1. MYOCARDITIS Dr. M. A. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin

2. Myocarditis World Health Organization/International Society and Federation Cardiology (WHO/ISFC) definition specifies diagnosis by established histological (Dallas criteria), immunological, and immunohistochemical criteria though many patients with clinical manifestations of myocarditis do not undergo endomyocardial biopsy so a definitive diagnosis is not established. Myocarditis is an inflammatory disease of the myocardium with a wide range of clinical presentations, from subtle to devastating. Clinical features of myocarditis: Myocarditis should be suspected in patients with or without cardiac signs and symptoms, who present with a rise in cardiac biomarker levels, change in electrocardiogram suggestive of acute myocardial injury, arrhythmia, or abnormalities of ventricular systolic function particularly if the these clinical findings are new and unexplained.

3. Chest pain: Mild symptoms of chest pain (in concurrent pericarditis), fever, sweats, chills, dyspnea. Myocarditis can mimic myocardial ischemia and/or infarction both symptomatically and on the electrocardiogram, particularly in younger patients In viral myocarditis: Recent history (≤1-2 wk) of flulike symptoms of fevers, arthralgias, and malaise or pharyngitis, tonsillitis, or upper respiratory tract infection Palpitations: A number of arrhythmias may be seen in patients with myocarditis. Sudden cardiac death: due to underlying ventricular arrhythmias or atrioventricular block (especially in giant cell myocarditis) Heart failure: Many symptomatic cases of postviral or lymphocytic myocarditis present with a syndrome of heart failure and dilated cardiomyopathy. Rapidly evolving diffuse, severe myocarditis can result in acute myocardial failure and cardiogenic shock. Signs and symptoms Myocarditis usually manifests in an otherwise healthy person and can result in rapidly progressive (and often fatal) heart failure and arrhythmia. Patients with myocarditis have a clinical history of acute decompensation of heart failure, but they have no other underlying cardiac dysfunction or have low cardiac risk

4. Excessive fatigue or exercise intolerance Partial or complete heart block, new-onset bundle branch block Chest pain New onset or worsening heart failure Unexplained sinus tachycardia Acute pericarditis S3, S4, or summation gallop Cardiogenic shock Abnormal electrocardiogram Sudden cardiac death Respiratory distress/tachypnea New cardiomegaly on chest x-ray Hepatomegaly Atrial or ventricular arrhythmia Partial or complete heart block, new-onset bundle branch block Clinical features of myocarditis

5. Diagnostic evaluation: The diagnostic evaluation of patients with suspected myocarditis should include the following components: History and physical examination Electrocardiogram (ECG) Cardiac biomarkers Chest radiograph. Natriuretic peptide measurement if the diagnosis of heart failure is uncertain. An echocardiogram is performed to evaluate regional and global ventricular function, valvular function, and other potential causes of cardiac dysfunction. Cardiovascular magnetic resonance (CMR) imaging may provide supportive evidence of myocarditis. In selected patients with suspected myocarditis, cardiac catheterization may aid determination of hemodynamic status. Coronary angiography is indicated in selected patients with clinical findings suggestive of acute coronary syndrome. Potential indications for endomyocardial biopsy (EMB) and other testing are reviewed.

6. Testing Laboratory studies use to evaluate suspected myocarditis may include the following: CBC ESR (and that of other acute phase reactants [eg, C-reactive protein] Rheumatologic screening Cardiac enzyme (eg, creatine kinase or cardiac troponins) Serum viral antibody titers Viral genome testing in endomyocardial biopsy Electrocardiography Imaging studies The following imaging studies may be used with suspected myocarditis: Echocardiography: To exclude other causes of heart failure (eg, amyloidosis or valvular or congenital causes) and to evaluate degree of cardiac dysfunction Antimyosin scintigraphy: To identify myocardial inflammation Cardiac angiography: To rule out IHD as cause of new-onset heart failure Gadolinium-enhanced MRI: To assess extent of inflammation and cellular edema; nonspecific Diagnostic work up

7. Sequential chest radiographs in myocarditis Posteroanterior view sequential chest radiographs in a young man with acute myocarditis (left) and three months later (right). Acutely, cardiomegaly and pulmonary congestion are apparent. Three months later, the lungs have cleared but the patient has developed dilated cardiomyopathy with persistent cardiomegaly.

