Correspondence
Myocarditis
N Engl J Med 2009; 361:422-424July 23, 2009
- Article
To the Editor:
Supportive care is the mainstay of therapy for acute myocarditis. In his review article on this topic, Cooper (April 9 issue)1 notes that studies of immunosuppressive therapy have not shown a clear beneficial role, as compared with usual care. Thus, the beneficial effect of immunosuppressive therapy remains controversial. Treatment that is based on the presence of human leukocyte antigen may be associated with improved outcomes.1 However, are there other ways to predict who is likely to benefit from immunosuppressive therapy? In one trial, prednisolone that was administered to patients who did not have a response to other treatment or whose clinical condition worsened with virus-negative inflammation had the best clinical and echocardiographic outcomes.2 In another study of patients with myocarditis in whom conventional supportive therapy failed, the overwhelming majority of those who did not have a response to immunosuppressive therapy were found to have viral genomes in biopsy specimens and no cardiac autoantibodies.3 The authors of that study concluded that patients “with circulating cardiac autoantibodies and no viral genome in the myocardium are the most likely to benefit from immunosuppression.”3 Thus, physicians should be aware of studies suggesting that patients with virus-negative myocarditis may benefit from immunosuppressive therapy.
3 ReferencesJohn R. Kapoor, M.D., Ph.D.
Stanford University, Stanford, CA 943051
Cooper LT Jr . Myocarditis. N Engl J Med 2009;360:1526-1538
Full Text | Web of Science | Medline2
Zimmermann O ,Kochs M ,Zwaka TP , et al. Myocardial biopsy based classification and treatment in patients with dilated cardiomyopathy. Int J Cardiol 2005;104:92-100
CrossRef | Web of Science | Medline3
Frustaci A ,Chimenti C ,Calabrese F ,Pieroni M ,Thiene G ,Maseri A . Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders. Circulation 2003;107:857-863
CrossRef | Web of Science | Medline
To the Editor:
Cooper describes several causes of myocarditis that include a number of viruses, Borrelia burgdorferi, Trypanosoma cruzi, and other infectious agents. There are additional causes of myocarditis that are not discussed. For example, Corynebacterium diphtheriae also can cause myocarditis.1 Infection with Campylobacter jejuni, the most common cause of human bacterial enteritis in developed countries, can be associated with myocarditis, as can salmonella infection.2 Anticancer drugs can cause cardiac side effects, ranging from arrhythmias to alterations in coronary vasomotion, leading to myocardial ischemia and myocarditis with potentially fatal outcomes. Anthracyclines are potent chemotherapeutic agents associated with various forms of cardiomyopathy. Acute cardiomyopathy is seen within 3 months after drug exposure and may take the form of either a reversible myocarditis and pericarditis or chronic cardiomyopathy with either an early or a late onset.3 These aspects should have been mentioned in the article. Besides the medical treatments for myocarditis that Cooper describes, levosimendan, a positive inotropic drug, has been shown to have beneficial effects on clinical and hemodynamic results in patients with acute decompensated heart failure from myocarditis.4
4 ReferencesSebastian Szabo, M.D.
Kardiologische Gemeinschaftspraxis, 40764 Langenfeld, Germany
krisztinaszb@aol.com Thomas Oikonomopoulos, M.D.
Hans Martin Hoffmeister, M.D., Ph.D.
Städtisches Klinikum Solingen, 42653 Solingen, Germany1
Havaldar PV ,Sankpal MN ,Doddannavar RP . Diphtheritic myocarditis: clinical and laboratory parameters of prognosis and fatal outcome. Ann Trop Paediatr 2000;20:209-215
Web of Science | Medline2
Hannu T ,Mattila L ,Rautelin H ,Siitonen A ,Leirisalo-Repo M . Three cases of cardiac complications associated with Campylobacter jejuni infection and review of the literature. Eur J Clin Microbiol Infect Dis 2005;24:619-622
CrossRef | Web of Science | Medline3
Simmons A ,Vacek JL ,Meyers D . Anthracycline-induced cardiomyopathy. Postgrad Med 2008;120:67-72
CrossRef | Web of Science | Medline4
de March Ronsoni R, Feijó RV Jr, Melo LH, et al. The use of levosimendan for myocardiopathy due to acute Chagas' disease. Int J Cardiol 2008 July 26 (Epub ahead of print).
