them with the fulminant form of myocarditis), the long-term prognosis of patients with fulminant myocarditis is even better than in patients with “classical” acute form. After 11 years, 93 % of patients with fulminant myocarditis (including patients without heart transplant) survived, compared to the group of patients with acute myocarditis with the survival rate of 45 % [87].

Acute myocarditis

Acute myocarditis is a “classical” form of myocarditis which differs from fulminant myocarditis in the milder initial course of the disease and often in the slower manifestation of symptoms. Symptoms of a viral infection (primarily of the respiratory and gastrointestinal system) may be observed in patients even several weeks before the cardiac manifestation. The myocarditis itself usually manifests according to the resources with heart failure, arrhythmias or chest pain mimicking acute coronary syndrome [16, 86].

Chronic myocarditis

It is a long-term damage to the myocardium with inflammatory processes. In the case that this process is connected with the systolic dysfunction and dilatation of the left ventricle, it is called ICMP. Earlier, chronic myocarditis was classified in chronic active form (repeated relapses of acute myocarditis connected with chronic inflammatory changes of the myocardium and with the fibrosis and left ventricular dysfunction) and chronic persisting form (presence of the persisting inflammatory infiltrate and necrosis of cardiomyocytes, however, without signs of the left ventricular dysfunction), [4, 43].

Authors of the opening picture: Video file from Bogabathina H, Olson P, Rathi V, Biederman R (2012). “Cardiac Sarcoidosis or Giant Cell Myocarditis? On Treatment Improvement of Fulminant Myocarditis as Demonstrated by Cardiovascular Magnetic Resonance Imaging”. Case Reports in Cardiology. DOI:10.1155/2012/647041. PMID 24826266. PMC: 4008442.

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References:

4) AL-AQEEDI R.F., Chapter 2: Clinical Presentation. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 33–69. ISBN: 978-1-63242-083-1.

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

43) M, HOLICKÁ a ŠPINAR J. Myokarditidy. ACTA MEDICINAE. 2013, 2013(7), 68-74.

86) E., AMM a COOPER L.T., JR. Management of myocarditis. Heart Metab. 2014, 62(2014), 8-12.

87) E., MCCARTHY a et al. Long-Term Outcome of Fulminant Myocarditis as Compared with Acute (Nonfulminant) Myocarditis. The New England Journal of Medicine [online]. 2000, 342(-), 690-695 [cit. 2017-02-07].

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

Příspěvek Fulminant, acute and chronic myocarditis pochází z Myokarditida

It may be classified based on the aetiology (infectious or non-infectious), further according to the histopathological finding (eosinophilic, lymphocytic, granulomatous, giant-cell), based on the clinical picture and manifestation (for example myocarditis connected with heart failure, arrhythmias etc.), [16, 22, 38]. The most commonly used classification is so-called clinical-pathological evaluation combining histopathological findings with the clinical course of the disease. According to the duration, myocarditis is usually classified in acute and chronic form, however, some authors replaced term chronic myocarditis with the term ICMP [8].

Perimyocarditis is a term used for myocarditis connected with the inflammation of the pericardium.

ICMP itself does not have any specific classification. It is mostly classified on the grounds of the EMB results, thus according to the presence or absence of the agent and inflammation [23, 29].

In the following chapters, there are mentioned “basic” and even rare or in other ways “unique” forms of myocarditis (eosinophilic and giant-cell myocarditis, myocarditis in HIV positive patients etc.). Due to the clear arrangement of the chapters about rare forms of myocarditis, these chapters contain even a brief description of the pathogenesis, if it is known, further the description of the clinical course, diagnostical and therapeutic methods and prognostic data. The aim of these chapters is to point at the heterogeneity of myocarditis.

Author of the opening picture: KGH

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References:

8) ZEMÁNEK D. Kapitola 15: Zánětlivé onemocnění myokardu. In: VESELKA, J. a V.ROHN. Kardiovaskulární medicína [online]. 1. vydání. Brno: Fasta Medica, 2015. ISBN 978-80-88056-00-3.

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

22) SAGAR, Sandeep, Peter P. LIU a Leslie T. COOPER, JR. Myocarditis. Lancet. 2012,379(-), 738–747.

23) SCHULTHEISS, Heinz-Peter, Uwe KÜHL a Leslie T. COOPER, JR. The management of myocarditis. European Heart Journal. 2011, 32(-), 2616–2625.

29 KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

38) ŠTEINER, I. Kardiopatologie: pro patology i kardiology. Praha: Galén, 2010. ISBN 978-80-7262-672-4.

Příspěvek Classification of myocarditis and ICMP pochází z Myokarditida

The histological finding may be very various. The most common one is lymphocytic infiltrate occurring in myocarditis with viral and toxic aetiology, further in Borellia burgdorferi infection, vasculitis, and other systematic disorders [16, 38]. In bacterial myocarditis, infiltrate contains neutrophils. Eosinophilic infiltrate is characteristic for eosinophilic myocarditis, some systematic disorders (like Churg Strauss syndrome) and parasitic aetiology of myocarditis. Aschoff bodies may be observed in rheumatic fever connected with myocarditis [38]. In the case of the cardiac sarcoidosis, granulomatous infiltrate is detected [16, 38].

According to older Dallas criteria, histopathological finding in patients with myocarditis was classified in active/borderline and non-confirmed myocarditis [3]. Active myocarditis was characterized by “a distinct leukocytic infiltrate accompanied by necrosis or cardiomyocytes degeneration” and borderline myocarditis was defined by “less expressed leukocytic infiltrate.” Dallas criteria have however their imperfections [42]. It is primarily the variability in the interpretation of the results of histopathological examination of the myocardium which are influenced by the experience of the evaluating expert and by the shortage of other accompanying immunohistochemical, PCR and else examinations [42]. According to these criteria, the agent of the inflammation and its presence cannot be detected what can be important in some patients in the question of a specific, primarily immunosuppressive, therapy. Because of this reason, the use of Dallas criteria alone is not recommended and on the grounds on experts´ consensus, it is necessary to use even other methods for the evaluation of the myocardium (see chapter Endomyocardial biopsy), [42].

