MIOCARDITE & CARDIOMIOPATII

Myocarditis
Inflammation
Resulting in injury to cardiac myocytes (necrosis and/or

degeneration) not typical of IHD

Inflammation of myocardium, that can be caused by: Drugs. Pathogen: Bacteria, Fungus, Virus, Immune reaction. Deposition of certain substances.

Infections Cardiac allograft rejection Collagen vascular diseases Drug hypersensitivity Sarcoidosis

These cause inflammatory reaction & cell damage in myocarditis NOT in ischemic disease.

Myocarditis
Infectious Etiologic Agents

Viruses (most common cause in USA)

Can effect young age group.

Coxsackieviruses A & B and other enteroviruses (most common agents) Cytomegalovirus HIV
HIV Myocarditis.

Other

Myocarditis
Infectious Etiologic Agents

Parasites

Chagas disease (Trypanosoma cruzi)

Epidemiologically is found in South America (Brazil).

Toxoplasmosis Trichinosis
T.Spiralis.

Myocarditis
Infectious Etiologic Agents

Bacteria
The injury is by their toxins.

Lyme disease
Due to Spirochete infection. It causes arthritis, fever & skin rash.

Diphtheria (injury from toxins of Corynebacterium diphtheriae)

Associated with weakness, hypovolemia & heart failure. When examining the heart there will be NO Bacteria.

Viral Infection
Coxsackie (A, B) Echo Influenza (A, B) Polio Herpes simplex Varicella-zoster Epstein-Barr Cytomegalovirus Rubella Rubeola Vaccinia Coronavirus Rabis Hepatitis B Arbovirus Junin virus

Mumps

Human immunodeficiency

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Bacterial, rickettsial, spirochetal

Corynebacterium Chlamydia trachomatis Mycoplasma pneumoniae Chlamydia psittaci

diphtheriae salmonella typhi Beta-hemolytic streptococci Neisseria meningitidis Legionella pneumophila Listeria monocytogenes Camphylobacter jejuni Coxiella burnetii (Q fever)

(psittacosis) Rickettsia rickettsii (Rocky Mountain spotted fever) Borrelia burgdorferi (Lyme disease) Mycobacterium tuberculosis
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Protozoal, Metazoal, Fungal

Protozoal Trypnosoma cruzi (Chagas disease) Toxoplasma gondi Fungal Aspergillosis Blastomycosis Candidiasis Coccidioidomycosis Cryptococcosis Histoplasmosis Mucormycosis

Metazoal Trichinosis Ehinococcosis

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Noninfectious
Systemic Diseases: 1. SLE 2. Sarcoidosis 3. Vasculitides(Wegeners) 4. Celiac disease

Neoplastic infiltration
Drugs & toxins: 1. Ethanol 2. Cocaine 3. Radiation 4. Chemotherapeutic agents - Doxorubicin

Drugs Causing Hypersensitivity Myocarditis

Diuretics Antibiotics Anticonvulsants acetazolamide chlorthalidone amphoericin B phenindione hydrochlorothiazide ampicillin phenytoin spironolactone Other chloramphenic carbamazepine amitriptyline methyldopa ol Antitubercuous sulfonylureas penicillin tetanus toxoid isoniazid tetracycline paraaminosalicylate streptomycin Anti-inflammatory Sulfonamides indomethacin sufadiazine oxyphenbutazone sufisoxazole phenylbutazone
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Myocarditis
Morphology (Gross)

Cardiac dilation Myocardium flabby, pale, with focal

hemorrhages
The myocardium will be flabby (soft), weak & the patient will have sever heart failure.

The heart is congested, edematous, flabby, soft, dailated & weak in pumping.

Myocarditis
Morphology (Microscopic)
Acute viral

Edema Inflammatory infiltrate of lymphocytes and other mononuclear cells Myocyte degeneration and/or necrosis Viral inclusions may be present
Parasitic

Organisms identified
Bacterial

Neutrophilic inflammatory infiltrate

Histology: there are edema, inflammatory exudates, damage to cells & inclusions of Virus or Bacteria.