8. Cardiovascular magnetic resonance images of coxsackievirus-induced myocarditis Cardiovascular magnetic resonance images of a 58- year-old woman with coxsackievirus- induced myocarditis and ventricular tachycardia. Late gadolinium enhancement is seen in a basal to mid anterior and anterolateral distribution (arrows). Note the epicardial to transmural distribution of the enhancement, which is more consistent with myocarditis than myocardial infarction.

9. Drugs ethanol, anthracyclines and some other forms of chemotherapy, and antipsychotics, e.g. clozapine, also some designer drugs such as mephedrone Physical agents Electric shock, hyperpyrexia, and radiation Heavy metals (copper or iron) Immunologic Allergic (acetazolamide amitriptyline) Rejection after a heart transplant Autoantigens (scleroderma, systemic lupus erythematosus, sarcoidosis, systemic vasculitis such as Churg- Strauss syndrome, and Wegener's granulomatosis, Kawasaki disease) Toxins (arsenic, toxic shock syndrome, carbon monoxide, or snake venom) Causes: A large number of causes of myocarditis have been identified, but often a cause cannot be found. Worldwide, however, the most common cause is Chagas' disease

10. Infection Viral (adenovirus, parvovirus B19, coxsackie virus, HIV, enterovirus, rubella virus, polio virus, cytomegalovirus, human herpesvirus 6 and possibly hepatitis C) Bacterial (Brucella, Corynebacterium diphtheriae, gonococcus, Haemophilus influenzae, Actinomyces, Tropheryma whipplei, Vibrio cholerae, Borrelia burgdorferi, leptospirosis, and Rickettsia) Fungal (Aspergillus) Parasitic (ascaris, Echinococcus granulosus, Paragonimus westermani, schistosoma, Taenia solium, Trichinella spiralis, visceral larva migrans, and Wuchereria bancrofti) Protozoan (Trypanosoma cruzicausing Chagas diseasea nd Toxoplasma gondii Bacterial myocarditis is rare in patients without immunodeficiency.

11. Specific findings in special cases are as follows: Sarcoid myocarditis: Lymphadenopathy, also with arrhythmias, sarcoid involvement in other organs (up to 70%) Acute rheumatic fever: Usually affects heart in 50-90%; associated signs, such as erythema marginatum, polyarthralgia, chorea, subcutaneous nodules (Jones criteria) Hypersensitive/eosinop hilic myocarditis: Pruritic maculopapular rash and history of using offending drug Giant cell myocarditis: Sustained ventricular tachycardia in rapidly progressive heart failure Peripartum cardiomyopathy - Heart failure developing in the last month of pregnancy or within 5 months following delivery Diagnosis: The diagnosis of acute myocarditis is usually presumptive. Because many cases of myocarditis are not clinically obvious, a high degree of suspicion is required. Patients with myocarditis usually present with signs and symptoms of acute decompensation of heart failure (eg, tachycardia, gallop, mitral regurgitation, edema) and, in those with concomitant pericarditis, with pericardial friction rub.

12. Procedures Endomyocardial biopsy is the standard tool for diagnosing myocarditis. However, the use of routine endomyocardial biopsy in establishing the diagnosis of myocarditis rarely is helpful clinically, since histologic diagnosis seldom has an impact on therapeutic strategies, unless giant cell myocarditis is suspected Management In improving cardiac hemodynamics in heart failure, as well as providing supportive therapy, with the hope of prolonging survival Pharmacotherapy Medications used in the management of myocarditis include the following: Vasodilators (eg, nitroglycerin, sodium nitroprusside) Angiotensin-converting enzyme inhibitors (eg, enalapril) Diuretics (eg, furosemide) Anticoagulation may be advisable as a preventive measure Antiarrhythmics can be used cautiously, although most antiarrhythmic drugs have negative inotropic effects that may aggravate heart failure Inotropic drugs (eg, dobutamine, milrinone) may be necessary for severe decompensation, although they are highly arrhythmogenic

13. Nonpharmacother apy Supportive care in patients with myocarditis includes the following: Hemodynamic and cardiac monitoring Administration of supplemental oxygen Fluid management Surgical option Surgical intervention in myocarditis may include the following: Temporary transvenous pacing for complete heart block Cardiac transplantation Extreme cases:  Ventricular assist device or percutaneous circulatory support  left ventricular assistive devices (LVADs) and extracorporeal membrane oxygenation