1. Apr 19, 2012 內科 & ER Combined Conference

2. Outline The differential diagnosis of non- coronary chest pain with elevated cardiac isoenzyme. The differential diagnosis of non- coronary chest pain with elevated cardiac isoenzyme. How to diagnose and treat myocarditis? How to diagnose and treat myocarditis?

3. Noncoronary Chest Pain and Elevated Cardiac Isoenzyme Myocarditis Myocarditis Takotsubo cardiomyopathy Takotsubo cardiomyopathy Cardiac emboli Cardiac emboli Atrial fibrillation Atrial fibrillation Patent foramen ovale Patent foramen ovale Infective endocarditis Infective endocarditis Dilated cardiomyopathy Dilated cardiomyopathy Shock Shock

4. Takotsubo Cardiomyopathy Broken heart syndrome, apical ballooning syndrome Broken heart syndrome, apical ballooning syndrome Triggered by emotional stress Triggered by emotional stress EKG changes suggestive of AMI, ant. EKG changes suggestive of AMI, ant. Mild elevated cardiac isoenzyme Mild elevated cardiac isoenzyme Female Female

5. New-Onset Chest Pain, Elevated Troponin and Nonobstructed CAD Eur Heart J 2007; 28:1242–9 CMR findingsN (%) Myocarditis30 (50) Acute19 (31.7) Chronic11 (18.3) Myocardial infarction7 (11.6) Takotsubo cardiomyopathy1 (1.7) Dilated cardiomyopathy1 (1.7) Normal CMR findings21 (35) 60 patients CMR within 3 months of initial presentation

6. How to Diagnose Myocarditis?

7. Clinical Presentation Acute Heart Failure -with dilated CMP, within 2 wks of viral syndrome Acute Heart Failure -with dilated CMP, within 2 wks of viral syndrome Sudden Loss of Consciousness - poor prognosis if ventricular tachycardia or heart block Sudden Loss of Consciousness - poor prognosis if ventricular tachycardia or heart block Chest Pain - with myopericardits Chest Pain - with myopericardits

8. No Sensitive or Specific Test for Myocarditis NoSensitivitySpecificity Positive Predictive Negative predictive Troponin T8053%96%93%56% Troponin I8834%89%?? JACC 2006; 48:2085

10. Dallas Criteria for Myocarditis Active myocarditis Active myocarditis inflammatory infiltrate of myocardium with necrosis of myocytes not typical of CAD. inflammatory infiltrate of myocardium with necrosis of myocytes not typical of CAD. Borderline myocarditis Borderline myocarditis inflammatory infiltrate of myocardium without necrosis of myocytes. inflammatory infiltrate of myocardium without necrosis of myocytes.

11. Expanded Criteria for Diagnosis of Myocarditis Clinical symptoms Clinical symptoms Evidence of cardiac structural or functional perturbation in the absence of regional coronary ischemia Evidence of cardiac structural or functional perturbation in the absence of regional coronary ischemia Cardiac MRI Cardiac MRI Myocardial biopsy— pathologic or molecular analysis Myocardial biopsy— pathologic or molecular analysis 2: suggestive, 3: compatible, 4: high probability

12. Many Injury Can Cause Myocarditis Viruses: changing spectrum Viruses: changing spectrum Toxin: chemotherapy Toxin: chemotherapy Radiation Radiation Allergic Reaction Allergic Reaction Bacteria, Fungal, Protozoal Infections Bacteria, Fungal, Protozoal Infections Genetic Predisposition Genetic Predisposition

13. Etiology Viral (Most Common) Viral (Most Common) Adenovirus Adenovirus Coxsackievirus, enterovirus Coxsackievirus, enterovirus Cytomegalovirus Cytomegalovirus Parvovirus B19 Parvovirus B19 Hepatitis C virus Hepatitis C virus Influenza virus Influenza virus Dengue virus Dengue virus Herpes virus Herpes virus Mixed infections Mixed infections

14. Acute Myocarditis Viral prodrome (20- 80%) Viral prodrome (20- 80%) Fever, chills, myalgia Fever, chills, myalgia Common symptoms Common symptoms Fatigue (82%) Fatigue (82%) DOE (81%) DOE (81%) Arrhythmias (55%) Arrhythmias (55%) Palpitation (49%) Palpitation (49%) Chest pain at rest (26%) Chest pain at rest (26%) Elevated troponin Elevated troponin ST segment elevation, depression, T inversion ST segment elevation, depression, T inversion Segmental wall motion abnormality by echo Segmental wall motion abnormality by echo

15. Fulminant Myocarditis 10% biopsy proven myocarditis 10% biopsy proven myocarditis Abrupt, within 2 wks of viral illness Abrupt, within 2 wks of viral illness Hemodynamic compromise and hypotension Hemodynamic compromise and hypotension Diffuse global hypokinesia, rarely dilated ventricle, thick ventricular walls Diffuse global hypokinesia, rarely dilated ventricle, thick ventricular walls Better prognosis compared with chronic myocarditis Better prognosis compared with chronic myocarditis

16. Diagnostic Efficacy for Myocarditis Sensitivity (%)Specificity (%) EKG changes47? Troponin > 0.1ng/mL34-5389-94 CPK – MB form6? Antibody to virus or myosin25-3240 Indium 111 antimyosin scintigraphy 85-9134-53 Echo (ventricular dysfunction)69? Cardiac MRI8695 Myocardial biopsy (pathology)35-5078-89 Myocardial biopsy (viral genome by PCR) 38-6580-100 ? Indeterminate or poor

17. Gadolinium-enhancedT2-weighted inflammation Persistent fibrosis Eur Heart J 2007; 28:1242–9

18. Cine sequenceLGE Transmural T2-weighted Myocarditis LGE Patchy epicardial Eur Heart J 2007; 28:1242–9 CAD

19. How to Treat Myocarditis?

21. Thank you

22. Pathophysiologic Stages