Acute and Fulminant Viral Myocarditis

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Transcript Acute and Fulminant Viral Myocarditis

Case 1

17-year-old girl with a PMHx significant
only for asthma presented with a chief
complaint of fatigue. Her mother noticed
she had been having unintentional weight
loss of 10 pounds over 2 weeks and
brought her to a doctor who diagnosed
her with (asymptomatic) UTI and treated
her with Bactrim. After 1 week, she
represents with fever, abdominal pain,
nausea and vomiting.
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Case 1
A CT of the abdomen and pelvis showed
no abnormalities and she is discharged
with Keflex for pyelonephritis.
 She returns in 24 hours hypotensive with
the following ECG.
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Case 1 : Troponin 13
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Case 1
On arrival to VCU she is hypotensive with
a SBP in the 60-80s despite 4L IVF
 Dobutamine 5mcg/kg/min is running
 HR 140s
 Lactate 7.2
 Troponin >50
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Acute and fulminant
VIRAL Myocarditis
Frances Canet, MD
Cath Conference
August 18, 2011
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Outline
Definition
 Incidence
 Clinical presentation
 Etiologies
 Pathogenesis
 Diagnostics
 Treatment
 Prognosis
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Definition of mycocarditis

Inflammation of the heart muscle
secondary to injury
 Ischemic damage
 Mechanical trauma
 Genetic cardiomyopathies
 Exposure to discrete external antigens
○ Viruses, bacteria, parasites, toxins drugs
 Internal triggers
○ Autoimmune activation against self antigens
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Dallas criteria
Active myocarditis: the presence of an
inflammatory infiltrate of the myocardium
with necrosis and/or degeneration of
adjacent myocytes not typical of the
ischemic damage associated with
coronary artery disease (CAD).
 Borderline myocarditis: the presence of
an inflammatory infiltrate of the
myocardium without necrosis or
degeneration of adjacent myocytes.
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Incidence
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Difficult to ascertain, depends on criteria used
Estimated 8 to 10 per 100,000
Unselected autopsy series as high as 1 to 4
per 100
Young adults with sudden cardiac death,
estimated 8.6%
Idiopathic dilated cardiomyopathy patients
only 10-40% are secondary to
myocarditis
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Population
Bimodal age distribution
 Young children and teenagers: acute
presentation

 Exuberant response to initial exposure of
antigen
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Older adults: Subtle and insidious
symptoms of dilated cardiomyopathy and
heart failure
 Mature immune system with greater tolerance
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Clinical presentation

Wide-ranging clinical presentation
contributes to difficult diagnosis and
classification
 Asymptomatic ECG or echocardiographic
abnormalities
 Cardiac dysfunction, arrhythmias, heart
failure and hemodynamic collapse
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Acute Myocarditis Presentation
Fatigue 82%
 Dyspnea on exertion 81%
 Arrhythmias 55%
 Palpitations 49%
 Chest pain at rest 26%
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Acute Myocarditis Presentation

Acute ischemic syndrome type symptoms
 Elevated troponin
 ST-segment elevation on ECG
 Segmental wall motion abnormalities on
echocardiography

Viral prodrome symptoms 20-80%
 Fever
 Chills
 Myalgias
 Constitutional symptoms
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Fulminant Myocarditis
Presentation
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Abrupt onset within 2 weeks of a viral illness
Hemodynamic compromise
Hypotension requiring pressors and
mechanical support
Echocardiogram reveals diffuse global
hypofunction
Thickening of the ventricular wall probably
due to myocardial edema from myocardial
inflammation and cytokine release
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Case 1
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Endomyocardial biopsy in
fulminant myocarditis
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Typical and diffuse myocarditis in each
histologic section
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Infectious Etiologies
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Non-infectious Etiologies
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Pathogenesis of viral myocarditis
caused by coxsackievirus
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Pathogenesis
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Pathogenesis
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Diagnostics: Expanded Criteria
for Diagnosis of Myocarditis

Category I: Clinical Symptoms
 Clinical heart failure
 Fever
 Viral prodrome
 Fatigue
 Dyspnea on exertion
 Chest pain
 Palpitations
 Pre-syncope or syncope
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Category II: Evidence of Cardiac
Structural or Functional Perturbation in
the absence of Regional Coronary
Ischemia

Echocardiography evidence
 Regional wall motion abnormalities
 Cardiac dilation
 Regional cardiac hypertrophy

