Myocarditis

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  • Myocarditis

    1. 1. Young Soldier With A Failing Heart Manju Goyal, M.D. Walter Reed Army Medical Center April 2008
    2. 2. Case <ul><li>HPI: 20 year-old male with cough, shortness of breath, intermittent chest pressure and palpitations x 4 days </li></ul><ul><li>PMhx/PSHx/Shx/Fhx/Meds: negative </li></ul><ul><li>EXAM: </li></ul><ul><li>Vitals: 145, 90/58, 95% ra, afebrile </li></ul><ul><li>Cardiovascular: tachycardic, systolic murmur best heard at the apex, no JVD </li></ul><ul><li>Lungs: CTAB </li></ul><ul><li>Extremities: no edema </li></ul>
    3. 3. Case <ul><li>LABS: </li></ul><ul><li>CBC - nml </li></ul><ul><li>BMP - nml </li></ul><ul><li>D-dimer - nml </li></ul><ul><li>BNP - 397 </li></ul><ul><li>LFTs - 88/136 </li></ul><ul><li>Cardiac enzymes - 115/2.2/<0.01 </li></ul>
    4. 4. Case <ul><li>EKG – sinus tachycardia at 131, inferolateral TWI </li></ul><ul><li>CXR – AP film with just an enlarged cardiac silhouette </li></ul>Young patient in SHOCK with concerning cardiac exam and EKG
    5. 5. Case <ul><li>ECHO: </li></ul><ul><li>Severely dilated left ventricle but normal wall thickness </li></ul><ul><li>No LV thrombus </li></ul><ul><li>EF in the 10-15% range </li></ul><ul><li>Severe global hypokinesis, with mild posterior wall contractility. </li></ul><ul><li>Moderate to severe MR due to annular dilatation </li></ul>New onset of Dilated Cardiomyopathy (DCM)
    6. 6. Dilated Cardiomyopathy www.uptodate.com
    7. 7. Review of 1230 Patients with DCM <ul><li>Idiopathic — 50 percent </li></ul><ul><li>Myocarditis — 9 percent </li></ul><ul><li>Ischemic heart disease — 7 percent </li></ul><ul><li>Infiltrative disease — 5 percent </li></ul><ul><li>Peripartum cardiomyopathy — 4 percent </li></ul><ul><li>Hypertension — 4 percent </li></ul><ul><li>HIV infection — 4 percent </li></ul><ul><li>Connective tissue disease — 3 percent </li></ul><ul><li>Substance abuse — 3 percent </li></ul><ul><li>Doxorubicin — 1 percent </li></ul><ul><li>Other — 10 percent </li></ul>NEJM 2000
    8. 8. Importance of Etiology NEJM 2000
    9. 9. Additional Tests <ul><li>LABS: </li></ul><ul><li>ESR - 33 </li></ul><ul><li>Ferritin - nml </li></ul><ul><li>TSH - nml </li></ul><ul><li>ACE level - nml </li></ul><ul><li>RF - nml </li></ul><ul><li>ANA - negative </li></ul><ul><li>Lyme titers - negative </li></ul><ul><li>HIV - negative </li></ul><ul><li>Cardiac CATH: </li></ul><ul><li>Normal Coronaries </li></ul>What’s the differential? Any further tests?