Authors of the opening pictures: Kurt Deb, Behrus Djavidani, Stefan Buchner, Florian Poschenrieder, Norbert Heinicke, Stefan Feuerbach, Günter Riegger and Andreas Luchner; Ed Uthman, MD; dr n. med. Krystyna Bielnik, lek. med. Dariusz Młoczkowski, dr n. med. Tadeusz Modrzewski, lek. med. Dorota Snopkowska, prof. dr hab. med. Krzysztof W. Zieliński

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References:

3) T., ARETZ a et al. Myocarditis. A histopathologic definition and classification. The American Journal of Cardiovascular Pathology [online]. 1986, 1(1), 3-14 [cit. 2017-02-06].

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

38) ŠTEINER, I. Kardiopatologie: pro patology i kardiology. Praha: Galén, 2010. ISBN 978-80-7262-672-4.

42) L., BAUGHMAN. Diagnostika myokarditidy: Dallaským kritériím odzvonilo. Circulation-CZ. 2006, 5(1), 7-9.

Příspěvek Histopathology pochází z Myokarditida

Generally, pathogenesis of myocarditis is classified into three successive phases: acute phase (viremia), subacute phase and chronic (sometimes called myopathic) phase.

It is presumed that a number of aspects contribute to the development of myocarditis and/or ICMP like genetic predisposition supported by the fact that in some individuals whose encountered with an infectious agent causing myocarditis, the disease did not develop [85].

Acute phase (viremia)

This phase lasts for approximately first three days of the disease and it is characterized by the development of the viral infection and internalization of the virus into cardiomyocytes. In enteroviral and adenoviral myocarditis model, viruses use for their entrance into cells CAR (Coxsackie-adenovirus receptor) receptor. Adenovirus uses for its internalization even co-receptors, specifically integrins. On the other hand, enteroviruses use co-receptor DAF (Decay Accelerating Factor), called also as CD55 [36]. Receptor ICAM-1 is also related to the connection with the internalization of Coxsackie viruses into cardiomyocytes. Together with CAR, it belongs to the group of immunoglobulins. The results of the analysis of the expression of CAR receptors in patients with DCMP confirmed increased expression of these receptors whereas in other patients with severe heart failure these results were not observed. The increased expression could be genetically predisposed [36].

However, it is not a rule, that a viral agent attacks the cardiomyocytes directly. For example, in the case of PVB19, endothelial cells of the blood vessels are affected and the damage of the myocardium is mediated indirectly [23].

The viral internalization is followed by the damage of inner structures of cardiomyocytes. In enteroviral myocarditis, damage of dystrophin was observed what lead to the interruption of the dystrophin-glycoprotein complex what resulted in the disruption of the cytoskeleton and decay of the cell structure [26].

In the phase of viremia, cardiomyocytes are damaged by the direct toxic viral activity and its lytic activity. At the same time, this activity causes the exposure of the inner cell structures, primarily cardiac myosin antigens [26].

Via Toll-like receptors (TLR), inner cell signal pathways are activated including besides other things the activation of nuclear transcription factors what leads in the production of cytokines (primarily of interferons, interleukins and TNF factor) and also in the activation of the immune system [26, 37]. The leading role have primarily TLR-3 and 4 which are widened in the cardiovascular system bountifully [22, 26].

Subacute phase

Subacute phase is characterized by the immune response caused by the viral internalization into cardiomyocytes. It is in motion approximately between the 4^th and 14^th day of the disease. The immune response goal is the elimination of the viral agent. This phase is important even from the point of view of the further course of myocarditis. In the case of an excessive immune response, viral persistence even after the immune response, development of the autoimmune reaction or their combination, structural and functional damage of the myocardium may develop what could lead to the development of DCMP, or rather ICMP and chronic heart failure [22, 86].

Innate immunity reaction is characterized by the immune response activation and the production of cytokines and interleukins (in the initial phase especially of IL 1beta and TNF alpha), [26, 29] decreasing the viral replication [26].

It is followed by the humoral and cellular immune response. NK-cells activated by IL-2 infiltrates the myocardium and eliminates cardiomyocytes attacked by the virus [29].

The inflammatory response includes both cellular and later as a result of T cells activation even humoral part of the immune system when B cells activate and start the production of specific antibodies [24]. From the cellular immunity, macrophages, B lymphocytes, CD4 and CD8 T lymphocytes are involved in the inflammatory reaction [26]. CD4 T lymphocytes differentiate in several cellular subtypes like Th1 and TH2 and T regulating cells (Treg) which have together with other factors an important role in the suppression of the immune response [26].

In this phase, the production of anti-myosin and other autoantibodies may occur what happens as a result of the destruction of cardiomyocytes and the exposure of their inner structures on the principle of the molecular mimicry of the infectious agent and components of the host cell [26].

Chronic (myopathic) phase

This phase begins approximately with the 15^th day and ends 90^th day from the beginning of the disease (it could sometimes last even distinctively longer) and is highly important for the future disease course. After the elimination of the virus, suppression of the immune reaction should begin and myocarditis should heal up without any severe consequences for the patients what occur in 50 to 70 % of cases [96]. In the remaining part of patients, the disease may lead either to death or the heart transplant or the disease progresses in chronicity.

There are a lot of factors influencing the structure and function of the heart, primarily of the left heart ventricle. One of them is the extent of the myocardial damage because damaged and necrotic myocardial tissue is replaced by fibrous tissue which is not able to fulfill highly specialized functions of the myocardium. These changes are accompanied by the left ventricular remodelation which gradually reach the stage of the DCMP [22, 26]. Fibrous changes and remodelation are initiated already in the subacute phase of the disease by the activity of pro-fibrous cytokines, especially of TNF alpha, IL 1beta, IL 4, IL 17 and TGF beta 1 [41]. This damage is not caused just by the lytic activity of an infectious agent, but also by the elimination of cardiomyocytes attacked by the agent by the immune system, which in some cases may cause even more extensive damage of the tissue than the agent itself, however, at the cost of stopping the infection. There are of course even other aspects that have a share in the development of the DCMP on the grounds of a suffered myocarditis like if the elimination of the infectious agent was successful or not what may lead to other lytic activity of the agent or long-term immune system stimulation.