Toxoplasma.

Giant cell myocarditis

Fiedlers myocarditis
MN giant cells Lymphocytes, eosinophils, necrosis Differential: Sarcoid, hypersensitivity,TB Aggressive clinical course: indication for

transplant
Giant cell myocarditis is granulomatous reaction.

Giant cell.

Hypersensitivity myocarditis
Interstitial infiltrate of macrophages, eosinophils

No or little necrosis
No granulomas, but multinucleated cells may be present

Fewer clinical manifestations than other forms of myocarditis

Associated with long list of drugs (classically,

methyldopa)

Eosinophils.

Cardiac sarcoidosis
Cardiac involvement in 20-30% of patients with

clinical sarcoid at autopsy 5% of sarcoid patients will have symptomatic heart disease (cardiomyopathy, arrhythmias) Sites of predilection: IVS, LV free wall, but all sites, including pericardium, may be involved
Sarcoidosis is multi-systemic granulomatous disease that produces Non-Caseating / NonNecrotising granuloma in lymph nodes, liver, spleen, lungs & heart. When arrhythmia develops, the conduction system of myocardium is involved (Pirkenje fibers & nodes).

Rheumatic carditis
Uncommon cause of myocarditis
Aschoff nodule
Anitschkow cell

Macrophages
Collagenolysis Interstitial fibrosis

Pancarditis
Rheumatic carditis: disease of the endo-cardium (valves: chordae tendineae & cusps).

Clinical Presentation
may be asymptomatic, inferred only from ST-T

changes on the ECG May also present as a fulminant condition characterized by heart failure and arrhythmias and death May simulate AMI and have elevated cardiac enzymes PE is often normal but in the severe forms may have S3 and murmur of MR

Clinical Presentation
May be self limited without any sequelae but

severe involvement may occur Likely progresses to a chronic form and to dilated cardiomyopathy Patients with viral myocarditis often present with flulike illness Patients who present with CHF may respond to usual measures Death due to arrhythmias had been reported

Clinical Manifestations
Most cases of acute myocarditis are clinically silent
60% of pts had antecedent flulike symptoms

Large number identified by heart failure symptoms

35% of pts with myocarditis and HF have chest

pain May mimic an acute MI with ventricular dysfunction, ischemic chest pain, ECG evidence of injury or Q waves
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Clinical Manifestations
May present with syncope, palpitation with AV block or ventricular arrhythmia
May cause sudden death
myocarditis found at autopsy in 20% of Air Force

recruits with sudden death*

May present with systemic or plumonary thromboembolic disease

JAMA 1986; 256:2696-2699

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Blood studies
Sed rate elevation
White count elevation CK-MB elevation

60% 25% 12%

a 4 fold rise in IgG titer over a 4-6 wk period is required to document an acute viral infection

Heart specific antibodies are nonspecific for myocarditis; also found in dilated cardiomyopathy
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Electrocadiogram
sinus tachycardia is most common
diffuse ST-T wave changes myocardial infarction pattern

conduction delay and LBBB in 20%

complete heart block causing Stokes-Adams attacks (particularly in Japan), but rarely require a

permanent pacer supraventricular and ventricular arrhythmias

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Myocarditis

H9925 9-8-98
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H9925 8-30-98
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Echocardiography
Useful tool in managing patients with acute myocarditis
LV systolic dysfuntion is common with segmental

wall motion abnormalities LV size is typically normal or mildly dilated wall thickness may be increased ventricular thrombi detected in 15%

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Endomyocardial Biopsy
RV bioptome permit repetitive sampling
biopsy should be applied early after onset of

symptoms to maximize yield - resolution may be seen in four days on serial biopsies Dallas criteria for active myocarditis an inflammatory infiltrate of the myocardium with
necrosis and/or degeneration of adjacent myocytes not typical of the ischemic changes associated with coronary artery disease
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Clinical Indications for Endomyocardial Biopsy