    10. 10. Review of 1230 Patients with DCM <ul><li>Idiopathic — 50 percent </li></ul><ul><li>Myocarditis — 9 percent </li></ul><ul><li>Ischemic heart disease — 7 percent </li></ul><ul><li>Infiltrative disease — 5 percent </li></ul><ul><li>Peripartum cardiomyopathy — 4 percent </li></ul><ul><li>Hypertension — 4 percent </li></ul><ul><li>HIV infection — 4 percent </li></ul><ul><li>Connective tissue disease — 3 percent </li></ul><ul><li>Substance abuse — 3 percent </li></ul><ul><li>Doxorubicin — 1 percent </li></ul><ul><li>Other — 10 percent </li></ul>NEJM 2000 Endomyocardial Biopsy
    11. 11. Biopsy Results Dr. Brendan Graham Dept. of Pathology
    12. 12. Normal Myocardium
    13. 13. Biopsy – 4x
    14. 14. Biopsy – 20x
    15. 15. Biopsy – 40x
    16. 16. Case of Viral Myocarditis <ul><li>Other infectious etiologies ruled out by special stains/cultures </li></ul><ul><li>Dallas Criteria: </li></ul><ul><ul><li>Lymphocytic infiltrates of varying severity </li></ul></ul><ul><ul><li>Myocyte necrosis and cytoskeletal disorganization </li></ul></ul><ul><li>Interstitial fibrosis seen with subacute/chronic cases </li></ul>
    17. 17. Objectives: Myocarditis <ul><li>Review etiology and pathophysiology </li></ul><ul><li>Clinical Manifestations </li></ul><ul><li>Role of different diagnostic modalities </li></ul><ul><li>Therapy </li></ul><ul><ul><li>Cardiovascular support for an unstable patient (i.e. indications for VAD, ECMO) </li></ul></ul><ul><ul><li>Role of immunosuppressive/modulating therapies </li></ul></ul><ul><li>Prognosis </li></ul>
    18. 18. Myocarditis <ul><li>Definition: </li></ul><ul><li>Non-ischemic myocardial inflammation resulting from a variety of infectious, immune and toxic insults. </li></ul>
    19. 19. Epidemiology <ul><li>Precise incidence and prevalence unknown </li></ul><ul><li>Lack of a non-invasive “gold standard” test for diagnosis </li></ul><ul><ul><li>Not every suspected myocarditis case gets a biopsy </li></ul></ul><ul><ul><li>Biopsy itself has low sensitivity </li></ul></ul><ul><li>Present in 1-9% of routine postmortem examinations 1 </li></ul><ul><li>Accounted for 20% of sudden cardiac deaths in military recruits 2 </li></ul>1. Circulation 1976 2. Ann Intern Med 2004
    20. 20. Etiology <ul><li>Infectious </li></ul><ul><li>VIRUSES (adeno, coxsackie) </li></ul><ul><li>Bacterial </li></ul><ul><li>Fungal </li></ul><ul><li>Protozoal (Chagas disease) </li></ul><ul><li>Helminths </li></ul><ul><li>Non-infectious </li></ul><ul><li>Toxins/Drugs (alcohol, anthracyclines) </li></ul><ul><li>Systemic disorders (sarcoid, lupus, scleroderma) </li></ul>
    21. 21. Etiology
    22. 22. Etiology Braunwald 2007
    23. 23. Pathophysiology of Viral Myocarditis Braunwald 2007
    24. 24. Viral Phase <ul><li>Virus enters (GI/Lungs) </li></ul><ul><li>Activates proteases  damages cytoskeletan </li></ul><ul><li>Activates tyrosine kinases  immune system turns ON </li></ul><ul><li>Replicates and persists  chronic inflammation/fibrosis/DCM </li></ul>Braunwald 2007
    25. 25. Immune Response Braunwald 2007 Autoimmune response : auto-antibodies to myosin and other cardiac proteins Overexpression of cytokines (IL-2, INF- γ , TNF- α )
    26. 26. Pathophysiology
    27. 27. Clinical Presentation Acute Fulminant Chronic <ul><li>Nonspecific cardiac symptoms </li></ul><ul><li>Heart failure, Acute MI, or SCD </li></ul><ul><li>More common in children/teenagers </li></ul><ul><li>+/- viral prodrome </li></ul><ul><li>Cardiogenic shock +/- acute heart failure </li></ul><ul><li>Biopsy doesn’t match the clinical severity. </li></ul><ul><li>High levels of cytokines  reversible cardiac depression  better prognosis </li></ul><ul><li>Subtle, insidious onset </li></ul><ul><li>Already have DCM  HF symptoms </li></ul><ul><li>Biopsy with fibrosis usually </li></ul>
    28. 28. Diagnosis <ul><li>Symptoms: non-specific </li></ul><ul><li>Laboratory Testing: also non-specific </li></ul><ul><ul><li>Positive cardiac biomarkers </li></ul></ul><ul><ul><li>ECG: T wave inversion, ST segment elevation, bundle branch blocks </li></ul></ul><ul><li>ECHO </li></ul><ul><ul><li>Differentiate fulminant from acute myocarditis </li></ul></ul><ul><ul><li>Detect thrombi, valvular abnormalities, and pericardial involvement </li></ul></ul><ul><ul><li>Rule out other cardiomyopathies (HOCM, Takotsubo) </li></ul></ul>