Last but not least, immune system activity has a crucial influence on a patient´s state of health. Continuing myocardial inflammation leads to further damage to cardiomyocytes and it may initiate even the production of autoantibodies against the inner cellular components of cardiomyocytes as mentioned in the previous paragraph. Most frequently autoantibodies are created against myosin, sarcolemma components, beta-adrenergic receptors, muscarine receptors, tropomyosin etc. [39]. Antibodies against some of the previously mentioned components were detected in serum in up to 59 % of patients with myocarditis. Moreover, even other changes may be observed like for example cardiomyocytes hypertrophy, increase of the extracellular space connected with the fibrous replacement and other changes which are described even in the left ventricular remodelation connected with the heart failure like for example changes of the ATP metabolism in the myocardium etc. [26, 40].

Author of the opening picture: BruceBlaus

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References:

22) SAGAR, Sandeep, Peter P. LIU a Leslie T. COOPER, JR. Myocarditis. Lancet. 2012,379(-), 738–747.

23) SCHULTHEISS, Heinz-Peter, Uwe KÜHL a Leslie T. COOPER, JR. The management of myocarditis. European Heart Journal. 2011, 32(-), 2616–2625.

26) COOPER L. T., JR., KNOWLTON K. U. Chapter 67: Myocarditis. In.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medic Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1589–1602. ISBN 978-1-4557-5133-4.

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

36) POLLER, W., H. FECHNER a et al. The molecular basis of cardiotropic viral infections. European Heart Journal Supplements [online]. 2002, -(4), 118–130 [cit. 2016-09-14].

37) LAURENT A. Chapter 3: Viral Myocarditis: Physiopathology and Diagnosis. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 69-86. ISBN: 978-1-63242-083-1.

39) CAFORIO, A.L.P, PANKUWEIT S., ARBUSTINI E., et al. Current state knowledge on aetiology, diagnosis, management, and Therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Disease. European Heart Journal. 2013, 34(-), 2636–2648 podle referencí 72, 77, 57, 64, 9, 50, 35, 36, 118, 52, 48, 55, 61–63, 66, 72, 74–76, 78, 84, 109, 88, 90, 92, 93, 98, 53, 62, 69, 89, 47, 48, 54, 58, 59, 70, 74–75, 88, 94, 98, 67 uvedených v tomto článku.

40) HASENFUSS, G., MANN, D. L. Chapter 22: Pathophysiology of Heart Failure. In.: D. P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medicine. Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 454–472. ISBN 978-1-4557-5133-4.

41) ELAMM, Chantal, DeLisa FAIRWEATHER a Leslie T. COOPER. Pathogenesis and diagnosis of myocarditis. Heart. 2012, -(-), – podle referencí 11, 20, 30, 32 uvedených v tomto článku.

85) DENNERT a et al. Acute viral myocarditis. European Heart Journal. 2008, 29(-), 2073-2082.

86) E., AMM a COOPER L.T., JR. Management of myocarditis. Heart Metab. 2014, 62(2014), 8-12.

96) Onemocnění myokardu: Myokarditida, zánětlivá kardiomyopatie. ECardio.cz [online]. -: -, – [cit. 2017-01-30].

Příspěvek Pathogenesis pochází z Myokarditida

The most frequent cause of myocarditis and ICMP are considered infectious agents, whereas groups of viruses which are predominant in the aetiology of myocarditis and ICMP are changing depending of time and geographical location. For a long period of time, dominant agents of these conditions in Europe and North America were considered enteroviruses and adenoviruses. In present, they have been replaced by herpes viruses and parvovirus B19 (PVB19) [170]. The most frequent viral agents of myocarditis and ICMP generally are considered PVB19, human herpes virus 6, cytomegalovirus and Epstein-Barr virus [170]. However, results of the studies differ in the question of the extent of the representation of these viruses in aetiology of myocarditis and ICMP. In study published in 2012, including 203 with myocarditis who underwent EMB, genome of PVB19 was detected in 55,7 % of individuals, HHV-6 in 24,1 % and dual infection of PVB19 and HHV-6 in 17,2 % [27].

In a Czech study including 50 patients with DCMP who underwent EMB, viral genome was detected in 29 individuals, and 27 of these individuals (93 %) constituted PVB19 [28].

However, the importance of PVB19 in aetiology of myocarditis was repeatedly called into question because the genome of PVB19 was detected even in patients without no signs of myocarditis and ICMP [35].

Nevertheless, enteroviruses (primarily Coxsackie), adenoviruses, hepatitis C virus and influenza virus still remain relatively important viral agents of myocarditis and ICMP. In Japan, even cases of H1N1 virus myocarditis were described [20].

Bacteria are also no less important agents of myocarditis and ICMP. In the Czech Republic, myocarditis caused by Borellia burgdorferi has relatively often incidence [29]. In the developing countries, the disease may be caused even by meningococcus and diphteriae [22]. Primarily in the area of the Central and South America, infection of Trypanosoma cruzi dominates developing often in so called Chagas disease [26].

Nonnegligible parts of aetiology of myocarditis are also different cardiotoxic drugs, ethanol and addictive drugs (chemotherapeutics, cocaine), hypersensitive allergic reactions (e.g. by ATB or antidepressants) and systematic inflammatory disorders (primarily connective tissue diseases). As for the hypersensitive reactions caused by antidepressant, myocarditis was described as a complication for example in the therapy with clozapine. In Australian study from 1993 to 2003 including 116 patients treating with clozapine, its incidence varied between 0,7 to 1,2 %, including 10,3 % fatal cases of myocarditis [31].

Myocarditis remains a frequent complication in patients with HIV infection, especially in patients with AIDS when myocarditis is confirmed post-mortem in up to 52 % of individuals [32]. In up to 25 % of patients, HIV infection is connected with DCMP [34]. Pathogenesis of myocarditis in HIV positive patients remains still unclear. It may include a direct effect of the HIV virus on the myocardium or the development of myocarditis in these patients may be connected with the weakened immune system and myocarditis could be thus caused by a different agent, for example toxoplasmosis [33].

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Table 1: Aetiology of myocarditis (based on references – 4, 8–18), bold the most common agents of myocarditis based on references 4, 8-18

Author of the opening picture: Thomas Splettstoesser

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References:

4) AL-AQEEDI R.F., Chapter 2: Clinical Presentation. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 33–69. ISBN: 978-1-63242-083-1.

8) ZEMÁNEK D. Kapitola 15: Zánětlivé onemocnění myokardu. In: VESELKA, J. a V.ROHN. Kardiovaskulární medicína [online]. 1. vydání. Brno: Fasta Medica, 2015. ISBN 978-80-88056-00-3.