Troponin release
 High sensitivity (>0.1 ng/mL)
Positive indium In 111 antimyosin scintigraphy
and
 Normal coronary angiography or
 Absence of reversible ischemia by coronary
distribution on perfusion scan
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Category III: Cardiac Magnetic
Resonance Imaging
Increased myocardial T2 signal on
inversion recovery sequence
 Delayed contrast enhancement after
gadolinium-DTPA infusion
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Category IV: Myocardial biopsy
– Pathologic or Molecular
Analysis
Pathology findings compatible with Dallas
criteria
 Presence of viral genome of polymerase
chain reaction or in situ hybridization
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 80-100% specificity when performed from
myocardial biopsy
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Enzyme biomarkers
Elevated secondary to myocardial
damage from inflammatory cell infiltrates,
cytokine activation and virus- mediated
cell death
 More useful when high sensitivity
thresholds are used
 Troponin T threshold of >0.1mg/mL
increases sensitivity from 34% to 53%
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ECG Findings
T wave inversions
 ST-segment elevation
 Bundle branch block
 Supraventricular arrhythmias
 Ventricular arrhythmias
 47% sensitivity, indeterminate/poor
specificity
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Echocardiography
Regional ventricular dysfunction
 Ventricular remodeling

 Chamber dilation
 Regional hypertrophy
 Regional wall motion abnormalities
May not be able to distinguish from
myocardial ischemia or infarction
 Useful as follow-up to monitor natural history
and response to treatment
 Helps distinguish fulminant from acute
myocarditis
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Cardiac MRI
Characterizes tissue according to water
content and changes in contrast kinetics
(T2 imaging)
 Can detect local patchy nature of
myocarditic lesions
 Extracellular contrast agents such as
gadolinium-DTPA distribute and clear
differently in inflamed or scarred tissue
compared to normal tissue (T1 imaging)
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Cardiac MRI
T2 weighted imaging has a sensitivity of
84% and specificity of 74% based on
biopsy or natural history evidence of
myocarditis
 Delayed enhancement increases
diagnostic accuracy to 90%
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 Deposition of collagen bundles in healing
binds gadolinium and decreases its clearance
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Cardiac MRI
Helpful in guiding biopsy
 CMR suggests the lateral wall is a
common location for lesion development
(not the septum)
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Case 2
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Case 2
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Case 3
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Case 3
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Case 4
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Role of CMR in myocarditis
2009

Indications for CMR include
 New-onset or persisting symptoms
suggestive of myocarditis
 Evidence of recent or ongoing myocardial
injury or dysfunction
 Suspected viral or non-ischemic etiology
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Criteria for myocarditis

At least 2 of the following indicators of
inflammation
 Regional or global myocardial signaling intensity
increase in T2-weighted images
 Increased global myocardial early gadolinium
enhancement between myocardium and skeletal
muscle in gadolinium-enhanced T1 weighted
images
 At least one focal lesion with non-ischemic
regional distribution in inversion recovery
prepared gadolinium-enhanced T1-weighted
images
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Myocardial Biopsy
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The Dallas criteria are the gold standard
for diagnosis, however there are many
reasons for insensitivity
 Patchy nature of disease
 Of postmortem hearts of patients with known
myocarditis, only 25% of single
endomyocardial biopsies showed myocarditis
66% if 5 biopsies were taken
 Most inflammation is in the lateral wall
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The Role of Endomyocardial
Biopsy
AHA/ACC/European Society of
Cardiology released a scientific
statement in 2007 with 14 clinical
scenarios
 Only the first 2 scenarios are class 1
recommendations with B level of
evidence
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Clinical Scenarios for
Biopsy
1. New-onset heart failure of <2 weeks duration
associated with a normal sized or dilated left
ventricle and hemodynamic compromise
2. New-onset heart failure of 2 weeks to 3
months duration associated with a dilated left
ventricle and new ventricular arrhythmias,
second- or third-degree heart block, or failure
to responds to usual care with 1-2 weeks
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Risks of endomyocardial biopsy
Complications occur in 2-5% of patients
with a dilated cardiomyopathy
 Half of these are related to venous
access
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 Arterial puncture
 Pneumothorax
 Vasovagal reaction
 Bleeding after sheath removal
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Risks of endomyocardial biopsy
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Related to the biopsy itself
 Arrhythmias
 Cardiac conduction abnormalities
 Cardiac perforation
○ Pericardial tamponade
 Death
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Molecular evaluation of biopsy
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Combined with Dallas criteria, improves
sensitivity of the biopsy as a diagnostic tool
 Detect viral myocarditis
 Delineate potential viral etiology
In-situ hybridization, PCR
 PCR is limited by requirement of the viral
pathogen must be declared in advance
 Helps with prognosis and to guide therapy
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Treatments/Therapeutic
Approaches
Supportive Therapy
 Immunosuppression
 Interferon
 Intravenous Immune Globulin
 Immune Adsorption Therapy
 Hemodynamic Support
 Vaccination
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Supportive Therapy
First-line therapy
 Only a small proportion of patient require
hemodynamic support
 Treat this group same as for clinical heart
failure
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 Diuretics
 IV Vasodilators: Nitroglycerin, Nesiritide
 ACEi, ARBs, B-blockers when stable
○ Anti-inflammatory properties
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Immunosuppression
Unproven hypothesis
 No shortage of short trials, limited by
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 High degree of spontaneous improvement in
the control and treatment arms
 Small sample size with heterogenous
population
 Patchy nature of myocardial biopsy
 Lack of relationship between pathologic
abnormalities and clinical prognosis
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NIH-sponsored Myocardial
Treatment Trial
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Interferon
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Type 1 interferons (IFN- and IFN-
phosphorylate interferon-stimulated genes in the
host innate immune systemdegradation of
foreign viral RNA and interfere with accumulation
of viral RNA

