Download Myocardium 2013

The Pathology of
Myocardial
Diseases
(1) Cardiomyopathy
– Defined as “heart muscle disease of
unknown cause,” generally referred to as
primary or idiopathic cardiomyopathy,
(2) Specific heart muscle disease
– defined as “heart muscle disease of
known cause or associated with disorders
of other systems.
Myocardium
Cardiomyopathies
The clinical picture is largely
determined by one of the
following three clinical,
functional, pathologic patterns,
each of which can have either a
known or an unknown cause:
Dilated Cardiomyopathy (90%)
Hypertrophic Cardiomyopathy
Restrictive Cardiomyopathy
Myocardium
Dilated Cardiomyopathy
(DCM)
Etiology of the DCM :
– 1. Primary (Idiopathic) (30%) DCM
– 2. Secondary DCM
Myocardium
1. Primary (Idiopathic) dilated
cardiomyopathy
Characterized by the gradual development of cardiac
failure associated with four-chamber hypertrophy
and dilatation of the heart of unknown cause.
Familial occurrence (approximately 20% of cases)
– autosomal dominant, autosomal recessive, and X-linked
inheritance
Genetic syndromes:
– Friedreich's ataxia
– Duchenne's-Becker's muscular dystrophy
Myocardium
Pathophysiology
Apoptosis, or programmed cell death, has
been reported in clinical and experimental
dilated cardiomyopathy, which is characterized
by
– depressed systolic function or systolic pump failure
– cardiomegaly
– ventricular dilatation
Reduced left ventricular contractile force leads
to decreased cardiac output, resulting in
increased residual volumes in end-systole and
end-diastole.
Myocardium
Usually affects those 20 to 60 years old
Slowly develops
Fifty percent of patients die within 2 years
– only 25% of patients survive longer than 5 years
Death is usually attributable to
– progressive cardiac failure and/or
– arrhythmia
Embolism from dislodgement of an
intracardiac thrombus may occur
Myocardium
Secondary dilated cardiomyopathies
– Alcoholism
– Chemicals&Drugs
Heavy metals
Emetine
Doxorubicin
Cocaine
Methamphetamine
Cobalt
– High output states
Anemia
Thyrotoxicosis
Pregnancy
– HIV and other infections
Viral
endocarditis/myocarditis
Parasites
Protozoa
Chagas disease (most
common cause in parts of
South America)
– Collagen vascular disease
– Glycogen storage disease
– Thiamine deficiency and
zinc deficiency
– Hypophosphatemia
– Amyloidosis
– Neuromuscular disorders
Myocardium
Pathology
The heart is usually heavy
– Weighing two to three times normal,
– Flabby (usually with dilatation of all chambers)
Nevertheless, because of the wall thinning that
accompanies dilatation, the ventricular wall
thickness may be less than, equal to, or more
than normal.
Mural thrombi are common
– particularly near the apex of the left and right
ventricles and in the atria  thromboembolism
Mitral regurgitation, when present, is primarily
a result of left ventricular chamber dilatation
(functional mitral regurgitation).
Myocardium
The left ventricle often has patchy
myocardial (mostly subendocardial)
fibrous scars
The sizes of individual muscle cells vary;
The nuclei are usually enlarged
throughout, indicating hypertrophy.
Myocardium
Complications
– Heart failure
– Volume overload
– Pulmonary edema
– Hypoxia
– Cardiogenic shock
– Death
Myocardium
Arrhythmogenic Right Ventricular
Cardiomyopathy
(Right ventricular Dysplasia)
Familial disorder
Progressive nature of the lesion with apoptosis
Sudden death in vigorous good health
– right-sided and sometimes left-sided heart failure
– rhythm disturbances (particularly ventricular tachycardia)
Morphology
– the right ventricular wall is severely thinned,
extensive fatty infiltration
loss of myocytes
interstitial fibrosis
Myocardium
Hypertrophic Cardiomyopathy (HCM)
Hypertrophic cardiomyopathy is also known by
such terms as
Synonyms:
–
–
–
–
–
idiopathic septal hypertrophy
asymmetric septal hypertrophy
Les Aspin's disease
Reggie Lewis's disease
muscle-bound heart
A genetic basis in many cases
Myocardium
It is characterized by a heavy muscular
hypercontracting heart, in striking contrast
to the flabby, hypocontracting heart of
dilated CM.