9) BASSO, C. a F. CALABRESE. Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovascular Research [online]. 2001, -(50), 290-300 [cit. 2016-09-02].

10) TOWBIN, J. A., A. P. LOWE a et al. Incidence, Causes, and Outcomes of Dilated Cardiomyopathy in Children. JAMA. 2006, -(296), 1867-1876.

11) O´CONNELL, J. B., A. HERSKOWITZ a et al. A Clinical Trial of Immunosuppressive Therapy for Myocarditis. New England Journal of Medicine. 1995, -(333), 269-275.

12) CANTER, CH. E., M. W. CUNNINGHAMB a L. T. COOPER. Recent clinical and translational research on pediatric myocarditis. Prog Pediatr Cardiol. 2011, 32(1), 15–18.

13) UHL, T. L. Viral Myocarditis in Children. PediatricCare. 2008, 28(1), 42–63. (podle Friedman RA. Myocarditis. In: Garson A, Bricher JT, McNamara DG, eds. The Science and Practice of Pediatric Cardiology. Philadelphia, PA: Lea & Febiger; 1990: 1577-1589. + Park MK, Troxler RG. Pediatric Cardiology for Practitioners. 4th ed. St Louis, MO: Mosby; 2002:289-290.)

14) FABRE, A. a M. N. SHEPPARD. Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart. 2006, -(92), 316-320.

15) FAQ on Sudden Death and Myocarditis. Myocarditis Foundation [online]. -: -, 2012 [cit. 2016-10-18]. (Podle Feldman AM, McNamara D. Myocarditis. The New England journal of medicine 2000;343:1388-98.)

16) KUBÁNEK M., Kapitola 8.2.: Myokarditidy. In: KAUTZNER J., MELENOVSKÝ V., et al. Srdeční selhání – aktuality pro klinickou praxi. Praha: Mladá fronta a.s., 2015. pp. 147–157. ISBN: 978-80-204-3573-6.

17) TAVLI V., GUVEN B., Chapter 1: Myocarditis in Childhood: An Update on Etiology, Diagnosis and Management. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 3–32. ISBN: 978-1-63242-083-1.

18) OMAR H.R., ABDELMALAK H., HELAL E., MIKHAEIL Y., FATHY A. Chapter 5: Perimyocarditis. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 105–118. ISBN: 978-1-63242-083-1.

20) UKIMURA a et al. A National Survey on Myocarditis Associated With the 2009 Influenza A (H1N1) Pandemic in Japan. Circulation Journal. 2010, 74(-), 2193-2199.

22) SAGAR, Sandeep, Peter P. LIU a Leslie T. COOPER, JR. Myocarditis. Lancet. 2012,379(-), 738–747.

27) GRÜN, S., SCHUMANN J. a et al. Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis: Predictors of Mortality and Incomplete Recovery. JACC. 2012, 59(18), 1604-1615.

28) KREJČÍ, J., P. HUDE a et al. Endomyokardiální biopsie u recentní dilatační kardiomyopatie – zhodnocení vstupních charakteristik prvních padesáti nemocných. Cor et Vasa. 2011, -(53), 623-629.

29) KUCHYNKA, P. Nové diagnostické a terapeutické aspekty zánětlivé kardiomyopatie. Praha, 2011. Disertační práce. 1. LF UK.

31) HAAS, S. J., R. HILL a et al. Clozapine-Associated Myocarditis: Review of 116 Cases of Suspected Myocarditis Associated with the Use of Clozapine in Australia During 1993–2003. Drug Safety. 2007, 30(1), 47-57.

32) ANDERSON, D. W., R. VIRMANI a et al. Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome. Jornal of American College of Cardiology. 1988, 11(4), 792-799.

33) CAMBREA S. C. Chapter 8: Myocarditis in HIV Positive Patients. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 165-182. ISBN: 978-1-63242-083-1.

34) FISHER S. D., LIPSHULTZ S. E. Cardiovascular Abnormalities in HIV-Infected Individuals.: D.P., ZIPES, MANN D.L., LIBBY P., BONOW R.O. a BRAUNWALD E. (eds.). Braunwald´s Heart Disease: A Textbook of Cardiovascular medicine. Tenth edition. Philadelphia: Elsevier Saunders, 2015. pp. 1624–1635. ISBN 978-1-4557-5133-4.

35) KUETHE, F., J. LINDNER a et al. Prevalence of Parvovirus B19 and Human Bocavirus DNA in the Heart of Patients with no Evidence of Dilated Cardiomyopathy or Myocarditis. Clinical Infectious Diseases. 2009, -(49), 1660-1666.

170) SCHULTZ, J.C. a et al. Diagnosis and Treatment of Viral Myocarditis. Mayo Clin Proc [online]. 2009, 84(11), 1001-1009 [cit. 2017-03-01].

Příspěvek Aetiology pochází z Myokarditida

Epidemiological studies are thus facing a number of limitations. A certain proof of myocarditis or ICMP is gained primarily with the endomyocardial biopsy (EMB). However, the evaluation of EMB samples was in some researches performed just on the grounds of the Dallas criteria which are not sufficient enough for the diagnosis of myocarditis according to some references [42, 140]. The main limitation is considered primarily a low test sensitivity and relatively high demands for the experiences of an expert evaluating the results.

Based on the Finnish epidemiological study from 1970´s and 1980´s, incidence of myocarditis was 0,17 cases per 1000 inhabitants per year [6]. The post-mortem EMB incidence of myocarditis in a Swedish study from Malmö was 1,06 % [7].

In Myocarditis Treatment Trial study, myocarditis was diagnosed on the grounds of the histopathological criteria in 10 % of performed EMBs [11]. It also concluded information about mortality of patients with myocarditis and the necessity of heart transplant. Study included 111 patients, 34 of them died and 10 underwent heart transplant. The mortality in the 4^th year of the study was even more than 50 %. Other resources report about a high mortality and necessity of heart transplant primarily in paediatric patients where the average mortality and heart transplant necessity is around 30 % [12]. At the same time, this number increases in infants, reaching in the case of new-borns up to 75% mortality rate [13]. In the present, the incidence of myocarditis in Europe is considered approximately 131 cases per 1 million inhabitants per year [8].