    29. 29. Diagnosis: Cardiac MRI <ul><li>Non-invasive </li></ul><ul><li>Visualize entire myocardium </li></ul><ul><li>Use to guide biopsy </li></ul><ul><li>Follow disease course and response to therapy </li></ul>WITH Contrast WITHOUT Contrast Eur Heart J 1994 LV RV RV LV
    30. 30. Diagnosis: Coronary Angiography <ul><li>Rule out other congenital, rheumatic, or ischemic heart disease </li></ul><ul><li>Determine need for inotropic or mechanical support based on hemodynamic parameters </li></ul><ul><li>Elevated pulmonary artery pressures are independent predictors of mortality </li></ul>
    31. 31. Diagnosis: Endomyocardial Biopsy <ul><li>Although controversial, still the current gold-standard test for diagnosis </li></ul><ul><li>1-6% complication rate </li></ul><ul><li>Consider when suspicious for: </li></ul><ul><ul><li>Giant cell myocarditis </li></ul></ul><ul><ul><li>Hypersensitivity/eosinophilic myocarditis </li></ul></ul><ul><ul><li>Cardiac involvement in a systemic disease </li></ul></ul><ul><li>All other patients, consider only if pt is deteriorating </li></ul>
    32. 32. When to consider biopsy? Mayo Clin Proc 2001
    33. 33. Circulation 2007
    34. 34. Treatment Dr. Barnett Gibbs Dept. of Cardiology
    35. 35. Treatment
    36. 36. Treatment
    37. 37. Treatment <ul><li>ABC’s </li></ul><ul><li>Circulation: </li></ul><ul><ul><ul><li>Intra-aortic balloon pump counterpulsation </li></ul></ul></ul><ul><ul><ul><li>Ventricular assist device </li></ul></ul></ul><ul><ul><ul><li>Cardiopulmonary assist device </li></ul></ul></ul>
    38. 38. Intra-aortic balloon pump <ul><li>Electrocardiographic synchronized phased pulsation </li></ul><ul><ul><li>Inflation with aortic valve closure </li></ul></ul><ul><ul><li>Deflation just before systole </li></ul></ul><ul><li>Reduce systolic arterial pressure (afterload) </li></ul><ul><ul><li>Reduces myocardial oxygen consumption </li></ul></ul><ul><li>Augment diastolic arterial pressure </li></ul><ul><ul><li>Enhances coronary blood flow </li></ul></ul><ul><li>Mean pressure unchanged </li></ul>
    39. 39. Intra-aortic balloon pump <ul><li>Benefits: </li></ul><ul><ul><li>Diminish myocardial ischemia </li></ul></ul><ul><ul><li>10-20% increase in CO </li></ul></ul><ul><ul><li>Diminish heart rate </li></ul></ul><ul><ul><li>Increase urine output </li></ul></ul><ul><li>Risks: </li></ul><ul><ul><li>Damage/perforation of aorta </li></ul></ul><ul><ul><li>Distal ischemia </li></ul></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><ul><li>Hemolysis </li></ul></ul><ul><ul><li>Renal emboli </li></ul></ul><ul><ul><li>Mechanical failure – balloon rupture </li></ul></ul>
    40. 40. Ventricular-assist device <ul><li>Centrifugal pump or Archimedes’ screw type </li></ul><ul><li>Inflow from LV and outflow into aorta </li></ul><ul><li>Has been used as a bridge in myocarditis until recovery or transplant </li></ul>
    41. 41. * *Centrifugal pump vs. corkscrew
    42. 42. Ventricular-assist device <ul><li>Centrifugal pump or Archimedes’ screw type </li></ul><ul><li>Inflow from LV and outflow into aorta </li></ul><ul><li>Has been used as a bridge in myocarditis until recovery or transplant </li></ul><ul><ul><li>Disadvantages: </li></ul></ul><ul><ul><ul><li>Surgical implantation </li></ul></ul></ul><ul><ul><ul><li>infection </li></ul></ul></ul><ul><ul><ul><li>thrombosis </li></ul></ul></ul><ul><ul><ul><li>hemolysis </li></ul></ul></ul>
    43. 43. Ventricular-assist device <ul><li>Infection: </li></ul><ul><ul><li>Review of 76 patients using LVAD to bridge to cardiac transplant </li></ul></ul><ul><ul><li>LVAD-related infection: </li></ul></ul><ul><ul><ul><li>38 patients (50%) </li></ul></ul></ul><ul><ul><ul><li>29 bloodstream infections (including 5 cases of endocarditis) </li></ul></ul></ul><ul><ul><ul><li>17 local infections </li></ul></ul></ul>CID. 2005;40:1108.
