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ORIGINAL ARTICLE
Year : 2008  |  Volume : 9  |  Issue : 4  |  Page : 137-141 Table of Contents     

Combined use of intravenous immune globulin and steroid for acute myocarditis in pediatric population


Department of Cardiology and Cardiovascular Surgery, Hamad Medical Corporation, Doha, Qatar

Date of Web Publication17-Jun-2010

Correspondence Address:
Saad Al-Saeed
Pediatric Section, Department of Cardiology & Cardiovascular Surgery, Hamad Medical Corporation, P.O. Box 3050, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


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   Abstract 

Introduction: The optimum treatment for acute viral myocarditis in pediatric population is unknown. Some studies have shown the beneficial effect of high dose intravenous immunoglobulin (IVIG) while other reports suggested the corticosteroid to be effective in the treatment of acute viral myocarditis. In this study, we present our experience with combined use of high dose IVIG and corticosteroid along with conventional antifailure treatment for clinical acute viral mypcarditis in pediatric population.
Method and Results: Thirteen patients were included in the study with the clinical diagnosis of acute viral myocardistis and reduced cardiac function ie fractional shortening of < 28%. In the study group, 53% were male and 46% female with median age of 12 months and were treated with high dose IVIG and corticosteroid. Left ventricular function, left ventricular end diastolic dimension (LVEDD) and degree of mitral regurgitation (MR) were assessed echocardiographically at presentation; at 6 weeks and then at 6 months follow-up. At 6 months follow-up, LV function normalized in 92% of the patients, LVEDD improved in 62% and 84.6% of the patients had insignificant MR.
Conclusion: Our data suggest that use of high dose IVIG in combination with corticosteroid is an effective treatment for acute viral myocarditis in pediatric population.

Keywords: myocarditis, immunoglobulin, steroid, viral, cardiomyopathy, ejection fraction


How to cite this article:
Al-Saeed S, Dilawar M. Combined use of intravenous immune globulin and steroid for acute myocarditis in pediatric population. Heart Views 2008;9:137-41

How to cite this URL:
Al-Saeed S, Dilawar M. Combined use of intravenous immune globulin and steroid for acute myocarditis in pediatric population. Heart Views [serial online] 2008 [cited 2019 Nov 13];9:137-41. Available from: http://www.heartviews.org/text.asp?2008/9/4/137/63832


   Introduction Top


Myocarditis is an inflammatory myocardial disease that occurs in all age groups [1] . Most cases of myocaditis are thought to be subclinical but it can manifest as fulminant or may lead to chronic heart failure [2] . Although the cause of myocarditis often remains unknown, large variety of infections, systemic diseases, drugs and toxins have been associated with the development of this disease. Viruses, bacteria, protozoa and even worms have been implicated as infectious agents [3] . It's well known that viruses are an important cause of myocarditis in North America and Europe, and the most common etiologic agents among viruses are enteroviruses and adenoviruses [4] . Initially, only selected viruses were identified by serologic demonstration of rising antibody titers in the serum during acute myocarditis and convalescence [5] . The enterovirus genome has also been identified in the myocardium of patients with myocarditis and dilated cardiomyopathy [6] . By polymerase chain reaction (PCR) or by PCR - single strand conformation polymorphism analysis, enterovirus and enterovirus like RNA sequences have been identified in endomyocardial biopsy specimens from the patients with clinically suspected myocorditis and from those with idiopathic dilated cardiomyopathy [7],[8].

Viral myocarditis patients may present with history of recent flue like or gastrointestinal symptoms. Laboratory evaluation may show leukocytosis and elevated acute phase reactants [9] . Radiography of the chest generally shows cardiomegally and the electrocardiogram may show arrhythmias, heart block, low voltage and T wave abnormalities. Echocardiogram typically shows left ventricular dilatation with dysfunction and secondary mitral valve regurgitation. Endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis despite its limited sensitivity and specificity [3].

In viral tis, myocardial damage is initially caused by the direct action of virus and subsequently by autoimmune processes triggered by that virus [10],[11] .