Based on Global Burden of Disease study, over 2,5 million cases of myocarditis and cardiomyopathies was reported worldwide in 2015 including 156 thousand cases of acute myocarditis. Moreover, both groups reported over 20% increase of cases when comparing with 2005 [89].

Myocarditis is considered as a cause of sudden cardiac death, primarily in young individuals, in 9 to 20 % [14,15], based on bioptically taken samples of the myocardium. However, some studies have found signs of myocarditis bioptically in up to 42 % of cases [9].

Myocarditis very significantly contributes to the development of the dilated cardiomyopathy (DCMP). It is stated that its part in the development of the DCMP is around 20 %, however an American study which pursued the identification of causes of the DCMP in children, confirmed the diagnosis of myocarditis in 46 % of cases [10].

The representation of myocarditis in the development of heart failure varies from 0,5 to 4 % [30].

The results of these and other studies thus make myocarditis the most frequent aetiology of the DCMP and so it is ICMP [99].

Author of the opening picture: vlastní zdroj

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References:

6) KARJALAINEN, J. a J. HEIKKILÄ. Incidence of three presentations of acute myocarditis in young men in military service: A 20-year experience. European Heart Journal. 1999, -(20), 1120-1125.

7) GRAVANIS, M.B. a N.H. STERNBY. Incidence of myocarditis. A 10-year autopsy study from Malmö, Sweden. Arch Pathol Lab Med [online]. 1991, 115(4), 390-392 [cit. 2016-09-02].

9) BASSO, C. a F. CALABRESE. Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings. Cardiovascular Research [online]. 2001, -(50), 290-300 [cit. 2016-09-02].

10) TOWBIN, J. A., A. P. LOWE a et al. Incidence, Causes, and Outcomes of Dilated Cardiomyopathy in Children. JAMA. 2006, -(296), 1867-1876.

11) O´CONNELL, J. B., A. HERSKOWITZ a et al. A Clinical Trial of Immunosuppressive Therapy for Myocarditis. New England Journal of Medicine. 1995, -(333), 269-275.

12) CANTER, CH. E., M. W. CUNNINGHAMB a L. T. COOPER. Recent clinical and translational research on pediatric myocarditis. Prog Pediatr Cardiol. 2011, 32(1), 15–18.

13) UHL, T. L. Viral Myocarditis in Children. PediatricCare. 2008, 28(1), 42–63. (podle Friedman RA. Myocarditis. In: Garson A, Bricher JT, McNamara DG, eds. The Science and Practice of Pediatric Cardiology. Philadelphia, PA: Lea & Febiger; 1990: 1577-1589. + Park MK, Troxler RG. Pediatric Cardiology for Practitioners. 4th ed. St Louis, MO: Mosby; 2002:289-290.)

14) FABRE, A. a M. N. SHEPPARD. Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart. 2006, -(92), 316-320.

15) FAQ on Sudden Death and Myocarditis. Myocarditis Foundation [online]. -: -, 2012 [cit. 2016-10-18]. (Podle Feldman AM, McNamara D. Myocarditis. The New England journal of medicine 2000;343:1388-98.)

30) COOPER JR., L.T., A. KEREN a et al. The Global Burden of Myocarditis: Part 1: A Systematic Literature Review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. Global Heart. 2014, 9(1), 121-129.

42) L., BAUGHMAN. Diagnostika myokarditidy: Dallaským kritériím odzvonilo. Circulation-CZ. 2006, 5(1), 7-9.

89) GLOBAL BURDEN OF DISEASE STUDY 2015. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. 2016, 388(-), 1546-1602, konkrétně 1563.

99) KUCHYNKA, P. a et al. Myokarditida a zánětlivá kardiomyopatie. Kapitoly z kardiologie. 2013, 3(-), 87-91.

140) PALEČEK, T. Inflammatory cardiomyopathy: Still many questions await answers. Cor et Vasa. 2013, 55(-), E341-E344.

Příspěvek Epidemiology pochází z Myokarditida

According to the WHO 1995 definition, ICMP is defined as “myocarditis connected with the cardiac dysfunction [1],” and at the same time myocarditis is defined as “an inflammatory disease of the myocardium diagnosed by established histological, immunological and immunohistochemical methods.”

In 2008, ICMP was classified in the classification of cardiomyopathies of the European Society of Cardiology to dilated cardiomyopathies and it is defined by “the presence of chronic inflammatory cells in the myocardium in association with the left ventricular dilatation and reduced ejection fraction.” Dilated cardiomyopathy is according to the same classification defined by “the presence of the left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment.” [2]

According to histological criteria, specifically according to Dallas criteria, the diagnosis of myocarditis is confirmed by “the presence of the inflammatory infiltrate of the myocardium with the degeneration or necrosis of cardiomyocytes of non-ischemic characteristic [3]”. However, up to the present, these criteria are not always sufficient enough for example to the effect that they do not have to correspond with the clinical course of the disease [4]. According to the immunohistochemical analysis, which is preferred at present, myocarditis is diagnosed by the “presence of ≥ 14 leukocytes per mm² of the bioptically removed myocardium samples, including up to 4 monocytes or macrophages per mm² and ≥ 7 CD3+ T-lymphocytes per mm²” [5].

Author of the opening picture: Wapcaplet, Yaddah, Wnauta

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References:

1) RICHARDSON P., MCKENNA W., BRISTOW M., MAISCH B., MAUTNER B., O´CONNELL J., OLSEN E., THIENE G., GOODWIN J., GYARFAS I., MARTIN I., NORDER P. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation, 93(5), 841–842.

2) ELLIOTT P., ANDERSSON B., ARBUSTINI E., BILINSKA Z., CECCHI F., CHARRON P., DUBOURG O., KÜHL U., MAICH B., MCKENNA W.J., MOSERRAT L., PANKUWEIT S., RAPEZZI C., SEFEROVIC P., TAVAZZI L., KEREN A. Classification of the cardiomyopathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. European Heart Journal [online]. 2008, -(29), 270–276 [cit. 2016-08-10].

3) T., ARETZ et al. Myocarditis. A histopathologic definition and classification. The American Journal of Cardiovascular Pathology [online]. 1986, 1(1), 3-14 [cit. 2017-02-06].

4) AL-AQEEDI R.F., Chapter 2: Clinical Presentation. In: WILSON J. Clinical Handbook of Myocarditis. New Jersey: Foster Academics, 2015. pp. 33–69. ISBN: 978-1-63242-083-1.

