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Myocarditis and Pericarditis
Elias V. Haddad, M.D., FACC
Advances in Cardiovascular Care 2012
Kingston, Jamaica
December 7, 2012
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Financial Disclosures
No disclosures relevant to this presentation
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Learning Objectives
• Recognize the major etiologies, clinical manifestations and treatment modalities in myocarditis
• Discuss the role of endomyocardial biopsy (EMB) in the work-up of myocarditis
• Summarize a modern management strategy for acute and relapsing pericarditis
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Myocarditis
Pericarditis
Myopericarditis
Definition of Myocarditis
• “Inflammation of the myocardium”
• “An inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes”
• “Myocardial inflammation that leads to progressive heart failure and/or arrhythmia”
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…That is often under-diagnosed and under-treated
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A Simple Problem…
Etiologies of Myocarditis • Viral
– Enterovirus
– Adenovirus
– Coxsackievirus
– HCV
– HIV
– Parvovirus
– Rabies virus
– Yellow fever
• Bacterial
– Mycobacterial
– Streptococcal species (GAS)
– Mycoplasma pneumoniae
– Treponema pallidum
• Fungal
– Aspergillus
– Candida
– Coccidiodes
– Cryptococcus
– Histoplasma
– Mucormycosis
• Protozoal
– Trypanosoma cruzi (Chagas)
• Toxins
– Anthracyclines
– Cocaine
– Interleukin-2
• Hypersensitivity
– Sulfonamides
– Cephalosporins
– Diuretics
– Digoxin
– TCA
– Dobutamine
– Methyldopa
– Spironolactone
• Immunologic syndromes
– Churg-Strauss
– Inflammatory bowel disease
– Giant Cell myocarditis
– Diabetes mellitus
– Sarcoidosis
– Systemic lupus erythematosus
– Thyrotoxicosis
– Takayasu’s arteritis
– Wegener’s granulomatosis
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Etiologies of Myocarditis • Viral
– Enterovirus
– Adenovirus
– Coxsackievirus
– HCV
– HIV
– Smallpox Vaccination
• Bacterial
– Mycobacterial
– Streptococcal species
– Mycoplasma pneumoniae
– Treponema pallidum
• Fungal
– Aspergillus
– Candida
– Coccidiodes
– Cryptococcus
– Histoplasma
• Protozoal
– Trypanosoma cruzi (Chagas)
• Parasitic
– Schistosomiasis
– Larva migrans
• Toxins
– Anthracyclines
– Cocaine
– Interleukin-2
• Hypersensitivity
– Sulfonamides
– Cephalosporins
– Diuretics
– Digoxin
– TCA
– Dobutamine
• Immunologic syndromes
– Churg-Strauss
– Inflammatory bowel disease
– Giant Cell myocarditis
– Diabetes mellitus
– Sarcoidosis
– Systemic lupus erythematosus
– Thyrotoxicosis
– Takayasu’s arteritis/Kawasaki arteritis
– Wegener’s granulomatosis
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Etiologies of Myocarditis
Meta-analysis of 12 studies performing PCR on biopsy specimens (N=289)
– 11 of 12 studies found a significantly increased enterovirus RNA in cases vs controls
– Odds ratio of 4.4
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Baboonian Heart 2007
Etiologies of Myocarditis
• Multicenter study of 624 patients with biopsy-proven myocarditis
– 38% found to have viral genome (adenovirus, enterovirus, cytomegalovirus) in biopsy specimens
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Bowles JACC 2003
Etiologies of Myocarditis
• Department of Defense Smallpox Vaccination Clinical Evaluation Unit
– Increased incidence of myocarditis in 2002
– Incidence of 7.8/100,000
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Eckart JACC 2004
Clinical Presentation
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Asymptomatic Fulminant Chest Pain
Dyspnea
Diagnostic Evaluation
• EKG
– Normal
– Non-specific T-wave inversion
– Conduction abnormalities
– ST elevation mimicking acute MI
• Echo
– Useful to rule-out other causes of cardiomyopathy
– Evaluate LV function and chamber sizes
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Diagnostic Evaluation
• Use of Cardiac Biomarkers
– CK/CKMB have low predictive value
– Troponin T sensitivity 53%, specificity 94%, positive predictive value 93%
– Troponin I (Multicenter Myocarditis Treatment trial) positive predictive value 82%
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Smith Circulation 1997
Lauer JACC 1997
Diagnostic Evaluation
• Contrast enhanced cardiac MRI – Focal myocardial enhancement
(edema) and wall motion abnormalities strongly suggest myocarditis
– Mid-wall striated late gadolinium enhancement is associated with active myocarditis by the Dallas histopathologic criteria
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Role of Endomyocardial Biopsy