Definite
monitoring of cardiac allograft rejection monitoring of anthracycline cardiotoxicity

Possible
detection and monitoring of myocarditis diagnosis of secondary cardiomyopathies

differentiation between restrictive and constrictive

heart disease

Two-dimensional parasternal long-axis view depicting disproportionate thickening, increased echogenicity, and dyskinesis of the inferolateral wall relative to the septum; findings are consistent with tissue oedema.

Imaging Studies
Gallium 67 (avid for inflammation) showed promise for screening active myocarditis
Indium 111-antimyosin monoclonal antibody

(avid for injured myocardium) sensitivity 83% specificity 53% + predictive value 92% endomyocardial biopsy remains the diagnostic standard
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Gallium-67 scintigraphy of the myocardium, showing on top, a positive study, with hypercaptation on the heart projection and, on the bottom, a negative study

The delayed contrast enhanced image of the same patient showed diffuse hyperenhanced areas in the typical midmyocardial location (). LV: left ventricle. RV: right ventricle

Myocardial Treatment Trial

111 patients with active myocarditis
Age
Sex Ejection fraction Chest pain Increase MB-CK Flulike symptoms Increased ESR Elevated WBC Fever

42 14 years
62% male 0.24 0.10 35% 12% 59%

61% 24%
18%
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Circulation 1991;84(suppl II):II-2

38

Treatment
majority of patients have a self-limited disease
management of LV dysfunction similar to other forms of congestive heart failure

? exercise may intensify inflammatory response

consider anticoagulation to prevent thromboemboli

consider temporary pacer for complete AV block

? prednisone and azathioprine - no apparent benefit seen in the Myocarditis Treatment Trial
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CARDIOMYOPATHIES

Definition
A primary disorder of the heart muscle that causes abnormal myocardial performance and is not the result of disease or dysfunction of other cardiac structures myocardial infarction, systemic hypertension, valvular stenosis or regurgitation

Cardiomyopathies

Definition: Heart muscle disorder of unknown etiolog

Disease of myocardium; the muscle it self (myocyte).

Diagnosis of exclusion
Excluding the causes: ischemia, drugs, virus,

Confusion (some exclude any disorder of known etiology, while some do not) Dilated (congestive) (90%)
Commonest type. Big heart on chest X-Ray. Patient comes with heart failure.

Can be divided to 3 groups:

1.

1. 2.

Hypertrophic (< 10%) Restrictive (< 2%)

Least common.

Classification
Etiology- primary or secondary gross anatomy histology genetics biochemistry immunology hemodynamics functional prognosis treatment

Primary cardiomyopathies in which the clinically relevant disease processes solely or predominantly involve the myocardium

Maron, B. J. et al. Circulation 2006;113:1807-1816

Copyright 2006 American Heart Association

Functional Classification
Dilatated (congestive, DCM, IDC)
ventricular enlargement and syst dysfunction

Hypertrophic (IHSS, HCM, HOCM)

inappropriate myocardial hypertrophy

in the absence of HTN or aortic stenosis

Restrictive (infiltrative)
abnormal filling and diastolic function

IDIOPATHIC DILATED CARDIOMYOPATHY

Definition
a disease of unknown etiology that principally

affects the myocardium

Diagnosis by exclusion. LV and/or right dilatation and systolic dysfunction, arrhythmias, heart failure pathology
increased heart size and weight ventricular dilatation, normal wall thickness heart dysfunction out of portion to fibrosis

Incidence and Prognosis

3-10 cases per 100,000
20,000 new cases per year in the U.S.A. death from progressive pump failure 1-year 25% 2-year 35-40% 5-year 40-80% stabilization observed in 20-50% of patient complete recovery is rare

