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

Dilated Cardiomyopathy

www.uptodate.

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
NEJM

Importance of Etiology

NEJM

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

Whats 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
Endomyocar
Peripartum cardiomyopathy 4 percent dial
Hypertension 4 percent
Biopsy
HIV infection 4 percent
Connective tissue disease 3 percent
Substance abuse 3 percent
Doxorubicin 1 percent
Other 10 percent
NEJM

Biopsy Results
Dr. Brendan Graham
Dept. of Pathology

Normal Myocardium

Biopsy 4x

Biopsy 20x

Biopsy 40x

Case of Viral Myocarditis

Other infectious etiologies ruled out

by special stains/cultures
Dallas Criteria:
Lymphocytic infiltrates of varying
severity
Myocyte necrosis and cytoskeletal
disorganization

Interstitial fibrosis seen with

subacute/chronic cases

Objectives: Myocarditis

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

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

Etiology
Infectious

VIRUSES (adeno,
coxsackie)
Bacterial
Fungal
Protozoal (Chagas
disease)
Helminths

Non-infectious

Toxins/Drugs
(alcohol,
anthracyclines)

Systemic disorders
(sarcoid, lupus,
scleroderma)

Etiology

Etiology

Braunwald

Pathophysiology of Viral
Myocarditis

Braunwald 20

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

Immune Response

Autoimmune response: auto-antibodies to myosin

and other cardiac proteins
Overexpression of cytokines (IL-2, INF-, TNF-)

Braunwald

Pathophysiology

Clinical Presentation
Acute
Nonspecific
cardiac
symptoms

Fulminant
Cardiogenic
shock +/- acute
heart failure

Chronic
Subtle,
insidious onset

Already have
Heart failure,
Biopsy doesnt
DCM HF
Acute MI, or SCD match the clinical symptoms
severity.

More common
High levels of
in
children/teenager cytokines
s
reversible
cardiac
depression
+/- viral

Biopsy with
fibrosis usually

Diagnosis
Symptoms: non-specific
Laboratory Testing: also non-specific

Positive cardiac biomarkers

ECG: T wave inversion, ST segment elevation,
bundle branch blocks

ECHO

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 19

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

Although controversial, still the current goldstandard 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

Circulation

Treatment
Dr. Barnett Gibbs
Dept. of Cardiology

Treatment

Treatment

Treatment

ABCs
Circulation:
Intra-aortic balloon pump counterpulsation
Ventricular assist device
Cardiopulmonary assist device

Intra-aortic balloon
pump

Electrocardiographic synchronized
phased pulsation
Inflation with aortic valve closure
Deflation just before systole

Reduce systolic arterial pressure

(afterload)

Augment diastolic arterial pressure

Reduces myocardial oxygen consumption

Enhances coronary blood flow

Mean pressure unchanged

Intra-aortic balloon
pump

Benefits:

Diminish
myocardial
ischemia
10-20% increase in
CO
Diminish heart rate
Increase urine
output

Risks:

Damage/perforatio
n of aorta
Distal ischemia
Thrombocytopenia
Hemolysis
Renal emboli
Mechanical failure
balloon rupture

Ventricular-assist device

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

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

ABCs
Circulation:
Intra-aortic balloon pump counterpulsation
Ventricular assist device
Cardiopulmonary assist device

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

ABCs
Circulation:
Intra-aortic balloon pump counterpulsation
Ventricular assist device
Cardiopulmonary assist device

Medical therapy
ACE-inhibitors
Beta-blockers

Immunosuppressive therapy

Immunosuppressive
Therapies

Recent meta-analysis of placebocontrolled 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:

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

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

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 thirds

1/3: recover
1/3: residual ventricular dysfunction
1/3: transplantation or death

SUMMARY

ABCs
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

Stabilized initially with LVAD and ECMO

EF increased to 40-45%
Started on coreg, lisinopril, and aldactone
Multiple complications during the hospital
course

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

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
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.
2.
Cooper LT et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular
Disease. Circulation 2007 Nov; 116: 2216-2233.
3.
www.uptodate.com
4.
BaughmanKL: Diagnosis of myocarditis: Death of Dallas criteria. Circulation
2006;113:593.
5.
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
6.
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
7.
Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.
8.
Goldberg LR et al. Predictors of adverse outcome in biopsy-proven myocarditis. JACC 1999;
33
9.
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;141:829834.
10. Blankenhorn MA, Gall EA. Myocarditis and myocardosis; a clinicopathologic appraisal.
Circulation. 1956;13:217223.
11. Kuhl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated
with progressive cardiac dysfunction. Circulation. 2005;112:19651970.
12. Fuse K, Kodama M, Okura Y, et al. Predictors of disease course in patients with acute
myocarditis. Circulation. 2000;102:2829 2835.
13. Ellis CR, et al. Myocarditis basic and clinical aspects. Cardiology in Review 2007;15:
170177
1.

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

Suspicious for
myocarditis = 2
positive categories

symptoms

Category II: Evidence of

Cardiac dysfunction in the

Absence of regional coronary
ischemia

Compatible with
myocarditis = 3
positive categories
High probability of
being myocarditis = all
4 categories positive

Category I: Clinical

Category III: Cardiac MRI

Category IV: Myocardial

biopsy - Pathological or
Molecular Analysis