Heart 2000;84:449–454 Diagnosis is easiest during epidemics of cox- GENERAL CARDIOLOGY sackie infections but diYcult in isolated cases. Heart: first published as 10.1136/heart.84.4.449 on 1 October 2000. Downloaded from These are not seen by cardiologists unless they develop arrhythmia, collapse or suVer chest Myocarditis, pericarditis and other pain, the majority being dealt with in the primary care system. pericardial diseases Acute onset of chest pain is usual and may mimic myocardial infarction or be associated 449 Celia M Oakley with pericarditis. Arrhythmias or conduction Imperial College School of Medicine, Hammersmith Hospital, disturbances may be life threatening despite London, UK only mild focal injury, whereas more wide- spread inflammation is necessary before car- diac dysfunction is suYcient to cause symp- his article discusses the diagnosis and toms. management of myocarditis and peri- Tcarditis (both acute and recurrent), as Investigations well as other pericardial diseases. The ECG may show sinus tachycardia, focal or generalised abnormality, ST segment eleva- tion, fascicular blocks or atrioventricular con- Myocarditis duction disturbances. Although the ECG abnormalities are non-specific, the ECG has Myocarditis is the term used to indicate acute the virtue of drawing attention to the heart and infective, toxic or autoimmune inflammation of leading to echocardiographic and other investi- the heart. Reversible toxic myocarditis occurs gations. Echocardiography may reveal segmen- in diphtheria and sometimes in infective endo- tal or generalised wall motion abnormalities or carditis when autoimmune mechanisms may a pericardial eVusion. Echocardiography allows also contribute. Persistent viral infection of the other causes of heart failure to be excluded but myocardium was first demonstrated a decade pronounced focal changes in wall motion may ago.1 Slow growing organisms such as chlamy- lead to confusion with myocardial infarction, especially if the ECG changes also suggest dia and trypanosomal infection in Chagas’ dis- 5 ease are causes of chronic myocarditis. Non- this. infective causes in sarcoidosis and the collagen The chest x ray may be normal, show cardiac vascular diseases need to be sought. enlargement, pulmonary venous congestion or Acute myocarditis and acute pericarditis are pleural eVusions. not always associated (likewise meningitis and Evidence of myocyte necrosis may be found encephalitis do not always occur together) and with an increase in creatine kinase or appear- the clinical emphasis is usually on one or the ance of troponin, indicating myocytolysis. The http://heart.bmj.com/ other. highest enzyme concentrations occur early and will probably have returned to normal by about Myocarditis can be caused by many diVerent 6 viruses and the microbial pathogenesis may be a week after onset. Cardiac autoantibodies can complex. Most cases of myocarditis with onset in be demonstrated only later in the disease proc- otherwise healthy people probably have an infec- ess. A viral origin of myocarditis can only be tious origin, although the pathogenesis is not yet proved if the virus is detected within an altered fully understood (such as the finding of a link myocardium. This has become possible between chlamydia and heart disease through on September 24, 2021 by guest. Protected copyright. through molecular analyses of necropsy, trans- antigenic mimicry). In western countries entero- plant, and endomyocardial biopsy specimens viruses, especially coxsackie B 1–6 serotypes, are using new techniques of viral gene amplifica- the most frequent, and the recent identification tion, which have shown persistence of viral of a common coxsackie virus B and adenovirus mRNA.1 The histological diagnosis of myocar- receptor has explained why these very diVerent ditis (fig 1) was clarified by the Dallas criteria,7 virus types both cause myocarditis.2–4 but these unfortunately did not include immu- nohistochemistry to demonstrate a T cell mediated immune response. Prevalence and clinical features The prevalence of acute myocarditis is un- known because most cases are not recognised on account of non-specific or no symptoms (but sudden death may occur). Myocarditis may develop as a complication of an upper res- piratory or gastrointestinal infection with general constitutional symptoms, particularly fever and skeletal myalgia, malaise, and ano- rexia. This systemic acute phase response Correspondence to: increases energy production but compromises Professor Celia performance. Since myocarditis may not de- Oakley, Hammersmith velop for several days or weeks after the symp- Hospital, Du Cane toms and after a return to normal work and lei- Road, London Figure 1. Acute myocarditis showing sheets of pale W12 0HS, UK