Myocarditis: Difference between revisions

Myocarditis can be caused by a variety of infectious and noninfectious illnesses (Table 1).

Most often, myocarditis results from common viral infections. In developed countries, the most frequently identified viruses were enteroviruses (including coxsackievirus) until the 1990s. Now parvovirus B19 and Human Herpes Virus 6 are the viruses most frequently found in patients with acute and chronic cardiomyopathy (Figure 1). PCR of endomyacardial biopsies in 624 patients (approximately 60% children)  with idiopathic heart failure and biopsy-proven myocarditis showed viral genomes in 38% of cases, whereas viral genomes could only be shown in 20% in myocarditis-negative biopsies of 149 patients with heart failure (J Am Coll Cardiol 2003 Aug 6;42(3):466-72). Interestingly, although adenovirus and enterovirus were the most encountered pathogens in both groups, PCR showed other pathogens only in the patients with biopsy-proven myocarditis. Some of these pathogens, especially Parvovirus B19 end Human Herpes Virus-6, were predominantly present in a more recent study, investigating only adult patients (Figure1). There are several potential mechanisms by which a viral myocarditis might cause acute or chronic DCM, including direct viral damage or as a result of humoral or cellular immune responses to persistent viral infection (Figure 2).Our understanding of the pathogenesis of viral myocarditis comes almost entirely from experimental models of acute coxsackie B virus infection. The initial change is myocyte damage in the absence of a cellular immune response. The myocyte injury may be mediated through direct viral toxicity, perforin-mediated cell lysis, and cytokine expression. The second phase which rapidly follows is an innate immune response comprised of altered regulatory T cell function, NK cells, interferon gamma, and nitric oxide. In the third phase, a heart specific immune response is characterized by antibodies to pathogen and host cardiac proteins and autoreactive T cells. Most subjects recover with few consequences, but a minority either die from arrhythmias or progress onto a phase of chronic heart failure. Hemodynamic and neurohumoral stresses lead to ventricular dilatation.

Idiopathic giant cell myocarditis is a rare, virulent, and frequently fatal type of myocarditis that may respond to immunosuppressive therapy. (Am J Cardiol. 2008 Dec 1;102(11):1535-9. Epub 2008 Sep 18.) The pathogenesis of this disorder is not known. In an animal model, a disorder similar to giant cell myocarditis was induced by immunization with cardiac myosin. In this model, myocardial damage is primarily mediated by T lymphocytes.

This is an autoimmune reaction in the heart that is often drug-related and is usually characterized by acute rash, fever, peripheral eosinophilia, and ECG abnormalities such as nonspecific ST segment changes or infarct patterns . However, some patients present with sudden death or rapidly progressive Heart Failure. The true incidence is unknown. One estimate comes from an autopsy study, which identified 16 cases in more than three thousand consecutive autopsies (<0.5 percent). In other series, the prevalence of clinically undetected HSM in explanted hearts ranged from 2.4 to 7 percent. HSM is usually temporally related to a recently initiated medication. Numerous drugs have been implicated (including methyldopa, hydrochlorothiazide, furosemide, ampicillin, tetracycline, azithromycin, aminophylline, phenytoin, benzodiazepines, and tricyclic antidepressants). However, myocarditis does not always develop early in the course of drug use. As an example, patients taking the antipsychotic agent clozapine have been reported to develop myocarditis more than two years after the drug was started. Eosinophilic myocarditis has also been seen in 2.4 to 23 percent of patients treated with dobutamine infusion. It is uncertain whether this reaction represents hypersensitivity to the drug itself or a reaction to sodium bisulfite, which is a preservative in many dobutamine preparations. It has been diagnosed either on endomyocardial biopsy or retrospectively after explantation of the native heart. In some cases, tapering or discontinuation of dobutamine infusion has resulted in diminution of the peripheral eosinophilia and histologic improvement. Histologically, HSM is usually characterized by an interstitial infiltrate with prominent eosinophils, but little myocyte necrosis. However, occasional patients with apparent drug hypersensitivity have giant cell myocarditis, granulomatous myocarditis, or necrotizing eosinophilic myocarditis. These disorders can usually be distinguished from hypersensitivity myocarditis only by endomyocardial biopsy.

It has been suggested that celiac disease, which is often clinically unsuspected, accounts for as many as 5 percent of patients with autoimmune myocarditis or idiopathic DCM. Autoimmune disorders occur with increased frequency in patients with celiac disease and may be related in part to antigen overload resulting from increased intestinal permeability.

This is a protozoan infection due to Trypanosoma cruzi; it is a major public health problem in endemic areas in many South American countries. Morbidity is primarily related to three problems: megaesophagus, megacolon, and cardiac disease. Chagas' myocarditis is by far the most common form of cardiomyopathy in Latin American countries. It is estimated that over 750 thousand years of productive life are lost annually, because of premature deaths due to this disorder. In the acute phase it is characterized by intense and diffuse myocarditis with mononuclear infiltrates. The most characteristic cardiac anatomic lesion in the chronic phase is the ventricular apical aneurysm which, in one series, was noted in 52 % of 1078 autopsied Chagasic patients (Br Heart J 1981 Oct;46(4):432-7).

Systemic lupus erythematosus, Wegener's granulomatosis, giant cell arteritis, Kawasaki disease and Takayasu arteritis may cause myocarditis. Among patients with lupus, myocarditis has been found in approximately 9 percent in clinical studies and 6 percent in echocardiography studies in which global hypokinesis is the suggestive finding.

Lyme disease is a multisystem disease caused by infection with Borrelia burgdorferi. Cardiac involvement occurs during the early disseminated phase of the disease, usually within weeks to a few months after infection. The clinical features of Lyme carditis include heart block related to dysfunction of the conduction system and decreased cardiac contractility due to myopericarditis. Carditis occurs in approximately 5 percent of untreated adults in the United States, particularly among men. Carditis is less frequent in Europe, affecting approximately 0.3 to 4.0 percent of untreated adults. This difference may be related to infection by different organisms. B. burgdorferi sensu stricto is responsible for all cases in the United States, whereas B. afzelii and B. garinii are responsible for many cases in Europe, although B. burgdorferi sensu stricto occurs there as well. Lyme myopericarditis is often self-limited and mild, leading to transient cardiomegaly or mild pericardial effusion. In most cases, it is asymptomatic and clinically inapparent. The most frequent manifestation of myocardial involvement in Lyme disease is nonspecific ST and T wave changes on the electrocardiogram . However, occasional patients develop symptomatic myocarditis with cardiac muscle dysfunction and/or associated pericarditis.

Myocarditis may occur as a complication of other cardiomyopathies including cardiac amyloidosis, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. In amyloidosis and hypertrophic cardiomyopathy, myocarditis may affect prognosis.

Figure 2 : mechanisms for cardiac injury in myocarditis

[[Image:Cardiac_injury_myocarditis.png]]

Figure 3 : Survival in fulminant myocarditis vs acute myocarditis

Table 2 : Clinical scenarios (N Engl J Med. 2009 Apr 9;360(15):1526-38)

==Diagnosis and treatment of myocarditis==

Table 3 : Indications for endomyocardial biopsy

Figure 3 : Virus-specific patterns of myocarditis at first presentation and during follow-up