Based on infection and immune model of myocardial damage, attempts to treat viral tis using anti-inflamatory and immunosuppressive drugs have been tried. Unfortunately, controlled trials have been failed to provide convincing evidence of the efficacy of anti-inflammatory and immunosuppressive drugs such as corticosteroids, azathioprine and cyclosporine [12],[13] . High dose intravenous immunoglobulin (IVIG) has both antiviral and immune modulatory effects and is an important therapy for Kawasaki disease, a coronary vasculitis in children [14],[15] . Recently, treatment with high dose IVIG has been tried in patients with idiopathic myocarditis, dilated cardiomyopathy or peripartum cardiomyopathy and clinical improvement has been found in some cases [16] . In experimental murine viral myocarditis, antiviral therapy with alpha interferon or ribavirin had been effective only if started prior to or soon after viral infection [17],[18] , therefore antiviral therapy can be seldom applied in the clinical practice.

In this study, we present our experience with combined use of high dose IVIG and corticosteroid along with conventional antifailure treatment for clinical myocarditis in pediatric population.


   Methods and Materials Top


From April 2005 to July 2008, all the children admitted with the clinical diagnosis of viral myocarditis here at Hamad General Hospital, Doha - Qatar were retrospectively reviewed. Diagnosis of viral myocarditis was made if there was less than 3 month history of viral like illness along with symptoms and signs of congestive heart failure and echocardiogram had confirmed left ventricular dysfunction.

Patients with history of familial dilated cardiomyopathy, presence of significant structural heart disease leading to heart failure or documentation of conditions known to be associated with heart failure e.g. sepsis, metabolic disorder, Kawasaki disease, arrhythmias, and previous treatment with known cardiotoxic agents were excluded from the study.

The medical record was reviewed for clinical/laboratory data at the time of admission and then at 6 weeks and 6 months out-patient clinical and echocardiographic follow up of the indexed cases. Left ventricular function and dimension in the form of fractional shortening (FS) and left ventricular end diastolic dimension (LVEDD) were evaluated by 2-D and M mode, and valvular regurgitation by color Doppler echocardiography. Fractional shortening of more than or equal to 28% was considered as normal and LVEDD was considered as dilated if the dimension was more than upper limit of normal for that age group. After establishing the diagnosis of viral myocarditis, a single dose of 2 gm/kg of IVIG was administered over 12-24 hours and corticosteroid was given as per protocol.


   Steroids protocol Top


  • Intravenous methylprednisone: 10 mg/kg/day divided in to twice daily doses for 3 days.
  • Then oral prednisone: 2 mg//kg/day divided in to twice daily doses for 3 days.
  • Then start weaning prednisone by decreasing it 0.2 mg/kg bi-weekly till it's completely weaned off. With this protocol, the total course of steroid would be about 6 weeks. If there is cardiac function improvement but deterioration occurs during weaning period of steroid, then go back to the dose where function got better, keep that dose for one week and then start weaning again. Anti-failure drugs including inotropes, diuretics, afterload reducing agents and anti-platelet agents were given according to the patient's clinical status.

   Results Top


Between April 2005 and July 2008, total of twenty patients were admitted to Hamad General Hospital with clinical diagnosis of myocarditis. Fifteen out of 20 (75%) were admitted to pediatric intensive care and 5 (25%) patients were admitted to pediatric floor. Seven patients were excluded from the study group because they did not fulfill the inclusion criteria. One of these 7 patients was 3 months old, found to have severe hypocalcaemia and cardiac function recovered after normalization of calcium level, 2nd patient was 1 year old with history of familial dilated cardiomyopathy, 3rd patient was 14 years old who had muscle tumor at 2 years of age, was treated with chemotherapy and now developed dilated cardiomyopathy after a decade of latent period, 4th patient was 13 years old with ectopic atrial tachycardia and cardiac function normalized after arrhythmia control, 5th patient was 1 month old with anolamous left coronary artery from pulmonary artery (ALCAPA), the 6th patient was 10 months old also a case of ALCAPA, and the 7 th patient was 2 weeks old with history suggestive of inborn error of metabolism.

Thirteen patients [Table 1] were included in the study, 53% were boys and 46% girls. Out of these 13 patients, 6 (46%) were Qataris and 7 (53%) were non-Qataris. Median age at presentation was 12 months with range of 1 month - 6.5 years and median weight was 10 kg with range of 3.6 to 19.5 kg. The median duration of symptoms before admission was 3 days with range of 1 day - 3 months. General presentation and chief complaints of the indexed cases are shown in [Table 2].