In contrast to the hypertrophy induced by
the increased workload of valvular,
hypertensive, ischemic, and congenital
heart diseases, that observed in
Hypertrophic CM develops progressively
in the absence of an identifiable extrinsic
inciting stress.
Myocardium
End-stage heart failure can be
accompanied by dilatation.
The major problems in HCM are:
– atrial fibrillation with mural thrombus formation,
– embolization from the mural thrombi,
– infective endocarditis on the mitral valve,
– intractable cardiac failure,
– sudden death (most common cause of death
and particularly likely in young males with
familial HCM or with a family history of sudden
death).
Myocardium
Morphological findings
The essential anatomic feature of HCM is
massive myocardial hypertrophy.
The classic pattern is said to be
disproportionate thickening of the ventricular
septum as compared with the free wall of the
left ventricle (with a ratio greater than 1.3),
frequently termed asymmetric septal
hypertrophy.
Myocardium
Restrictive Cardiomyopathy
(RCM)
Restrictive cardiomyopathy can be
idiopathic or secondary to a heart muscle
disease that manifests as restrictive
physiology.
The common hemodynamic disturbance is
impairment of ventricular filling due to the
thickening and increased rigidity of the
endocardium and myocardium secondary
to infiltration by amyloid or by fibrosis.
Myocardium
Systolic function remains normal or near
normal until late stages.
Most older people get some amyloid in
their atria and aortas.
If amyloid involves the myocardium
extensively, the muscles cannot contract.
This is the usual cause of "restrictive
cardiomyopathy".
Myocardium
Etiology:
– Idiopathic restrictive cardiomyopathy
Loeffler eosinophilic endomyocardial disease
– Secondary restrictive cardiomyopathy
Hemochromatosis
Amyloidosis
Sarcoidosis
Progressive systemic sclerosis (scleroderma)
Carcinoid heart disease
Glycogen storage disease of the heart
Myocardium
MORPHOLOGY:
– the ventricles are of approximately normal
size or slightly enlarged
– the cavities are not dilated
– the myocardium is firm
– biatrial dilatation (common)
Microscopically there is patchy or diffuse
interstitial fibrosis/amyloid.
Myocardium
Specific Heart Muscle
Disease
Cardiac infections
Viruses
–
–
–
–
–
coxsackievirus
ECHO
influenza
HIV
CMV
Chlamydia (C.psitacci)
Rickettsia
Bacteria
– Corynebacterium
– Neisseria
– Borrelia
Fungi (Candida)
Protozoa
– Trypanosoma
– Toxoplasma
Helminth (Trichinosis)
Myocardium
Toxic substances
Alcohol
Cobalt
Cathecolamines
CO
Lithium
Hydrocarbons
Arsenic
Cancer chemotherapy
Myocardium
Metabolic causes
Hyperthyroidism
Hypothyroidism
Hypokalemia
Hyperkalemia
Hypoproteniamia,
Hypovitaminosis(thiamin
e)
Hemochromatosis
Myocardium
Neuromuscular
disease
Friedreichs ataxia
Muscular dystrophia
Congenital atrophies
Stroge disorders
Hunter-Hurler syndrome
Glycogen storage
disease
Amyloidosis
Myocardium
Infiltrative
diseases
Leukemia
Carcinomatosis
Sarcoidosis
Radiation-induced fibrosis
Immun-mediated
reactions
Myocarditis
Post-transplant rejection
Myocardium
Myocarditis
Myocarditis is an uncommon disease that
is characterized by inflammation of the
heart;
– leukocytic infiltrate
– resultant nonischemic necrosis
– degeneration of myocytes
Subsequent myocardial destruction often
leads to a dilated cardiomyopathy.