Idiopathic Dilated Cardiomyopathy

Observed Survival of 104 Patients
120 100 80 60 40 20 0 0 1 2 3 4 5 6 7 8 9 10 104

72 56 51 45

37

35

31

24

19

16

Years
Am J Cardiol 1981; 47:525

Predicting Prognosis in IDC

Predictive
Clinical factors symptoms

Possible
alcoholism peripartum family history LV size atrial pressure AV block atrial fibrillation myofibril volume

Not Predictive
age duration viral illness

Hemodynamics

Dysarrhythmia
Histology Neuroendocrine

LVEF Cardiac index LV cond delay complex VPC

simple VPC
other findings

hyponatremia plasma norepinephrine atrial natriuretic factor

Dilated Cardiomyopathy
Morphology (Gross) Heart enlarged and flabby Weight may exceed 900 grams

Dilation & hypertrophy of all four chambers

Mural thrombi due to stasis
CAD minimal or absent

Normal heart.

Dilated cardiomyopathy.

Core povenum ( like heart of a cow).

Dilated Cardiomyopathy
Morphology (Microscopic)
Nonspecific Myocyte hypertrophy Interstitial fibrosis Wavy fiber change or myofiber loss Scanty mononuclear inflammatory infiltrate

Clinical Manifestations
Highest incidence in middle age
blacks 2x more frequent than whites men 3x more frequent than women

symptoms may be gradual in onset acute presentation

misdiagnosed as viral URI in young adults

uncommon to find specific myocardial disease on

endomyocardial biopsy

History and Physical Examination

Symptoms of heart failure
pulmonary congestion (left HF)

dyspnea (rest, exertional, nocturnal), orthpnea systemic congestion (right HF) edema, nausea, abdominal pain, nocturia low cardiac output fatigue and weakness

hypotension, tachycardia, tachypnea, JVD

Cardiac Imaging
Chest radiogram

Electrocardiogram
24-hour ambulatory ECG (Holter)
lightheadedness, palpitation, syncope

Two-dimensional echocardiogram
Radionuclide ventriculography Cardiac MRI

Cardiac catheterization
age >40, ischemic history, high risk profile, abnormal

ECG

Management of DCM
Limit activity based on functional status
salt restriction of a 2-g Na+ (5g NaCl) diet fluid restriction for significant low Na+

initiate medical therapy

ACE inhibitors, diuretics digoxin, carvedilol

hydralazine / nitrate combination

Management of DCM
consider adding -blocking agents if symptoms persists
anticoagulation for EF <30%, history of

thromboemoli, presence of mural thrombi intravenous dopamine, dobutamine and/or phosphodiesterase inhibitors cardiac transplantation

HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic Cardiomyopathy
First described by the French and Germans around 1900
uncommon with occurrence of 0.02 to 0.2% a hypertrophic and non-dilated left ventricle in the absence of another disease

small LV cavity, asymmetrical septal

hypertrophy (ASH), systolic anterior motion of the mitral valve leaflet (SAM)

Hypertrophic Cardiomyopathy

Autosomal dominant Abnormalities in the Beta myosin heavy chain.

Hypertrophic Cardiomyopathies
Predominant Features
Asymmetric hypertrophy of the LV Normal ventricular systolic function Impaired LV diastolic function +/- Subaortic dynamic obstruction

CAUSES OF CARDIAC HYPERTROPHY

1. Pressure overload

hypertension, valvular stenosis (aortic stenosis)

2. Volume overload

valvular insufficiency
3. Myocardial injury

M.I., myocarditis, cardiomyopathy

MI & myocarditis: damage to a part of myocardium, the other parts will compensate by under going hypertrophy.

Septum. Hypertrophy in all the layers in every whereConcentric hypertrophy. Commonest cause is long standing systemic hypertension. Pressure over-load in the aortic valve stenosis or regurgitation that will end up in dilatation & heart failure.