5) MAISCH B., BÜLTMAN B., FACTOR S., GRÖNE H.-J. et al. World Heart Federation Consensus Conferences Definition of Inflammatory Cardiomyopathy (Myocarditis): Report from two Expert Committees on Histology and Viral Cardiomyopathy. Herz [online]. 2000, 25 (3), 200-209 [cit. 2016-08-26].

Příspěvek Definition of myocarditis and inflammatory cardiomyopathy (ICMP) pochází z Myokarditida

The effect of immunosuppressive therapy lies in the suppression of the immune system reaction. The possibilities to use immunosuppressants in the therapy of myocarditis and inflammatory dilated cardiomyopathy are influenced by the presence of the virus in the heart muscle tissue. In patients with detected genetical information of a virus in the heart muscle, immunosuppressive therapy cannot be indicated. It could even cause deterioration of a patient´s state of health.

For this reason, immunosuppressive therapy in indicated just in patients without the presence of the genetic information of the virus in the heart muscle. It is also indicated in certain types of myocarditis like for example giant cell and hypersensitive eosinophilic myocarditis or in myocarditis connected with systematic disorders.

For the indication of the immunosuppressive therapy, the results of the endomyocardial biopsy are crucial.

This specific research had two parts – so-called retrospective (there were investigated cases “from past”) and prospective (patients were studied “in present”). The effect of immunosuppressive therapy was investigated in patients with chronic myocarditis and inflammatory cardiomyopathy (see this article). In these studies, patients were categorized into two groups – one got immunosuppressive therapy (specifically prednisone and azathioprine) and the other got placebo and standard heart failure therapy.

In most of the patients in the groups that got immunosuppressants, there was observed improvement of the heart function in both studies. Ejection fraction of the left ventricle increased and dilatation (“enlargement”) of the heart chambers decreased. In the group of patients with placebo, their state of health remained the same or got worse.

Authors of this research tried to explain the effect of immunosuppressant at the cellular level. In their conclusion, they presume that the improvement of patients´ state of health after immunosuppressive therapy was caused by the suppression of degradation and cell death, of activation of cellular proliferation (increase in cell numbers) and the production of new cellular components (contractile elements) important for the right function and contractility of the heart.

Therapy with immunosuppressants takes place in specialized centres. Currently, there is a study in General University Hospital investigating the effect of immunosuppressive therapy in inflammatory cardiomyopathy.

Author of the opening picture: Edelhart~commonswiki

Příspěvek Immunosuppressive therapy of myocarditis pochází z Myokarditida

Could you please share with us some information about your professional life?

In 1999, I have successfully graduated from the 2nd Medical School of Charles University in Prague. After studies, I have spent a year as a PhD student on the Department of Medical Informatics and afterwards, I have spent 1,5 years on the substitute “civilian” military service. Then, in 2002, I have commenced in the Department of Radiology of the 2nd Medical School of Charles University and Motol Hospital. Except the 2-year intermezzo, when I have worked in a hospital in southern Scotland (Dufries, 2012-2014), I am a doctor on the Department of Radiology in Motol Hospital up to now.

What is currently the significance of cardiac magnetic resonance in the diagnosis of myocarditis?

Magnetic resonance is not absolutely necessary for the diagnosis of myocarditis, however, its importance is increasing gradually. Firstly, it can help to distinguish myocarditis from other diseases of the heart muscle. Secondly, it can display, if there is just an inflammation in the myocardium or if it happened, that irreversibly damaged heart muscle cells have been replaced by a scar. Furthermore, magnetic resonance is a reliable method for the evaluation of the heart ventricles function which is often decreased in myocarditis.

What benefits it brings?

The biggest advantage of the magnetic resonance is that it is non-invasive and without radiation load. Thanks to the fact that it determines the localization of the biggest damage to the heart muscle, it can help during invasive sampling of the heart muscle tissue (endomyocardial biopsy) if this examination is necessary. Further, the extent of the damaged displayed on magnetic resonance helps to determine prognosis, so what will be the progress of the disease. When the magnetic resonance examination is repeated, this progress may be evaluated.

A news in the magnetic resonance is so-called T2-mapping. Could you please tell us more about that?

T2 and also T1 mapping are not completely new methods, however their significance and utilization in heart imaging increases. Mapping is based on basic parameters of magnetic resonance imaging and it enables qualitative evaluation with the determination of T1 and T2 relaxing times in the certain tissue. These parameters are different in the healthy and sick myocardium. In recent years, a number of scientific studies using this mapping for the evaluation of myocarditis increases. T2 mapping is useful primarily for the situation, where oedema of the myocardium is diffuse (equally in the heart muscle) and it is difficult to evaluate it clearly visually.

Is there also some other news in the diagnosis of myocarditis in the question of imaging methods?

Newly used and researched method is T1 mapping, which, as it seems, enables more accurate determination of fibrous changes including general ones, which are difficult to be determined by traditional methods like late enhancement.

What is your opinion about the website www.myokarditida.cz? Would you recommend it? Alternatively, for whom do you think it could be beneficial?

The version for public dealing with the issue of different diseases are quite common abroad and so there are accessible in foreign languages (mostly in English). Website www.myokarditide.cz are also in the Czech language, and therefore they could be and an important source of information for Czech patients and their relatives. Considering the extent and depth of information, there could be interesting not just for non-professionals, but also for medical staff which do not come often in contact with myocarditis.

Příspěvek Theodor Adla M.D. pochází z Myokarditida

After the discharge, a long convalescence, regular check-ups in cardiology, Holter monitoring, rest and small walks had come after. Luckily, summer holidays had come very soon, so I had a plenty of time for rest and healing. Step by step, I had forgotten about myocarditis and I had had no idea that I could meet with this diagnosis even in another time.