2003, Kuhl et. Al. evaluated 22 patients with
dilated cardiomyopathy and biopsy evidence of
viral persistence
 24 weeks of IFN-
 Eliminated the viral genome in all 22 patients
 LVEF improved from 44.6% to 53.1% in 15 of 22
patients.
 NYHA class also improved
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Intravenous Immune Globulin
Passive immunization with IVIG
 2001 Controlled trial of IVIG in recentonset dilated cardiomyopathy, McNamara
et. Al.
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62 patients
IVIG or Placebo
LVEF improved 25 to 41% at 6 months
LVEF improved to 42% at 12 months
Same improvement seen in both IVIG and
Placebo group
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Intravenous Immune
Globulin
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No primary indication except:
 Pediatric population
 Patients refractory to immunosuppressive
therapy
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Need to obtain viral studies prior to
administering
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Immune Adsorption Therapy
Plasmapheresis of peripheral blood
 Cytokines, circulating antibodies may
target specific components of the
myocyte under stress
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 Beta-adrenergic receptor
 ATP carrier
 Myosin molecule
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Leads to cell dysfunction and cell death
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2001 Immunohistological changes in dilated
cardiomyopathy induced by immunoadsorption
therapy and subsequent immunoglobulin
substitution, Staudt at. al
34 patients, randomized
 Standard therapy or immune adsorption
therapy aimed at removal of antibodies
against the beta-adrenergic receptor
 After 1 year, treatment group LVEF
improved from a mean of 22 to 38%.
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Hemodynamic Support
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Patients with fulminant myocarditis and
cardiogenic shock may require
 Intra-aortic balloon pump
 Ventricular assist devices
 Extracoporeal membrane oxygenation
(ECMO)
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Vaccination
Targeted vaccination in the future
 Patients genetically susceptible to
myocarditis
 After the mumps vaccination
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 Disappearance of endocardial fibroelastosis
causing dilated cardiomyopathy
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Prognosis
Most patients with acute myocarditis and mild
cardiac involvement recover without long-term
sequelae
 Patient with advance cardiac dysfunction,
varied outlook
 Patients with severe hemodynamic collapse
at presentation actually have a good
prognosis
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 93% transplant-free survival in 11 years
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30% of those with chronic myocarditis may
recover
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Prognosis
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Several studies have looked at clinical variables
that predict adverse outcomes (death and
transplantation)
 Syncope
 Bundle branch block
 EF <40%
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Other factors
 NYHA Class III or IV
 PCWP <15mmHg
 Immunopathologic evidence of myocardial
inflammation
 Failure to use B-blockers
 BiV failure
 Giant cell or viral genome on biopsy
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Other poor prognostic signs
Dilated cardiomyopathy with positive
enteroviral genome
 Viral genome persistence on myocardial
biopsy
 Excessive apoptosis
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 Myocardial expression of Fas ligand or tumor
necrosis factor receptor 1 showed minimal
recovery
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Good prognosis

Echo evidence of small left atrial and LV
size was predictive of recovery in one
small study
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Summary
Myocarditis is a model study of host
injury and repair
 Diagnosis was classically dependent on
Dallas criteria
 Newer modalities of testing such as
cardiac MRI and PCR will help pinpoint
diagnosis thus facilitating treatment and
prognosis
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Summary
Understanding the pathophysiologic
mechanisms of infection and injury has
led to new treatments.
 Interferon and immune-modifying agents
as well as advanced modes of
hemodynamic support will offer patients
the best chances of full recovery.
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