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Young Soldier With A
Failing Heart
Manju Goyal, M.D.
Walter Reed Army Medical Center
April 2008
Case
HPI: 20 year-old male with cough, shortness of breath,
intermittent chest pressure and palpitations x 4 days
PMhx/PSHx/Shx/Fhx/Meds: negative
EXAM:
Vitals: 145, 90/58, 95% ra, afebrile
Cardiovascular: tachycardic, systolic murmur best heard at
the apex, no JVD
Lungs: CTAB
Extremities: no edema
Case
LABS:
CBC - nml
BMP - nml
D-dimer - nml
BNP - 397
LFTs - 88/136
Cardiac enzymes - 115/2.2/<0.01
Case
EKG – sinus tachycardia at 131, inferolateral TWI
CXR – AP film with just an enlarged cardiac silhouette
Young patient in SHOCK with concerning
cardiac exam and EKG
Case
ECHO:
-
Severely dilated left ventricle but normal wall thickness
No LV thrombus
EF in the 10-15% range
Severe global hypokinesis, with mild posterior wall
contractility.
Moderate to severe MR due to annular dilatation
New onset of Dilated Cardiomyopathy (DCM)
Dilated Cardiomyopathy
www.uptodate.com
Review of 1230 Patients with DCM
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Idiopathic — 50 percent
Myocarditis — 9 percent
Ischemic heart disease — 7 percent
Infiltrative disease — 5 percent
Peripartum cardiomyopathy — 4 percent
Hypertension — 4 percent
HIV infection — 4 percent
Connective tissue disease — 3 percent
Substance abuse — 3 percent
Doxorubicin — 1 percent
Other — 10 percent
NEJM 2000
Importance of Etiology
NEJM 2000
Additional Tests
LABS:
Cardiac CATH:
ESR - 33
Ferritin - nml
TSH - nml
ACE level - nml
RF - nml
ANA - negative
Lyme titers - negative
HIV - negative
Normal Coronaries
What’s the differential?
Any further tests?
Review of 1230 Patients with DCM
Idiopathic — 50 percent
Myocarditis — 9 percent
Ischemic heart disease — 7 percent
Infiltrative disease — 5 percent
Peripartum cardiomyopathy — 4 percent
Hypertension — 4 percent
HIV infection — 4 percent
Connective tissue disease — 3 percent
Substance abuse — 3 percent
Doxorubicin — 1 percent
Other — 10 percent
Endomyocardial
Biopsy
NEJM 2000
Biopsy Results
Dr. Brendan Graham
Dept. of Pathology
Normal Myocardium
Biopsy – 4x
Biopsy – 20x
Biopsy – 40x
Case of Viral Myocarditis

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Other infectious etiologies ruled out by special
stains/cultures
Dallas Criteria:
Lymphocytic infiltrates of varying severity
 Myocyte necrosis and cytoskeletal disorganization
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Interstitial fibrosis seen with subacute/chronic
cases
Objectives: Myocarditis
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Review etiology and pathophysiology
Clinical Manifestations
Role of different diagnostic modalities
Therapy
1.
2.

Cardiovascular support for an unstable patient (i.e.
indications for VAD, ECMO)
Role of immunosuppressive/modulating therapies
Prognosis
Myocarditis
Definition:
Non-ischemic myocardial inflammation resulting
from a variety of infectious, immune and toxic
insults.
Epidemiology
Precise incidence and prevalence unknown
 Lack of a non-invasive “gold standard” test
for diagnosis
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Not every suspected myocarditis case gets a biopsy
Biopsy itself has low sensitivity
Present in 1-9% of routine postmortem
examinations1
Accounted for 20% of sudden cardiac deaths in
military recruits2
1. Circulation 1976
2. Ann Intern Med 2004
Etiology
Infectious
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VIRUSES (adeno,
coxsackie)
Bacterial
Fungal
Protozoal (Chagas
disease)
Helminths
Non-infectious

Toxins/Drugs (alcohol,
anthracyclines)

Systemic disorders
(sarcoid, lupus,
scleroderma)
Etiology
Etiology
Braunwald 2007
Pathophysiology of Viral Myocarditis
Braunwald 2007
Viral Phase
Virus enters (GI/Lungs)
Activates proteases  damages cytoskeletan
Activates tyrosine kinases  immune system turns ON
Replicates and persists  chronic
inflammation/fibrosis/DCM
Braunwald 2007
Immune Response
Autoimmune response: auto-antibodies to myosin and other
cardiac proteins
Overexpression of cytokines (IL-2, INF-γ, TNF-α)
Braunwald 2007
Pathophysiology
Clinical Presentation
Acute
Fulminant