Most cases of well-documented
myocarditis are viral in origin.
Myocardium
Etiology of Myocarditis
Infectious
agents
- Viruses (Coxsackievirus(B), Advenovirus,
Echovirus, EBV, Hepatitis C, HHV, HIV, CMV,
Influenza, Measles, Mumps, Rubella, Varicella)
- Chlamydia (C.psitacci)
- Rickettsia (R. rickettsii, R. tsutsugamushi)
- Bacteria (Corynebacterium, Neisseria, Borrelia,
Klebsiella, Leprospira, Cocci, Clostridia,
Treponema, Brucella, Salmonella)
- Fungi (Candida, Actinomycosis,
Coccidioidomycosis, Histoplasmosis)
- Protozoa (Trypanosoma cruzi, toxoplasma,
amebiasis)
- Other parasites (Toxocara canis,
Schistosomiasis, Heterophyiasis, Cysticercosis,
Echinococci, Visceral larva migrans.
Myocardium
Immun-mediated
reactions
- Post-transplant rejection
- Medications
Drugs
– Hypersensitivity myocarditis is
observed with a variety of
medications (eosinophilic infiltrate
of the myocardium)
– A direct cytotoxic effect on the
myocardium
- penicillin, ampicillin,
hydrochlorothiazide, methyldopa,
sulfonamide
- lithium, doxorubicin, cocaine,
numerous catecholamines,
acetaminophen,
cyclophosphamide, tetracycline,
isoniazid, phenytoin, ect.
Myocardium
Chemicals
Systemic diseases
Lead
Arsenic
Carbon monoxide
Scorpion envenomations
Autoimmune diseases ( SLE,
Scleroderma, Rhematoid arthritis)
Sarcoidosis
Giant cell myocarditis
SLE
Giant cell arteritis
Dermatomyositis
Ulcerative colitis
Radiation therapy
(dilated cardiomyopathy)
Myocardium
It may occur at any age
The vulnerable ones...
– infants
– immunosuppressed individuals
– pregnant women
Myocardium
A Specific type of Myocarditis: Chagas’
disease
Caused by a protozoa: Trypanosoma cruzi
Although uncommon in the northern
hemisphere, Chagas’ disease affects up to onehalf of the population in endemic areas of South
America.
Myocardial involvement is found in
approximately 80% of infected individuals.
Myocardium
Trichinosis
The most common helminthic disease with
associated cardiac involvement.
Corynebacterium diphtheriae
Traditionally considered a myocarditis, injury to
the myocardium by the potent exotoxin of the
bacterium Corynebacterium diphtheriae is
characterized by patchy myocyte necrosis with
only a sparse lymphocytic infiltrate.
Myocardium
HIV myocarditis
Myocarditis occurs in many patients with
acquired immunodeficiency syndrome
(AIDS).
Two types have been identified:
– (1) inflammation and myocyte damage without
a clear etiologic agent
– (2) myocarditis caused directly by HIV or by
an opportunistic pathogen
Myocardium
Morphology
During the active phase of myocarditis, the
heart may appear normal or enlarged with
dilatation of either ventricle or all chambers.
The lesions may be diffuse or patchy.
The ventricular myocardium is typically
flabby and often mottled by either pale foci
or minute hemorrhagic lesions.
The endocardium and valves are
unaffected except that mural thrombi may
be present in any chamber.
Myocardium
Microscopic classification:
Nonmyocarditis
Active myocarditis
– Characterized by abundant inflammatory cells
and myocardial necrosis
Borderline myocarditis
– Characterized by an inflammatory response
that is too sparse for this type to be labeled as
active myocarditis; degeneration of myocytes
not demonstrated with light microscopy.