    44. 44. Treatment
    45. 45. Treatment <ul><li>ABC’s </li></ul><ul><li>Circulation: </li></ul><ul><ul><ul><li>Intra-aortic balloon pump counterpulsation </li></ul></ul></ul><ul><ul><ul><li>Ventricular assist device </li></ul></ul></ul><ul><ul><ul><li>Cardiopulmonary assist device </li></ul></ul></ul><ul><ul><li>Medical therapy </li></ul></ul><ul><ul><ul><li>ACE-inhibitors </li></ul></ul></ul><ul><ul><ul><li>Beta-blockers </li></ul></ul></ul>
    46. 46. Medical therapy <ul><li>Most therapy used in HF patients appears to benefit those with HF due to myocarditis – with the exception of digoxin </li></ul><ul><ul><li>ACE-inhibitors </li></ul></ul><ul><ul><li>Beta-blockers </li></ul></ul><ul><ul><li>No RCT reviewing spironolactone or ARBs but these as well as other HF meds have been used successfully in case reports </li></ul></ul>
    47. 47. Medical therapy <ul><li>Animal models appear to demonstrate improved function with use of ACE inhibitors </li></ul><ul><ul><li>32 mice infected with Coxsakie B3 virus </li></ul></ul><ul><ul><li>Randomized to captopril vs. placebo on day 3 </li></ul></ul><ul><ul><li>This evidence has been extrapolated to humans </li></ul></ul>Am Heart J. 1990;120:1377.
    48. 48. Medical therapy <ul><li>Animal models appear to demonstrate improved function with use of beta-blockers </li></ul>Circulation. 1991;83:2021..
    49. 49. Treatment
    50. 50. Treatment <ul><li>ABC’s </li></ul><ul><li>Circulation: </li></ul><ul><ul><ul><li>Intra-aortic balloon pump counterpulsation </li></ul></ul></ul><ul><ul><ul><li>Ventricular assist device </li></ul></ul></ul><ul><ul><ul><li>Cardiopulmonary assist device </li></ul></ul></ul><ul><ul><li>Medical therapy </li></ul></ul><ul><ul><ul><li>ACE-inhibitors </li></ul></ul></ul><ul><ul><ul><li>Beta-blockers </li></ul></ul></ul><ul><ul><li>Immunosuppressive therapy </li></ul></ul>
    51. 51. Immunosuppressive Therapies <ul><li>Recent meta-analysis of placebo-controlled RCT of immune therapy for myocarditis </li></ul><ul><ul><li>Five trials; 316 total patients </li></ul></ul><ul><ul><li>Single or combination immunosuppressive therapy </li></ul></ul><ul><ul><ul><li>Prednisone </li></ul></ul></ul><ul><ul><ul><li>Azathioprine </li></ul></ul></ul><ul><ul><ul><li>Cyclosporine </li></ul></ul></ul><ul><ul><ul><li>IVIG </li></ul></ul></ul>Int Heart J. 2005;46:113.
    52. 52. Immunosuppressive Therapies Int Heart J. 2005;46:113.
    53. 53. Immunosuppressive Therapies <ul><li>End-points: </li></ul><ul><ul><li>All cause death </li></ul></ul><ul><ul><li>Heart transplantation </li></ul></ul><ul><ul><li>Secondary: </li></ul></ul><ul><ul><ul><li>Change in LVEF and LVEDD </li></ul></ul></ul><ul><li>Summary: </li></ul><ul><ul><li>No statistically significant benefit in treatment of myocarditis with immunosuppressive therapy </li></ul></ul>Int Heart J. 2005;46:113. NEJM. 2000;343:1388.
    54. 54. Prognosis <ul><li>Review of 1230 patients with cardiomyopathy </li></ul><ul><ul><li>Idiopathic cardiomyopathy (n=616 patients) </li></ul></ul><ul><ul><li>Peripartum cardiomyopathy (51) </li></ul></ul><ul><ul><li>Myocarditis (111) </li></ul></ul><ul><ul><li>Ischemic heart disease (91) </li></ul></ul><ul><ul><li>Infiltrative myocardial disease (59) </li></ul></ul><ul><ul><li>Hypertension (49) </li></ul></ul><ul><ul><li>Human immunodeficiency virus (45) </li></ul></ul><ul><ul><li>Connective-tissue disease (39) </li></ul></ul><ul><ul><li>Substance abuse (37) </li></ul></ul><ul><ul><li>Therapy with doxorubicin (15) </li></ul></ul><ul><ul><li>Other causes (117) </li></ul></ul>NEJM. 2000;342:1077.
    55. 55. Prognosis <ul><li>Idiopathic CM acted as the reference category </li></ul><ul><li>No difference in survival between idiopathic CM and cardiomyopathy due to myocarditis </li></ul>NEJM. 2000;342:1077.
    56. 56. Prognosis NEJM. 2000;342:1077.