Fractional shortening was with range of 7%-24% at the time of admission; at 6 weeks follow-up, 6 out of 13 (46%) patients had normal FS, ie > 28% and at 6 months follow-up, 12 out of 13 (92%) patients had normal FS [Graph 1] [Additional file 1] . The only patient who didn't improve was case no. 11 [Table 1] who kept on deteriorating till he died with severe left ventricular dysfunction. LVEDD was dilated in 12 (92%) patients at the time of diagnosis of myocarditis. At 6 weeks and 6 months follow-up, LVEDD remained dilated in 9 (69%) and 4 (31%) patients respectively. At presentation, 3 patients had severe mitral regurgitation (MR), 2 moderate to severe, 5 moderate, 1 mild to moderate and 2 patients had mild MR. At 6 weeks follow up, 2 patients had moderate to severe mitral regurgitation, 4 had moderate, 1 patient had trivial while 6 patients had no residual mitral regurgitation. At 6 months, 1 patient had severe mitral regurge, 1 patient had mild, 3 patients had trivial and 8 patients had no residual miltral regurgitation [Graph 2] [Additional file 2] .


   Discussion Top


Viral myocarditis is one of the known causes of ventricular dysfunction. The role of anti-inflamatory and immuno-suppressive drugs in viral myocarditis is debatable and no randomized trials are available in pediatric population. K J Lee et-al. [19] found cortosteroids to be beneficial for the treatment of acute myocarditis in children. In studies by Nancy Drucker et-al. [20] and McNamara et-al. [21] , intravenous gamma globulin was found to be effective for the treatment of acute myocarditis. However, in a study by Bobert English et-al. [22] , the addition of intravenous immuneglobulin to steroid when treating acute myocarditis provided no added benefit in terms of overall survival or time to recovery of normal left ventricular function and also neither of these immunomodulatory approaches appeared to confirm a significant survival benefit over supportive care alone.

In our study, we tried a combination of intravenous immunoglobulin (IVIG) and steroid in clinical viral myocarditis. Left ventricular function normalized in 46% cases at 6 weeks and in 92% of the myocarditis patients at 6 months follow-up. LVEDD was significantly reduced at 6 weeks and further reduction was noticed at 6 months follow-up. Mitral regurgitation was also dramatically improved at these follow-ups. After initial improvement, none of the patients deteriorated in our study group. We therefore conclude that combination of IVIG and steroid used with our protocol is a useful treatment for viral myocarditis. However, large number of patients with biopsy proven myocarditis need to be treated with this regimen before making final recommendations.

Steroid protocol: Courtesy of Prof. Henry Wiles, Chief of Pediatric Cardiology, Augusta -Georgia, USA.