• ACC/AHA Guidelines for Heart Failure Management
– Class IIa recommendation for EMB- “Endomyocardial biopsy can be useful in patients presenting with HF when a specific diagnosis is suspected that would influence therapy
– Class III for routine use in evaluation
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Hunt et al JACC 2009
Role of Endomyocardial Biopsy
• Dallas Criteria-standardized histopathologic definition of myocarditis
• Only 10% of patients with idiopathic heart failure will have a positive biopsy by the Dallas Criteria
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Role of Endomyocardial Biopsy
• Indications for Endomyocardial Biopsy: – Subacute or acute onset HF refractory to management
– Development of significant arrhythmias (heart block and VT)
– HF with rash, fever, peripheral eosinophilia
– History of lupus, scleroderma, polyarteritis nodosum
– New-onset cardiomyopathy with known amyloidosis, sarcoidosis, hemachromatosis
– Suspicion for Giant Cell Myocarditis (young age, rapid progression, progressive arrhythmias)
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Wu Mayo Clin Proc 2001
Role of Endomyocardial Biopsy • Histopathology can
predict transplant-free survival
– Lymphocytic, granulomatous and giant cell myocarditis on EMB predicted death or transplant
– Clinical variables (except PCWP >15) did not predict the primary end-point
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Magnani Am Heart J 2006 Kindermann Circulation 2008
Treatment Modalities
• Supportive Care
• Supportive Care
•Supportive Care
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Hemodynamic Support Modalities
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Treatment Modalities
• After initial hemodynamic stabilization
– ACC/AHA guidelines for pharmacologic intervention in heart failure
• ϐ-adrenergic blockade
• ACE inhibitors/ARB
• Aldosterone antagonists (spironolactone, eplerenone)
• Decision to implant an ICD should be deferred for several months if possible
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Treatment Modalities
• Immunosuppression
– Myocarditis Treatment Trial*
• 111 patients
• Randomized to placebo or immunosuppression
• No difference in mortality or LVEF at 28 weeks
*Immunosuppression may be of benefit in patients with myocarditis in the setting of systemic autoimmune diseases
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*Mason NEJM 1995
Acute Pericarditis
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Myocarditis
Pericarditis
Myopericarditis
A Simple Problem with a Simple Solution?
The Problem
• Inflammation
• Fluid
• Constriction
The Solution
• Reduce Inflammation
• Drain the fluid
• Remove the pericardium
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Adapted from Nishimura RA, Pericardial Disease 2011
…That is often undertreated and mismanaged
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A Simple Problem…
Pericardial Disease
A 39 year old man presents with three days of severe chest pain that is pleuritic in nature. Improved by sitting up. He had an upper respiratory infection for the last week.
Exam: HR 92 BP 120/77
JVP < 8 cm H20, brisk carotid upstrokes
Normal heart sounds, no murmur
Three-part friction rub heard at LLSB
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Pericardial Disease
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Diffuse ST-elevation
PR depression
Other tests are optional unless…
• Heart failure signs/symptoms—Echo
• Pulses paradoxus—Echo
• High-risk for CAD—Cardiac biomarkers
• Recurrent pericarditis—Autoimmune profile
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Treatment
• DO USE NSAIDs or high-dose aspirin for one month, then taper slowly (can follow ESR)
• DO GIVE cochicine for the first 6 months to reduce risk of relapse
• DO NOT use steroids due to increased risk of relapsing pericarditis
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Relapsing Pericaritis
• Usually due to use of steroids with rapid taper
• Management:
– High-dose aspirin with goal salicylate level 10-20
– VERY SLOW steroid taper, 1 mg per month
– Colchicine
– In refractory cases, consider pericardiectomy
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Take-Home Points
• Myocarditis and Pericarditis are overlapping conditions sharing a number of characteristics
• Treatment of myocarditis remains supportive care with good heart failure management
• Use of steroids in pericarditis increases the risk of relapsing disease
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