Hypertrophic Cardiomyopathy
Morphology (Microscopic)
Haphazard arrangement of

hypertrophied myocytes, surrounded by loose, basophilic ground substance Myocardial fibrosis may occur late

 Very thick fibers.

Hypertrophic Cardiomyopathies
Type I II III Feature Hypertrophy confined to Anterior segment of the IVS Hypertrophy confined to Anterior and Inferior segments of the IVS Extensive hypertrophy of LV with sparing of the basal segment of the posterior wall. Apical hypertrophy

IV

Hypertrophic Cardiomyopathies

Familial HCM
First reported by Seidman et al in 1989 occurs as autosomal dominant in 50% 5 different genes on at least 4 chromosome

with over 3 dozen mutations

chromosome 14 (myosin) chromosome 1 (troponin T) chromosome 15 (tropomyosin) chromosome 11 (?)

Pathophysiology
Systole
dynamic outflow tract gradient

Diastole
impaired diastolic filling, filling pressure

Myocardial ischemia

muscle mass, filling pressure, O2 demand vasodilator reserve, capillary density abnormal intramural coronary arteries systolic compression of arteries

Clinical Manifestation
Asymptomatic, echocardiographic finding
Symptomatic
dyspnea in 90%

angina pectoris in 75%

fatigue, pre-syncope, syncope

risk of SCD in children and adolescents palpitation, PND, CHF, dizziness less frequent

Natural History
annual mortality 3% in referral centers probably closer to 1% for all patients
risk of SCD higher in children

may be as high as 6% per year majority have progressive hypertrophy clinical deterioration usually is slow progression to DCM occurs in 10-15%

Risk Factors for SCD

Young age (<30 years)
Malignant family history of sudden death Gene mutations prone to SCD (ex. Arg403Gln)

Aborted sudden cardiac death

Sustained VT or SVT Recurrent syncope in the young

Nonsustained VT (Holter Monitoring)

Brady arrhythmias (occult conduction disease)
Br Heart J 1994; 72:S13

Recommendations for Athletic Activity

Avoid most competitive sports (whether or

not symptoms and/or outflow gradient are present)

Recommendations for Athletic Activity

Low-risk older patients (>30 yrs) may participate in

athletic activity if all of the following are absent

ventricular tachycardia on Holter monitoring family history of sudden death due to HCM history of syncope or episode of impaired consciousness severe hemdynamic abnormalities, gradient 50 mmHg exercise induced hypotension moderate or sever mitral regurgitation enlarged left atrium (50 mm) paroxysmal atrial fibrillation abnormal myocardial perfusion

Management
beta-adrenergic blockers
calcium antagonist disopyramide

amiodarone, sotolol
DDD pacing myotomy-myectomy plication of the anterior mitral leaflet

HCM vs Aortic Stenosis

HCM
carotid pulse murmur spike and dome valsalva, standing squatting, handgrip passive leg elevation 4th left interspace absent

Fixed Obstruction
parvus et tardus radiate to carotids

systolic thrill systolic click

2nd right interspace present

Other Causes of Hypertrophy

Clinical mimics
glycogen storage, infants of diabetic mothers, amyloid

Genetic
Noonans, Friedreichs ataxia, Familial restrictive

cardiomyopathy with disarray Exaggerated physiologic response Afro-Caribbean hypertension, old age hypertrophy, athletes heart

HCM vs Athletes Heart

HCM + + + + + + +
Unusual pattern of LVH LV cavity <45 mm LV cavity >55 mm LA enlargement Bizarre ECG paterns Abnormal LV filling Female gender thickness with deconditioning Family history of HCM
Circulation 1995; 91:1596

Athlete + + -

Hypertensive HCM of the Elderly

Characteristics
modest concentric LV hypertrophy (<22 mm) small LV cavity size

associated hypertension
ventricular morphology greatly distorted with

reduced outflow tract sigmoid septum and grandma SAM

RESTRICTIVE CARDIOMYOPATHY

Restrictive Cardiomyopathies
Hallmark: abnormal diastolic function
rigid ventricular wall with impaired ventricular

filling bear some functional resemblance to constrictive pericarditis importance lies in its differentiation from operable constrictive pericarditis

Restrictive Cardiomyopathy
Description
Primary decrease in ventricular

compliance, resulting in impaired ventricular filling during diastole

Restricting the heart movement.