Myocardium
Histology
During Active myocarditis
Interstitial mononuclear, predominantly
lymphocytic inflammatory infiltrate (focal
or patchy) +
Focal necrosis
necrosis and disarrangement of the
myocytes are typical and often are seen
with coxsackievirus infection
occasionally with a necrotic myocyte
(often with contraction bands)
Myocardium
The histologic pattern of reaction to bacterial or
fungal invasion depends on the specific
causative organism, if present.
Hypersensitivity reactions that involve the
myocardium induce interstitial infiltrates that are
principally perivascular, composed of
lymphocytes, macrophages, and a high
proportion of eosinophils.
In the chronic and healing stages, myocytes are
replaced by fibroblasts (scar tissue).
Myocardium
– In giant cell myocarditis, giant cells are
present in the myocardium with or without
granulomas.
Tuberculosis, syphilis, rheumatoid arthritis,
rheumatic heart disease, or with fungal or
parasitic infections.
The characteristic cell probably is histiocytic in
origin and usually is found in nonviral
myocarditis.
Similar cells have been noted in patients with
myocarditis associated with drugs such as
phenylbutazone.
Myocardium
– Systemic lupus erythematosus (SLE) may
demonstrate myocardial fibrinoid lesions
found in the connective tissue with an
accompanying cellular reaction.
This reaction also may affect the valves, most
notably, the mitral and aortic valves.
Libman and Sacks describe this latter type of
endocarditis.
Although the predominant cardiac manifestation
of SLE is pericarditis, myocardial involvement
with CHF can occur
Myocardium
Viral Myocarditis
Myocardium
Aspergillus Myocarditis
Myocardium
Pyemic Myocarditis
Myocardium
Complications:
– Congestive heart failure
– Pulmonary edema
– Cardiogenic shock
– Cardiac failure
– Recurrent myositis
– Dysrhythmia/Arrhythmia
– Thromboembolism.
Myocardium
Secondary cardiomyopathies
Alcohol
Chemotherapy (doxo- and daunorubicin; Adriamycin)
Cathecolamines and Pheochromocytoma
("catecholamine heart", with single-fiber necrosis as
in cocaine heart)
Peripartum cardiomyopathy
Amyloidosis
Hemochromatosis
Hyper-/hypo- thyroidism
Pompe's glycogenosis
Duchenne's & Friedreich's Disease
Myocardium
End-stage HIV infection
Alcohol
Alcohol or its metabolites (especially acetaldehyde)
has a direct toxic effect on the myocardium
Chronic alcoholism may be associated with
thiamine deficiency, introducing an element of
beriberi heart disease
Adriamycin and Other Drugs
Some of the chemotherapeutic agents doxorubicin
(adriamycin) and daunorubicin are well recognized
causes of toxic myocardial injury
Many other agents, such as lithium,
phenothiazines, and cocaine, have been implicated
in myocardial injury
Cocaine also causes catecholamine-induced cell
damage
Myocardium
Peripartum cardiomyopathy
Pregnancy invokes the possibilities of
– hypertension
– volume overload
– nutritional deficiency
– other metabolic derangement
– immunologic reaction
Myocardium
Amyloidosis
Cardiac amyloidosis may appear along
with systemic amyloidosis or may affect
only the heart, particularly in the aged
(senile isolated cardiac amyloidosis)
Clinically important amyloid deposits can
occur in the hearts of patients with multiple
myeloma
Myocardium
Hereditary hemochromatosis and
hemosiderosis
Most commonly with a dilated pattern
Iron deposition is more prominent in
ventricles than atria and in the working
myocardium than in the conduction
system
Microscopy
– marked accumulation of hemosiderin within
cardiac myocytes (intracellular)
– Varying degrees of cellular degeneration and
fibrosis
Myocardium
THANK YOU
Myocardium