    57. 57. Prognosis <ul><li>“Loose” rule of third’s… </li></ul><ul><ul><li>1/3: recover </li></ul></ul><ul><ul><li>1/3: residual ventricular dysfunction </li></ul></ul><ul><ul><li>1/3: transplantation or death </li></ul></ul>
    58. 58. SUMMARY <ul><li>ABC’s </li></ul><ul><li>Supportive therapy is mainstay therapy </li></ul><ul><li>Most medical therapies for HF seem to benefit myocarditis patients with the exception of digoxin </li></ul><ul><li>Immunosuppressive therapy does not seem to play a role in survival </li></ul>
    59. 59. Back to the case <ul><li>Stabilized initially with LVAD and ECMO </li></ul><ul><li>EF increased to 40-45% </li></ul><ul><li>Started on coreg, lisinopril, and aldactone </li></ul><ul><li>Multiple complications during the hospital course </li></ul><ul><ul><li>Cardiac tamponade s/p thoracotomy </li></ul></ul><ul><ul><li>Hemorrhagic CVA s/p craniotomy, tracheostomy and a PEG </li></ul></ul><ul><ul><li>Multiple Infections </li></ul></ul><ul><li>Currently, at a rehab facility due to residual neurologic deficit and deconditioning </li></ul>
    60. 60. Conclusion <ul><li>Most common cause is viruses (adeno and coxsackie) </li></ul><ul><li>Highly variable clinical manifestations </li></ul><ul><li>Cardiac MRI looks promising for diagnosis </li></ul><ul><li>Biopsy is the gold standard but should be pursued in only select patients </li></ul><ul><li>Aggressive, supportive care is the first line therapy because of high incidence of recovery </li></ul><ul><li>Immunosuppressive therapy does not affect mortality </li></ul>
    61. 61. References <ul><li>Felker GM et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000 Apr; 342(15): 1077-84. </li></ul><ul><li>Cooper LT et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease. Circulation 2007 Nov; 116: 2216-2233. </li></ul><ul><li>www.uptodate.com </li></ul><ul><li>Baughman KL:  Diagnosis of myocarditis: Death of Dallas criteria.   Circulation    2006; 113:593. </li></ul><ul><li>Wu LA et al. Current role of endomyocardial biopsy in the management of patients with dilated cardiomyopathy and myocarditis. Mayo Clin Proc 2001; 76:1030 </li></ul><ul><li>Cooper LT et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 2007; 116: 2216 </li></ul><ul><li>Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed. </li></ul><ul><li>Goldberg LR et al. Predictors of adverse outcome in biopsy-proven myocarditis. JACC 1999; 33 </li></ul><ul><li>Eckart RE, Scoville SL, Campbell CL, et al. Sudden death in young adults: a 25-year review of autopsies in military recruits. Ann Intern Med . 2004;141:829–834. </li></ul><ul><li>Blankenhorn MA, Gall EA. Myocarditis and myocardosis; a clinicopathologic appraisal. Circulation . 1956;13:217–223. </li></ul><ul><li>Kuhl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation . 2005;112:1965–1970. </li></ul><ul><li>Fuse K, Kodama M, Okura Y, et al. Predictors of disease course in patients with acute myocarditis. Circulation . 2000;102:2829 –2835. </li></ul><ul><li>Ellis CR, et al. Myocarditis basic and clinical aspects. Cardiology in Review 2007;15: 170–177 </li></ul>
    62. 62. Biopsy <ul><li>2-5% complication rate </li></ul><ul><ul><li>Venous access : inadvertent arterial puncture, pneumothorax, vasovagal reaction, or bleeding after sheath removal </li></ul></ul><ul><ul><li>Procedure itself : arrhythmias, conduction abnormalities, and cardiac perforation  to pericardial tamponade and rarely, death. </li></ul></ul><ul><li>Patchy infiltrates  lower sensitivity </li></ul><ul><li>Lateral wall most common  hard to access </li></ul>
    63. 63. Diagnosis <ul><li>Expanded Criteria </li></ul><ul><ul><li>Suspicious for myocarditis = 2 positive categories </li></ul></ul><ul><ul><li>Compatible with myocarditis = 3 positive categories </li></ul></ul><ul><ul><li>High probability of being myocarditis = all 4 categories positive </li></ul></ul><ul><li>Category I : Clinical symptoms </li></ul><ul><li>Category II : Evidence of Cardiac dysfunction in the Absence of regional coronary ischemia </li></ul><ul><li>Category III : Cardiac MRI </li></ul><ul><li>Category IV : Myocardial biopsy - Pathological or Molecular Analysis </li></ul>

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