sure activity, there is a risk of overexertion, staining myocytes. Lymphocytes are seen which were [email protected] which may be dangerous. identified as CD4 and CD8 cells on immunohistology. www.heartjnl.com Education in Heart Myocardial failure in myocarditis Endocardial fibroelastosis in infancy and Contributory causes of myocardial dysfunction childhood, which was associated with persist- Heart: first published as 10.1136/heart.84.4.449 on 1 October 2000. Downloaded from include: ent mumps virus infection, has been almost (1) a direct cytotoxic eVect of the agent, be it eradicated by vaccination and the development viral, bacterial, etc; of vaccines against the other common viruses (2) a secondary immune response, which can may help reduce the incidence of myocarditis be triggered by any one of many diVerent in childhood. 450 agents including non-infective ones; (3) cytokine expression in the myocardium, which plays a crucial role—for example, Prognosis tumour necrosis factor á (TNF á) and Recovery from acute myocarditis often sur- nitric oxide synthase.4 prises and delights after life threatening illness. (4) aberrant induction of apoptosis, which Some recover seemingly normal ventricular may also play a part, particularly in function, but some cardiovascular reserve must individuals who go on to develop a chronic have been lost because biopsies during the cardiomyopathy.4 The proportion of pa- acute phase show myocytolysis. It is also tients who do this is completely unknown, uncertain how many will progress to dilated but a genetic predisposition to ongoing cardiomyopathy.13 inflammation, and possibly also to viral In a recent study 147 cases of myocarditis persistence, would explain the recognition were followed up for an average of 5.6 years. of a 25–30% familial incidence of dilated Out of 15 cases classed as fulminant, 93% were cardiomyopathy.8 alive without transplant 11 years after biopsy Detection of a causal agent is uncommon compared with 45% of 132 less severe cases. during the early phase (or even later). Demon- Left ventricular dilatation was not as great in stration of a viral origin is dependent upon the fulminant cases, who were more likely to gaining serial antibody titres against specific recover, as in the clinically milder cases who viruses and on showing a gradual fall in titre had bigger ventricles.14 during convalescence. Even if endomyocardial biopsy is carried out, persisting viral mRNA will be found in only 25–50% of patients with Other causes of acute myocarditis biopsy proven acute myocarditis.9 Lyme disease caused by Borrelia burgdorferi,a tick borne organism carried by deer, may cause an acute myocarditis, typically with a long PR Management interval as occurs with acute rheumatic fever. The treatment of acute myocarditis is largely Left ventricular dysfunction is usually transient supportive. EVective antiviral agents are but the organism has been cultured from unavailable and usually inappropriate, but they endomyocardial biopsy material in a patient http://heart.bmj.com/ need to be more extensively investigated for with a dilated cardiomyopathy. clinical use. Immunosuppressive agents would Chagas’ disease, common in rural parts of be inappropriate if the myocarditis were caused Central and South America, results from infec- by the direct eVect of persisting virus but tion by Trypanosoma cruzi. Although best potentially useful to suppress an ongoing known as a cause of heart block and cardio- autoimmune inflammatory response. Discour- myopathy in the chronic phase, it can also aging results were obtained in a randomised cause a severe acute myocarditis and sudden controlled trial of the use of immunosuppres- death. During this phase, but not the chronic sive agents in the treatment of biopsy proven one, trypanosomes can be shown lying within on September 24, 2021 by guest. Protected copyright. acute myocarditis.10 The trial was weakened by the myocytes. failure to include immunohistochemical tech- Kawasaki disease (Japanese mucocutaneous niques in the biopsy criteria and by frequent lymph node syndrome) can cause a diVuse protocol violations. The use of steroids in an myocarditis in its first or second stages. Occlu- acutely ill patient therefore remains a sion of proximal coronary artery aneurysms is discretionary clinical option in addition to the the usual cause of death. Treatment with use of diuretics, angiotensin converting enzyme immunoglobulins during the early phases may (ACE) inhibitors, â adrenergic blocking help to prevent aneurysms from forming. The agents, and spironolactone. cause is still unknown but is probably It is recommended that whenever myocardi- infective. tis is suspected exercise should be avoided.11 Peripartum cardiomyopathy (PPCM) is a Interestingly, in