Another summer holidays had come and again in the rest regime, because I had fallen from stairs and bruised my leg the last week of the school year. Few days before the end of holidays, I had felt again in the evening tired and it seemed to me that I had a strange “inner heat”. At 4 am, a chest pain had woken me up and I had had a short of breath. We had called an ambulance again. They were not very willing, but eventually they had decided to take me to the hospital. An hour later we had found out that I had again increased level of troponin, meanwhile just a little bit. So, for me a good known “trip” in cardiology and in a bed with a monitor had followed. I had a suspect that it was going to be another myocarditis, but it did not occur to me anyway that it was going to pick up such speed. I had strong and unbearable chest pain in the night. The following day in the morning, troponin level was 8,8 and the day after 9,6. They had transported me closer to the cardio centre, just for sure. I did not protest, because there was an air condition, a better bad and good TV. That time I had undergone cardiac magnetic resonance, where the diagnosis of myocarditis was confirmed and it also showed an oedema of the left ventricle.

I had lucky in both cases and I believe that I have helped this a lot with truly strict observance of the rest regime and instructions of my physicians. I have managed both myocarditis without a damage to the heart function. I will be permanently observed in cardiology, I will have some restrictions for the rest of my life, however, I have a chance that other myocarditis will not come and that I will be able to live a normal life, study medicine and become a physician.

Příspěvek My story pochází z Myokarditida

Interferons, including interferon beta, are a part of anti-viral and anti-cancer immunity. They suppress the reproduction of the virus and cause cell death in cells affected by the virus.

Up to now performed researches were not of larger scales and the principle of interferon beta effect administered to patients with myocarditis was not still clarified. The results are, however (at least in some types of myocarditis), very promising. There is even an assumption that the administration of interferon beta could be beneficial even in patients suffering from the chronic form of myocarditis.

In study Kühl et al. 2003, a group of patients with persisting heart muscle inflammation caused by enteroviruses and adenoviruses was treated with interferon beta (specifically interferon beta 1a) for 6 months. The results proved complete elimination of both groups of viruses from the heart muscle, their heart chamber dimensions decreased, symptoms of the heart failure improved and generally, there was observed a significant improvement of patients´ state of health.

Interferon was administered subcutaneously in gradually rising doses. The side effects of the interferon administration were fatigue, flu-like symptoms, reddening in the area of the puncture. These symptoms disappeared in four weeks.

Some patients complained about the feeling of general worsening of their state of health. These feelings subsided after the 12^th week of the therapy.

The effect of interferon beta was researched even in herpetic viruses parvovirus B19 and human herpesvirus 6 (HHV-6). In this case, complete elimination of the virus was not observed and interferon had not such effects like in patients with myocarditis caused by enteroviruses and adenoviruses. Nevertheless, even in the group of patients with herpetic viruses, improvement of their state of health was observed.

The release of interferon beta in common treatment algorithm in myocarditis cases is complicated by a low number of large studies, by the fact that different viruses may respond to the therapy differently and by other factors. Up to now, it is not completely clearly known which mechanisms are influenced by interferon beta. Nevertheless, there is a presumption that at least, the therapy with interferon could prevent further progress of the disease.

Author of the opening picture: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute

Příspěvek Treatment with interferon beta pochází z Myokarditida

Příspěvek Dictionary pochází z Myokarditida

Now I am going to describe to you, what´ s actually going on in the body during the myocarditis. The heart wall is composed of three layers – the endocardium (the inner heart layer membrane), the myocardium (the heart muscle) and the epicardium (the external heart membrane). The heart is placed in a sacculated case called the pericardium (picture 1). During myocarditis, the myocardium (heart muscle) is affected.

Picture 1: Heart wall (author: BruceBlaus)

The most common causes of myocarditis are different kinds of viruses and each of them damages the heart in different way. Less often myocarditis can be cause by bacterium, fungi, parasites, toxins, drugs or myocarditis can be a complication of another, mostly autoimmune disease, see this page). During viral myocarditis, the heart damage is developing during several successive phases and the patient can pass through up to three phases of the disease. The first phase of myocarditis is associated with viremia, when cells of the heart muscle are damaged by the virus itself. The virus affects the heart muscle cells or the cells of vessels nearby. The virus uses them for its replication and in the process, damages and destroys them. The second phase of the disease comes after several days (ca 4 days) from viremia. The immune system detects the virus and is stimulated by its presence in the heart muscle. It could sometimes induce a massive immune inflammatory response, when the immune response includes cell (white blood cells) and antibody-mediated immunity. There are several kinds of cells connected to the immune response – macrophages, activating the cytokines release (e.g. interleukins –mediating the communication between cells of immune system, and chemokines – controlling the transport of cells of immune system to the place of inflammation). Further, there are NK-cells, destroying cells affected by the virus. There are also T and B-cells, participating in the antibodies production and the elimination of heart muscle cells which have been attacked by the virus. The heart muscle is also damaged by the immune reaction, but is the price that must be paid to stop the replication of virus infection. In some cases, the immune system can “cause” the most part of the damage in the heart muscle.

Picture 2: Scheme of myocarditis (authors of the pictures: Thomas Splettstoesser; Wapcaplet; KGH)

  After the elimination of the virus or after the demarcation of heart muscle cells affected by virus, the immune system must “calm down” as soon as possible. There are several mechanisms participating in this situation. If the immune system did not “calm down,” it could move on to the state of chronic stimulation or autoimmune response (“self-destruction”), and could continue damaging the heart. It causes the formation of fibrosis (scars) in the heart muscle, with continuing chronic inflammation. It causes heart structural changes and a worsening of the myocardium function. It can lead to the development of other (systematic – autoimmune inflammatory) disorders. The first 90 days from viremia are the most important in the processes mentioned above and also in the process of healing the affected parts of the myocardium and in the process of inhibition of immune response. It is also the time, when myocarditis could develop to the chronic form. The immoderate immune response is the reason, why a part of the treatment is focused on the immune regulation and the suppression of the immoderate immune response. The interaction between the immune system and the virus and the activity of the virus in the heart sometimes affects the heart´s function, which could change during the acute inflammation. The changes in function are mostly observed at the left ventricle (Picture 3). The changes manifest with different disorders of heart rhythm (arrhythmias) and in some cases even with symptoms of heart failure. The pericardial effusion (accumulation of fluid between the membranes of pericardium) is observed in around one half of cases. The accumulated fluid could “press” on the heart, what makes primarily the filling of the heart with blood more difficult. The blood supply to the right atrium and right ventricle is decreased and then also adequate pumping of blood to the body. Sometimes the heart tamponade can be observed – it is cause by enormous accumulation of fluid and a noticeable worsening of the heart function. The effusion is caused by inflammation of the pericardium (pericarditis), because of that; myocarditis accompanied with the inflammation of pericardium is called myopericarditis. Vice versa, if the inflammation of the heart muscle (mostly weak) is a complication by pericarditis, we call this disease perimyocarditis. The course of myocarditis can be influenced even by genetic predisposition and gender. It was found, that myocarditis is more frequently observed at males than at females, probably because of testosterone. Sometimes, the virus is not completely destroyed by the immune system and then it remains encased in the heart muscle. Or the virus is completely destroyed, but a weak inflammation persists in the myocardium. In some cases, both the virus and the weak inflammation of the myocardium can persist in the heart. Myocarditis can progress to a chronic form, when the other attack of the disease is possible.