To the Editor:
In his comprehensive review, Cooper does not mention acute rheumatic fever as one of the causes of myocarditis. This disease is an important cause of death and complications from cardiac causes. Acute rheumatic fever is diagnosed in about half a million patients worldwide every year; of these patients, rheumatic heart disease develops in approximately 300,000. This disease is associated with some 233,000 deaths annually.1 The estimated annual incidence of acute rheumatic fever varies from 374 per 100,000 in the indigenous population of Australia and New Zealand to less than 1 per 100,000 in high-income countries.2
There have been several outbreaks of acute rheumatic fever in middle-class populations in the Salt Lake City region since the mid-1980s.2 The disease has not been eradicated yet in the world, and its diagnosis remains a clinical challenge.
2 ReferencesHussam Ammar, M.D.
Erie County Medical Center, Buffalo, NY 14215Ragai Fouda, M.D.
Bassetlaw Hospital, Worksop S81 0BD, United Kingdom1
Carapetis JR ,McDonald M ,Wilson NJ . Acute rheumatic fever. Lancet 2005;366:155-168
CrossRef | Web of Science | Medline2
Cilliers AM . Rheumatic fever and its management. BMJ 2006;333:1153-1156
CrossRef | Web of Science | Medline
Author/Editor Response
Kapoor writes about immunosuppressive therapy for myocarditis. Deciding which patients with myocarditis may respond to immunosuppressive therapy first requires knowledge of the patient's clinical situation. Most patients improve with usual care in the common scenario of acute, mild-to-moderate dilated cardiomyopathy without high-degree heart block or hemodynamically significant ventricular arrhythmias. A cardiac biopsy is seldom needed in this clinical scenario, because histologic results rarely have a meaningful effect on the patient's prognosis or treatment.1 In contrast, two small, randomized trials suggested that patients with symptomatic, subacute-to-chronic dilated cardiomyopathy whose condition did not improve despite optimal medical management may benefit from a short course of immunosuppression if additional features of altered immunity are present.2,3 Investigators have used circulating antimyocardial antibodies, HLA expression on cardiomyocytes, and inflammatory cell–specific immunocytochemical stains to identify responsive populations with subacute-to-chronic dilated cardiomyopathy.4 It is not known whether the presence of viral genomes in the heart can identify a population with dilated cardiomyopathy that would not improve with immunosuppression. Patients with viral genomes that were detected on cardiac biopsy were excluded from the recently reported Tailored Immunosuppression in Inflammatory Cardiomyopathy (TIMIC) trial.3 Multicenter, randomized trials are still needed to assess the effect of immunosuppression on clinically meaningful end points, such as the rate of death and heart transplantation in patients with chronic, persistently symptomatic dilated cardiomyopathy.
I strongly agree with Szabo et al. that specific infections and toxins contribute substantially to the burden of myocarditis, particularly in the developing world. Since many of these specific causes have been addressed in other recent review articles, I chose to use the limited space in my article to focus primarily on viral and select noninfectious, autoimmune cardiac conditions. The authors cite a letter to the Editor concerning two patients with Chagas' cardiomyopathy who responded to levosimendan. At this time, the use of levosimendan for myocarditis is not established.
I agree with Ammar and Fouda that carditis from post-streptococcal rheumatic fever is a major cause of cardiomyopathy, particularly in the developing world. Frequently the long-term effects of post-streptococcal endocarditis, including atrial fibrillation and stroke, garner more attention than the long-term effects of myocarditis in this disorder. The Gates Foundation is sponsoring an ongoing project on the Global Burden of Disease that should help to separate the long-term morbidity of rheumatic carditis on the basis of major sequelae, including dilated cardiomyopathy.
4 ReferencesLeslie T. Cooper, Jr., M.D.
Mayo Clinic, Rochester, MN 55905
cooper.leslie@mayo. edu 1
Cooper LT ,Baughman KL ,Feldman AM , et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 2007;116:2216-2233
CrossRef | Web of Science | Medline2
Wojnicz R ,Nowalany-Kozielska E ,Wojciechowska C , et al. Randomized, placebo-controlled study for the treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation 2001;104:39-45
CrossRef | Web of Science | Medline3
Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J (in press).
4
Cooper L. The heat is off: immunosuppression for myocarditis revisited. Eur Heart J (in press).