Nonspecific cardiac
symptoms
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
Heart failure, Acute
MI, or SCD

More common in
children/teenagers
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
+/- viral prodrome
Cardiogenic shock
+/- acute heart failure
Chronic
Subtle, insidious
onset

Biopsy doesn’t match  Already have DCM
the clinical severity.
HF symptoms
High levels of
cytokines 
reversible cardiac
depression  better
prognosis
Biopsy with fibrosis
usually

Diagnosis
Symptoms: non-specific
Laboratory Testing: also non-specific
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Positive cardiac biomarkers
ECG: T wave inversion, ST segment elevation, bundle
branch blocks
ECHO
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Differentiate fulminant from acute myocarditis
Detect thrombi, valvular abnormalities, and pericardial
involvement
Rule out other cardiomyopathies (HOCM, Takotsubo)
Diagnosis: Cardiac MRI

Non-invasive

Visualize entire
myocardium

Use to guide biopsy

Follow disease course
and response to therapy
RV
LV
RV
LV
WITHOUT Contrast
WITH Contrast
Eur Heart J 1994
Diagnosis: Coronary
Angiography

Rule out other congenital, rheumatic, or ischemic heart
disease

Determine need for inotropic or mechanical support
based on hemodynamic parameters

Elevated pulmonary artery pressures are independent
predictors of mortality
Diagnosis: Endomyocardial
Biopsy
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Although controversial, still the current gold-standard
test for diagnosis
1-6% complication rate
Consider when suspicious for:
 Giant cell myocarditis
 Hypersensitivity/eosinophilic myocarditis
 Cardiac involvement in a systemic disease
All other patients, consider only if pt is deteriorating
When to consider biopsy?
Mayo Clin Proc 2001
Circulation 2007
Treatment
Dr. Barnett Gibbs
Dept. of Cardiology
Treatment
Treatment
Treatment
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ABC’s
Circulation:
Intra-aortic balloon pump counterpulsation
 Ventricular assist device
 Cardiopulmonary assist device
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Intra-aortic balloon pump
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Electrocardiographic synchronized phased
pulsation
Inflation with aortic valve closure
 Deflation just before systole
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Reduce systolic arterial pressure (afterload)
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Augment diastolic arterial pressure
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Reduces myocardial oxygen consumption
Enhances coronary blood flow
Mean pressure unchanged
Intra-aortic balloon pump
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Benefits:
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Diminish myocardial
ischemia
10-20% increase in CO
Diminish heart rate
Increase urine output
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Risks:
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Damage/perforation of
aorta
Distal ischemia
Thrombocytopenia
Hemolysis
Renal emboli
Mechanical failure –
balloon rupture
Ventricular-assist device
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Centrifugal pump or Archimedes’ screw type
Inflow from LV and outflow into aorta
Has been used as a bridge in myocarditis until
recovery or transplant
*
*Centrifugal pump vs. corkscrew
Ventricular-assist device
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Centrifugal pump or Archimedes’ screw type
Inflow from LV and outflow into aorta
Has been used as a bridge in myocarditis until
recovery or transplant

Disadvantages:
Surgical implantation
 infection
 thrombosis
 hemolysis

Ventricular-assist device

Infection:
Review of 76 patients using LVAD to bridge to
cardiac transplant
 LVAD-related infection:

38 patients (50%)
 29 bloodstream infections (including 5 cases of
endocarditis)
 17 local infections

CID. 2005;40:1108.
Treatment
Treatment


ABC’s
Circulation:
Intra-aortic balloon pump counterpulsation
 Ventricular assist device
 Cardiopulmonary assist device
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Medical therapy
ACE-inhibitors
 Beta-blockers

Medical therapy

Most therapy used in HF patients appears to
benefit those with HF due to myocarditis – with
the exception of digoxin
ACE-inhibitors
 Beta-blockers
 No RCT reviewing spironolactone or ARBs but
these as well as other HF meds have been used
successfully in case reports

Medical therapy

Animal models appear to demonstrate improved
function with use of ACE inhibitors
32 mice infected with Coxsakie B3 virus
 Randomized to captopril vs. placebo on day 3
 This evidence has been extrapolated to humans

Am Heart J. 1990;120:1377.
Medical therapy

Animal models appear to demonstrate improved
function with use of beta-blockers
Circulation. 1991;83:2021..
Treatment
Treatment