Constrictive / restrictive precarditis precardium is enclosed in fibrous wall.

Least common type of cardiomyopathy

Restrictive Cardiomyopathy
Causes 1. Endomyocardial fibrosis Most common cause worldwide 10% of cases of childhood heart disease in tropical regions
The heart becomes less compliance due to fibrosis during diastole the heart will not dilate properly.

2. Infiltrative heart disease (amyloid,

HH)Hemosedrin deposition. 3. Idiopathic

Restrictive Cardiomyopathy
Morphology (Gross)
Varies depending on cause

Atrial dilation (bilateral)

Endocardium thickened and opaque Valvular thickening

Mural thrombi may be present

Morphology (Microscopic)
Dense endocardial fibrosis, extending into subendocardial

myocardium Eosinophils in some cases

Dilated atria.

Idiopathic restrictive cardiomyopathy: Biatrial dilatation, grossly normal ventricles

Classification
Idiopathic

Myocardial

1. Noninfiltrative Idiopathic Scleroderma 2. Infiltrative Amyloid Sarcoid Gaucher disease Hurler disease

3. Storage Disease Hemochromatosis Fabry disease Glycogen storage

Endomyocardial
endomyocardial fibrosis Hyperesinophilic synd Carcinoid

metastatic malignancies
radiation, anthracycline

Clinical Manifestations
Symptoms of right and left heart failure
Jugular Venous Pulse
prominent x and y descents

Echo-Doppler
abnormal mitral inflow pattern prominent E wave (rapid diastolic filling) reduced deceleration time ( LA pressure)

Constrictive - Restrictive Pattern Square-Root Sign or Dip-and-Plateau

Restriction vs Constriction
History provides important clues Constrictive pericarditis
history of TB, trauma, pericarditis, sollagen

vascular disorders

Restrictive cardiomyopathy
amyloidosis, hemochromatosis

Mixed
mediastinal radiation, cardiac surgery

Treatment
No satisfactory medical therapy
Drug therapy must be used with caution
diuretics for extremely high filling prssures

vasodilators may decrease filling pressure

? Calcium channel blockers to improve diastolic

compliance digitalis and other inotropic agents are not indicated

Cardiac amyloid
Three main types
AL (light chains, plasma cell dyscrasias) AA (chronic inflammatory diseases, rare in heart) AS (transthyretin, senile amyloid)

Pathology
10 nm non-branching extracellular fibrils Homogeneous waxy material present in interstitium,

vessels or nodular Congo red positive, apple green birefringence

Clinical Setting
Constrictive vs. restrictive disease patient presents with
congested neck veins, synosis & edema. Amyloid causes malignancy called Multiple Myloma.

 Deposition of amyloid fibers.

Hemochromatosis
Iron not normally found in heart

Pathology
Perinuclear distribution Epicardial portions preferentially involved C282Y or H63D mutation (chromosome 6) HLA-associated TfR gene

Clinical Setting
Dilated or restrictive cardiomyopathy
Hemochromatosis: iron deposition in all orgens.

Iron deposition.

Drug-induced cardiomyopathy
Adriamycin commonest drug. Other drugs (chloroquine,

amiodarone)
These drugs treat cancer & are cardiotoxic.

Arrhythmogenic RV Dysplasia
Uncommon, familial form that affects young

adults causing sudden death RV is markedly thinned & replaced by fat CPC required (fat may be seen in normal)