 
   References Top

1.Richardson P, Mckenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Oslen E, Thiene G, Goodwin J, Gyrfas I, Martin I, Nordef P. Report of the 1995 World Health Organization/International Society and federation of Cardiology Task Force on the definition and classification of Cardiomyopathies. Circulation 1996, 93:841-842.   Back to cited text no. 1      
2.Levi D, Alejoes J: Diagnosis and treatment of Pediatric viral myocarditis, Curr Opin Cardiol 2001, 16:77-83.  Back to cited text no. 2      
3.Arthur M. Feldman, MD, PH.D; Dennis McNamara, MD. Review article, Myocarditis. The New England Journal of Medicine 2000; 1388-1389.  Back to cited text no. 3      
4.Joan L Robinson, Lisa Hartling, Ellen Crumley, Ben Vandermeer, and Terry P Klassen. A systematic review of intravenous gamma globulin for therapy of acute myocarditis. BMC Cardiovascular Disorders 2005, 5:12.   Back to cited text no. 4      
5.Cambridge G, Mac Arthur CG, Waterson AP, Goodwin JF, Oakley CM. Antibodies to Coxsacki B viruses in Congestive Cardiomyopathy. Br Heart J 1979; 41:692-696.  Back to cited text no. 5      
6.Bowles NE, Richardson PJ, Olsen EGJ, Archard LC, Detection of Coxsackic -B-virus specific RNA sequences in myocardial biopsy samples from patient with myocarditis and dilated cardiomyopathy, Loncet 1986; 1:1120-1123.  Back to cited text no. 6      
7.Jin O. Sole MJ, Butany JW, et al. Detection of enterovirus RNA in myocardial biopsies from patient with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 1990; 82:8-16.  Back to cited text no. 7      
8.Schwaiger A, Umlauft F, Weyver K, et al. Detection of entiroviral ribonucleic acid in myocardial biopsies from patients with idiopathic dilated cardiomyopathy by polymerase chain reaction. Am Heart J 1993; 126:406-410.   Back to cited text no. 8      
9.Vignola PA, Aonuma K, Swaye PS, et al. lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnose with endomyocardial biopsy and response to immunosuppression. J AM Coll Cardiol 1984; 4:812-9.  Back to cited text no. 9      
10.Knowlton KU, Badorff C. The immune system in viral myocarditis maintaining the balance, Circ Res 1999; 85:559-561.  Back to cited text no. 10      
11.Liu P, Martino T, Opavsky MA, Penninger J. Viral myocarditis : balance between viral infection and immune response. Con J Cardiol 1996; 12:935-943.   Back to cited text no. 11      
12.Parrillo IE, Cunnion RE, Epstein SE et al. A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med 1989; 321: 1061-1068.  Back to cited text no. 12      
13.Mason JW, O'Connel JB, Herkowitz A et al. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 1995; 333: 269-75.  Back to cited text no. 13      
14.Dennis M. McNamara, Richard Holubkov, Randall C. Starling, G. William Dec, Evan Loh, Guillermo Torre-Amione, Alan Gass, Karen Janosko, Tammy Tokarczyk, Paul Kessler, Douglas L. Mann and Arthur M. Feldman. Controlled Trial of Intravenous Immune Globulin in Recent-Onset Dilated cardiomyopathy. Circulation 2001; 103; 2254-2259.  Back to cited text no. 14      
15.Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 1986; 315:341-347.  Back to cited text no. 15      
16.A. Tedeschi, L. Airaghi, S. Giannini, L. Ciceri & F.M. Massari. High-dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the literature. Journal of Internal Medicine. Volume 251 Issue 2 Page 169 - February 2002.  Back to cited text no. 16      
17.Matsumari A, Tomioka N, Kawai C, Protective effect of recombinant alphainterferon on Coxsadcievirus B3 myocarditis in mice. AM Heart J 1988; 115:1229-1232.  Back to cited text no. 17      
18.Kishimoto C, Crumpacker CS, Abelmann WH. Ribavirin treatment of murine coxsackievirus B3 myocarditis with analysis of lymphocyte subset. J Am Coll Cardiol 1988; 12:1334-1341.  Back to cited text no. 18      
19.K J Lee, B W McCrindle, D J Bohn, G J Wilson, G P Taylor, R M Freedom, J F Smallhorn, L N Benson. Clinical outcomes of acute myocarditis in childhood. Heart 1999;82:226-233.  Back to cited text no. 19      
20.Nancy A. Drucker, MD; Steven D.Colan, MD; Alan B. Lewis, MD; Alexa S. Beiser, PhD; David l. Wessel, MD; Masato Takahashi, MD; Annette L. Baker, RN, MSN; Antonio R. Perez-Atayde, MD; Jane W. Newburger, MD, MPH. Gamma Globulin Treatment of Acute Myocarditis in the Pediatric Population. Circulation, 1994, 89: 252-257.  Back to cited text no. 20      
21.Dennis M. McNamara, MD; Warren D. Rosenblum, MD; Karen M. Janosko, MSN; Mary K. Trost, CRNP; Flordeliza S. Villaneuva, MD; A.J. Demetris, MD; Srinivas Murali., MD;Arthur M. Feldman, MD, PhD. Intravenous Immune Globulin in the Therapy of Myocarditis and Acute Cardiomyopathy. Circulation 1997;95:2476.  Back to cited text no. 21      
22.Robert F. English, Jannie E. Janosky, Jose A. Ettedgui, Steven A. Webber. Outcomes for children with acute myocarditis. Cardiol Young 2004; 14:488-493.  Back to cited text no. 22      



 
 
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    Methods and Mate...
    Steroids protocol
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