1. Viral Myocarditis and Dilated Cardiomyopathy Kristine Scruggs, MD AM Report 10 March 2010 EdEd

2. Signs & Symptoms of Myocarditis Excessive fatigue Chest pain Unexplained sinus tachycardia Acute pericarditis S3, S4 or summation gallop Abnormal electrocardiogram Abnormal echocardiogram New cardiomegaly on CXR Atrial or ventricular arrhythmia Partial or complete heart block New onset CHF Atypical MI Cardiogenic shock Sudden, unexpected death

3. Etiologies of DCM (Felker, et al.) Idiopathic (50%) Myocarditis (9%) – Viral, Bacterial, Fungal, Protozoal, Helminth Ischemic heart disease (7%) Infiltrative disease (5%) – Amyloidosis, Sarcoidosis, Hemochromatosis Peripartum cardiomyopathy (4%) Hypertension (4%) HIV infection (4%) Connective Tissue Disease(3%) – Scleroderma, SLE, etc Substance abuse (3%) – Cocaine, EtOH Doxorubicin (1%) Other (10%) – Restrictive CM, Familial CM, Valvular heart dz, Endocrine, Neuromuscular, Neoplastic, Drugs (other), Critical illness, etc.

4. Viral Etiologies of Myocarditis Enterovirus (e.g. Coxsackie B)* Adenovirus* Hepatitis C CMV Echovirus Influenza EBV Parvovirus B-19 HHV-6 *Associated with progression to DCM (Bowles, et al.)

5. Diagnosis Serologies Cultures PCR (direct examination of cardiac tissue) Incidence/prevalence of viral myocarditis difficult to assess – No non-invasive “gold standard” – 3.5-5% cardiac involvement during coxsackie outbreak – 6% at autopsy of SCD in young athletes 149 pts w/ DCM unknown etiology, + PCR in 20% (Bowles, et al) – Versus 1.4% in controls – All adenovirus (60%) and enterovirus (40%) 1230 pts w/ DCM, mycarditis the cause in 9% (Felker, et al.)

7. Pathophysiology of Viral Myocarditis --> DCM Late sequela of acute or chronic viral myocarditis Due to – direct viral injury (viral toxicity, perforin-mediated cell lysis, cytokine expression) – persistence of virus (initial immune response is protective) – autoimmune phenomenon (“anti-heart” antibodies) In one study, 93% of patients with myocarditis on biopsy had history of preceding viral illness (Bowles, et al.) Initial immune response is probably protective – Decreases inflammation – Stronger humoral and cellular immune response linked to less severe initial disease

8. Take Home Points Viral infection (esp. with adeno, entero) causes myocarditis in up to 5% of cases In patients with newly diagnosed DCM, 9% have been traced to viral myocarditis Incidence/prevalence is difficult to assess as there is no “gold standard” for diagnosis Damage is caused by direct viral injury, persistent viral infection/inflammation, and auto-immune phenomena. Prognosis is thought to be generally good, as only the severe cases present with clinical findings – Recent onset IDCM (<6 mo) showed improvement from baseline EF 25% to 42% in one year – Transplant free survival 92% at one year and 88% at two years (McNamara, et al.)

9. Questions?

10. References Bowles NE, et al. Detection of Viruses in Myocardial Tissues by Polymerase Chain Reaction: Evidence of Adenovirus as a Common Cause of Myocarditis in Children and Adults. J Am Coll of Card. 2003. 42: 3. 466-472. Cooper LT, et al. Etiology and Pathogenesis of Myocarditis. UpToDate. 2009. Felker GM, et al. Underlying Causes and Long-term Survival in Patients with Initially Unexplained Cardiomyopathy. New Engl J of Med. 2000. 342: 15. 1077-1081. McNamara DM, et al. Controlled Trial of Intravenous Immune Globulin in Recent-Onset Dilated Cardiomyopathy. Circulation. 2001; 103:2254-2259.