ABC’s
Circulation:
Intra-aortic balloon pump counterpulsation
 Ventricular assist device
 Cardiopulmonary assist device


Medical therapy
ACE-inhibitors
 Beta-blockers

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Immunosuppressive therapy
Immunosuppressive Therapies

Recent meta-analysis of placebo-controlled
RCT of immune therapy for myocarditis
 Five
trials; 316 total patients
 Single or combination immunosuppressive
therapy
 Prednisone
 Azathioprine
 Cyclosporine
 IVIG
Int Heart J. 2005;46:113.
Immunosuppressive Therapies
Int Heart J. 2005;46:113.
Immunosuppressive Therapies

End-points:
All cause death
 Heart transplantation
 Secondary:
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Change in LVEF and LVEDD
Summary:

No statistically significant benefit in treatment of
myocarditis with immunosuppressive therapy
Int Heart J. 2005;46:113.
NEJM. 2000;343:1388.
Prognosis

Review of 1230 patients with cardiomyopathy
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Idiopathic cardiomyopathy (n=616 patients)
Peripartum cardiomyopathy (51)
Myocarditis (111)
Ischemic heart disease (91)
Infiltrative myocardial disease (59)
Hypertension (49)
Human immunodeficiency virus (45)
Connective-tissue disease (39)
Substance abuse (37)
Therapy with doxorubicin (15)
Other causes (117)
NEJM. 2000;342:1077.
Prognosis
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Idiopathic CM acted as the reference category
No difference in survival between idiopathic CM and
cardiomyopathy due to myocarditis
NEJM. 2000;342:1077.
Prognosis
NEJM. 2000;342:1077.
Prognosis

“Loose” rule of third’s…
1/3: recover
 1/3: residual ventricular dysfunction
 1/3: transplantation or death
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SUMMARY
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ABC’s
Supportive therapy is mainstay therapy
Most medical therapies for HF seem to benefit
myocarditis patients with the exception of
digoxin
Immunosuppressive therapy does not seem to
play a role in survival
Back to the case
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Stabilized initially with LVAD and ECMO
EF increased to 40-45%
Started on coreg, lisinopril, and aldactone
Multiple complications during the hospital course
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Cardiac tamponade s/p thoracotomy
Hemorrhagic CVA s/p craniotomy, tracheostomy and a PEG
Multiple Infections
Currently, at a rehab facility due to residual neurologic
deficit and deconditioning
Conclusion
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Most common cause is viruses (adeno and coxsackie)
Highly variable clinical manifestations
Cardiac MRI looks promising for diagnosis
Biopsy is the gold standard but should be pursued in
only select patients
Aggressive, supportive care is the first line therapy
because of high incidence of recovery
Immunosuppressive therapy does not affect mortality
References
1.
2.
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4.
5.
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10.
11.
12.
13.
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.
Cooper LT et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease.
Circulation 2007 Nov; 116: 2216-2233.
www.uptodate.com
Baughman KL: Diagnosis of myocarditis: Death of Dallas criteria. Circulation 2006; 113:593.
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
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
Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.
Goldberg LR et al. Predictors of adverse outcome in biopsy-proven myocarditis. JACC 1999; 33
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.
Blankenhorn MA, Gall EA. Myocarditis and myocardosis; a clinicopathologic appraisal. Circulation.
1956;13:217–223.
Kuhl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive
cardiac dysfunction. Circulation. 2005;112:1965–1970.
Fuse K, Kodama M, Okura Y, et al. Predictors of disease course in patients with acute myocarditis. Circulation.
2000;102:2829 –2835.
Ellis CR, et al. Myocarditis basic and clinical aspects. Cardiology in Review 2007;15: 170–177
Biopsy
-
2-5% complication rate


-
Venous access: inadvertent arterial puncture,
pneumothorax, vasovagal reaction, or bleeding after sheath
removal
Procedure itself: arrhythmias, conduction abnormalities,
and cardiac perforation  to pericardial tamponade and
rarely, death.
Patchy infiltrates  lower sensitivity
Lateral wall most common  hard to access
Diagnosis

Expanded Criteria


Category II: Evidence of Cardiac
dysfunction in the Absence of
regional coronary ischemia
Compatible with
myocarditis = 3 positive
categories

Category I: Clinical symptoms
Suspicious for
myocarditis = 2 positive
categories


High probability of
being myocarditis = all 4
categories positive

Category III: Cardiac MRI

Category IV: Myocardial biopsy
- Pathological or Molecular
Analysis