Picture 3: Human heart (author: Wapcaplet, Yaddah, Wnauta)

THE COURSE AND COMPLICATIONS OF MYOCARDITIS (CLINICAL PICTURE OF MYOCARDITIS)

The course of myocarditis is different for each patient. Myocarditis can even pass without early diagnosis on the part of the patient and it can seem to be a “severe” flu to the patients and doctors. Diagnosis can unfortunately be made several weeks after the basic disease; when it progress to chronic phases, alternatively long-term complications. In some cases, diagnosis of myocarditis is not made at all, when the course of the disease is light. Sometimes, myocarditis can have very dramatic course, when the heart muscle inflammation causes changes in the heart function. It sometimes leads to severe disorders of heart rhythm and symptoms of heart failure. If the diagnosis of myocarditis has been provided  to you orone of your relatives, it is essential and indispensable to strictly followe the recommendation of medical experts. Maintain a strict resting regime and absolute mental peace. For half of the patients, myocarditis is healed without any severe consequences and another attack does not happen again. In some cases, the inflammation of the myocardium progress to the chronic form, often accompanied with limitation of the heart function (see this page). Chronic myocarditis is sometimes called inflammatory cardiomyopathy. Inflammatory cardiomyopathy has the same course as dilated cardiomyopathy, when dilatation – widening of  the heart ventricles is observed. Because of the persistence of the inflammation, fibrosis and damage of the heart muscle, structural changes of heart wall shows up and there are also changes in the reduction of heart contractility and suppleness of the heart wall. It leads to heart function disorder (mostly of the left ventricle). But it does not lead to additional necrosis of heart muscle cells. However, of course, there is a possibility of another attack of acute myocarditis.

Příspěvek What´s going on in the body (pathogenesis) pochází z Myokarditida

The rest regime means a restriction of physical exertion – e. g. do not lift heavy weights, purchase, do not do heavy garden work and generally do not do activities that make a patient tired and short of breath. The rest regime includes also the restriction of sport activities and other related activities for at least 6 months. It is possible to go for a short constitutional at the beginning. The time restriction of sport and higher physical exertion may last even longer than 6 months. It depends on the patient´s state of health, the heart function and decision of physicians.

The complications and changes to the heart´s function may appear even after a year after myocarditis, so in some patients it is recommended to continue in the rest regime even after 6 months after myocarditis itself.

The question of sexual life after myocarditis is also very individual. It depends on the patient´s state of health and her/his physical possibilities – there are some less and more strenuous sexual activities (a partner after myocarditis should not be exhausted).

The time of stay at home after the discharge from the hospital is individual and it depends on the consultation with a physician. It the patient´s employment is not highly physically strenuous; the home treatment lasts according to different medical resources from 1 to 3 months. In the first 3 months after the disease, the process of the inhibition of immune system activity and the healing of damaged heart muscle is taking place and the disease can pass to the chronic form (see Definition of myocarditis).

There are also many others measures that should be observed for a longer time, such as changes of the eating and life style. A patient after myocarditis should observe rational and varied diet and rules of healthy life style. It means for example to reduce amount of salt in food, avoid fat and greasy foods and reduce the intake of sweets. The patient should also reduce the consumption of alcohol which is in some cases even one of the cases of myocarditis. Smoking should be avoided too.

It is not true that myocarditis is not a disease of athletes. Myocarditis may affect anyone and it does not matter if she/he is and athlete or a “port layabout”. This disease is influenced by many factors which are independent on sport activities. By contrast, in athletes who overlook for a longer time the signs of myocarditis and try to “run off the disease and leave it untreated” and try to avoid a check-up at physicians may have myocarditis with more dramatic course, because physical strain in the beginning of the disease mostly leads to rapid deterioration of the patient´s state of health.

A part of the convalescence and prevention of myocarditis is to avoid meetings with people with a virus infection, including flu or other infectious disease (primarily of respiratory and digestive system, including diarrhoeal diseases). As protective tools a disinfectant of hands or in some cases surgical mask may be used. When the patient after myocarditis already has an infection, it is really important to treat it properly and do not leave the disease untreated.

It associates with a strict observance of hygiene, including mouth, because bacteria are also one of the causes of myocarditis.

It is also important to minimalize the exposure to ticks – wear long shirts and trousers and use an insect repellent. The best is to avoid trips in areas with a higher concentration of ticks.

Very important part of the convalescence is that patients should not overestimate their physical possibilities and should not hype themselves up for some risky behaviour. It could cause a severe damage to the patient after myocarditis. The prevention of myocarditis and other disease associates even with the observance of safe sex rules (e.g. condoms) and avoid the use of narcotics.

Vaccinations against infection diseases are also recommended. You can read in the article Causes that myocarditis may be caused by a huge number of agents and it could be advantageous to avoid them – at least in those infections where a vaccination exists.

Check-ups in physicians and sometimes so called ergometry are part of the convalescence. In the case of ergometry, a patient steps on a special bike and simultaneously his/her ECG is recorded. It shows physicians how the heart works during a work. Often a cooperation of physicians from different fields is needed – mostly from cardiology an immunology.

The most important part of the convalescence if self-discipline – observe the recommendations of physicians and observe the above-mentioned measures, rules and the rest regime in its total time. My personal recommendation is – the non-observance of these rules and other recommendations for at least 6 months is not worthy of potential, even lifelong complications. 6 months of the rest regime are better the lifelong problems and maybe even an absolute ban on some activities, including sports.

Myocarditis is often a severe disease, in some cases even life-threatening condition, unfortunately sometimes fatal and because of that it is not good to underestimate it.

Příspěvek Life with myocarditis pochází z Myokarditida