CURS MEDICINA INTERNA

ANUL IV
 MIOCARDITE SI
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 These cause
inflammatory reaction
• Cardiac allograft rejection & cell damage in
• Collagen vascular diseases myocarditis NOT in
ischemic disease.
• Drug hypersensitivity
• Sarcoidosis
 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) • Rubella
• Echo • Rubeola
• Influenza (A, B) • Vaccinia

11/98
• Polio • Coronavirus

medslides.com
• Herpes simplex • Rabis
• Varicella-zoster • Hepatitis B
• Epstein-Barr • Arbovirus
• Cytomegalovirus • Junin virus
• Mumps • Human
immunodeficiency
7
Bacterial, rickettsial, spirochetal
• Corynebacterium • Chlamydia trachomatis
diphtheriae • Mycoplasma
• salmonella typhi pneumoniae

11/98
• Beta-hemolytic • Chlamydia psittaci
streptococci (psittacosis)

medslides.com
• Neisseria meningitidis • Rickettsia rickettsii
• Legionella pneumophila (Rocky Mountain spotted
• Listeria monocytogenes fever)
• Camphylobacter jejuni • Borrelia burgdorferi
(Lyme disease)
• Coxiella burnetii (Q
fever) • Mycobacterium
tuberculosis 8
Protozoal, Metazoal, Fungal
Protozoal Fungal
• Trypnosoma cruzi • Aspergillosis
(Chagas’ disease) • Blastomycosis

11/98
• Toxoplasma gondi • Candidiasis

medslides.com
• Coccidioidomycosis
Metazoal • Cryptococcosis
• Trichinosis • Histoplasmosis
• Ehinococcosis • Mucormycosis

9
Noninfectious

Systemic Diseases:
1. SLE
2. Sarcoidosis
3. Vasculitides(Wegener’s)
4. Celiac disease
Neoplastic infiltration

Drugs & toxins:

1. Ethanol
2. Cocaine
3. Radiation
4. Chemotherapeutic agents - Doxorubicin
Drugs Causing
Hypersensitivity Myocarditis

Antibiotics Anticonvulsants Diuretics

acetazolamide
amphoericin B phenindione chlorthalidone

11/98
ampicillin phenytoin hydrochlorothiazide
spironolactone
chloramphenic carbamazepine

medslides.com
Other
ol Antitubercuous amitriptyline
methyldopa
penicillin isoniazid sulfonylureas
tetracycline paraaminosalicylate
tetanus toxoid

streptomycin Anti-inflammatory
Sulfonamides indomethacin
sufadiazine oxyphenbutazone
sufisoxazole phenylbutazone
11
 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
• “Fiedler’s” 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 / Non-
Necrotising 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

11/98
• 60% of pts had antecedent flulike symptoms
• Large number identified by heart failure

medslides.com
symptoms
• 35% of pts with myocarditis and HF have chest
pain
• May mimic an acute MI with ventricular
dysfunction, ischemic chest pain, ECG evidence
25
of injury or Q waves
Clinical Manifestations
• May present with syncope, palpitation with AV
block or ventricular arrhythmia

11/98
• May cause sudden death
• myocarditis found at autopsy in 20% of Air Force

medslides.com
recruits with sudden death*
• May present with systemic or plumonary
thromboembolic disease

26

JAMA 1986; 256:2696-2699

Blood studies
• Sed rate elevation 60%
• White count elevation 25%

11/98
• CK-MB elevation 12%

medslides.com
• 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
27
Electrocadiogram
• sinus tachycardia is most common
• diffuse ST-T wave changes

11/98
• myocardial infarction pattern

medslides.com
• 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
28
Myocarditis

11/98
medslides.com
29

H9925 9-8-98
H9925 8-30-98

medslides.com 11/98
30
Echocardiography
• Useful tool in managing patients with acute myocarditis
• LV systolic dysfuntion is common with segmental wall motion
abnormalities

11/98
• LV size is typically normal or mildly dilated
• wall thickness may be increased

medslides.com
• ventricular thrombi detected in 15%

31
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

11/98
biopsies
• Dallas criteria for active myocarditis

medslides.com
“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”

32
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

11/98
• Indium 111-antimyosin monoclonal antibody
(avid for injured myocardium)

medslides.com
sensitivity 83%
specificity 53%
+ predictive value 92%
• endomyocardial biopsy remains the diagnostic
standard
35
 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 42  14 years
Sex 62% male
0.24  0.10

11/98
Ejection fraction
Chest pain 35%

medslides.com
Increase MB-CK 12%
Flulike symptoms 59%
Increased ESR 61%
Elevated WBC 24%
Fever 18%
39

Circulation 1991;84(suppl II):II-2

Treatment
• majority of patients have a self-limited disease
• management of LV dysfunction similar to other

11/98
forms of congestive heart failure
• ? exercise may intensify inflammatory response

medslides.com
• consider anticoagulation to prevent
thromboemboli
• consider temporary pacer for complete AV block
• ? prednisone and azathioprine - no apparent
benefit seen in the Myocarditis Treatment Trial 40
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)
Can be divided to 3 groups:
1. Dilated (congestive) (90%)
•Commonest type.
•Big heart on chest X-Ray.
•Patient comes with heart failure.
1. Hypertrophic (< 10%)
2. Restrictive (< 2%)
•Least common.
Classification
• Etiology- primary or • immunology
secondary • hemodynamics
• gross anatomy • functional
• histology • prognosis
• genetics • treatment
• biochemistry
 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

100 104

80
72
60 56
51
45
40 37 35 31
20 24
19 16
0
0 1 2 3 4 5 6 7 8 9 10
Years
Am J Cardiol 1981; 47:525
Predicting Prognosis in IDC
Predictive Possible Not Predictive
Clinical factors symptoms alcoholism age
peripartum duration
family history viral illness
Hemodynamics LVEF LV size
Cardiac index atrial pressure
Dysarrhythmia LV cond delay AV block simple VPC
complex VPC atrial fibrillation
Histology myofibril volume other findings
Neuroendocrine 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 ß-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
whereConcentric
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 Feature

I Hypertrophy confined to Anterior

segment of the IVS
II Hypertrophy confined to Anterior and
Inferior segments of the IVS
III Extensive hypertrophy of LV with
sparing of the basal segment of the
posterior wall.
IV Apical hypertrophy
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 Fixed Obstruction

carotid pulse spike and dome parvus et tardus

murmur radiate to carotids
 valsalva, standing
 squatting, handgrip
 passive leg elevation
systolic thrill 4th left interspace 2nd right interspace
systolic click absent present
Other Causes of Hypertrophy
• Clinical mimics
• glycogen storage, infants of diabetic mothers, amyloid
• Genetic
• Noonan’s, Friedreich’s ataxia, Familial restrictive
cardiomyopathy with disarray
• Exaggerated physiologic response
• Afro-Caribbean hypertension, old age hypertrophy,
athlete’s heart
HCM vs Athlete’s Heart
HCM Athlete
+ 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

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
cardiomyopath
y:
Biatrial
dilatation,
grossly normal
ventricles
Classification
• Idiopathic 3. Storage Disease
• Myocardial • Hemochromatosis
1. Noninfiltrative • Fabry disease
• Idiopathic • Glycogen storage
• Scleroderma • Endomyocardial
2. Infiltrative • endomyocardial fibrosis
• Amyloid • Hyperesinophilic synd
• Sarcoid • Carcinoid
• Gaucher disease • metastatic malignancies
• Hurler disease • 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)