Myocardial and Pericardial Disease, cardiac tumors

1
Myocardial and Pericardial Disease, cardiac
tumors

• Anjali Shinde, MD
• Mount Sinai Hospital
• Chicago

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Outline

• Cardiomyopathy
• Dilated
• Hypertrophic
• Restrictive
• Myocarditis
• Other causes of myocardial disease
• Pericardial disease
• Pericardial effusion and hemopericardium
• Pericarditis-
• Acute
• -Serous
• -Fibrinous and serofibrinous
• -Purulent/suppurative
• -Hemorrhagic
• -Caseous
• Chronic/ healed
• Heart disease with Rheumatoid disease
• Cardiac tumors
• Cardiac effects of non cardiac neoplasm

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Cardiomyopathy

• Cardiomyopathy - heart disease resulting from an
  abnormality in the myocardium
• Diseases of the myocardium usually produce
  abnormalities in cardiac wall thickness and
  chamber size, and mechanical and/or electrical
  dysfunction
• Primary cardiomyopathies- predominantly confined
  to the heart muscle
• Secondary cardiomyopathies - myocardial
  involvement as a component of a systemic or
  multiorgan disorder

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Conditions Associated with Heart Muscle Diseases

• cardiac infections
• VirusesChlamydiaRickettsiaBacteriaFungiProto
  zoa
• toxins
• AlcoholCobaltCatecholaminesCarbon
  monoxideLithiumHydrocarbonsArsenicCyclophospha
  mideDoxorubicin (Adriamycin) and daunorubicin
• metabolic
• HyperthroidismHypothyroidismHyperkalemiaHypoka
  lemiaNutritional deficiency (protein, thiamine,
  other avitaminoses)Hemochromatosis

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Cardiomyopathy
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Conditions Associated with Heart Muscle Diseases

• neuromuscular disease
• Friedreich ataxiaMuscular
  dystrophyCongenital atrophies
• storage disorders and other depositions
• Hunter-Hurler syndromeGlycogen storage
  diseaseFabry diseaseAmyloidosis
• infiltrative
• LeukemiaCarcinomatosisSarcoidosisRadiation-in
  duced fibrosis
• immunological
• Myocarditis (several forms)Post-transplant
  rejection

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Cardiomyopathy

• Cardiomyopathies of diverse etiology may have a
  similar morphologic appearance
• Clinical approach is largely determined by which
  of three clinical, functional, and pathologic
  patterns is present
• dilated cardiomyopathy (DCM),
• hypertrophic cardiomyopathy (HCM),
• restrictive cardiomyopathy
• Another rare form of cardiomyopathy, left
  ventricular noncompaction, is characterized by a
  distinctive "spongy" appearance of the left
  ventricular myocardium. This congenital disorder
  is frequently associated with heart failure or
  arrhythmias and other clinical symptomatology it
  may be diagnosed in children or adults as either
  an isolated finding or associated with other
  diseases

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Table 12-10
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DILATED CARDIOMYOPATHY

• Dilated cardiomyopathy/congestive cardiomyopathy
  (DCM)-characterized by progressive cardiac
  dilation and contractile (systolic) dysfunction,
  usually with concomitant hypertrophy.
• Heart is usually enlarged, heavy (often weighing
  two to three times normal), and flabby due to
  dilation of all chambers
• Mural thrombi are common and may be a source of
  thromboemboli
• No primary valvular alterations.
• Regurgitation, when present, results from
  ventricular chamber dilation (functional
  regurgitation)

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DILATED CARDIOMYOPATHY
Normal heart
A, Four-chamber dilatation and hypertrophy B,
Histologic section demonstrating variable myocyte
hypertrophy and interstitial fibrosis (collagen
is highlighted as blue with Masson trichrome
stain). The histologic abnormalities in DCM are
nonspecific
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PATHOGENESIS OF DILATED CARDIOMYOPATHY (DCM)

• Genetic influences In 20 to 50 of cases, DCM
  is familial and caused by inherited genetic
  abnormalities.
• Autosomal-dominant inheritance is the predominant
  pattern
• Most commonly affected genes are those that
  encode cytoskeletal proteins expressed by
  myocytes
• Mitochondrial defects most frequently cause
  dilated cardiomyopathy in children.
• X-linked dilated cardiomyopathy typically
  presents in the teenage years or in the early 20s
  and is usually rapidly progressive. Associated
  with mutations in the gene that encodes
  dystrophin
• Some patients and families with dystrophin gene
  mutations have DCM as the primary clinical
  feature.
• Mutations in genes encoding cardiac a-actin
  (which links the sarcomere with dystrophin),
  desmin, and the nuclear lamina proteins, lamin A
  and lamin C can also cause DCM

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Pathogenesis of dilated cardiomyopathy

• Peripartum cardiomyopathy
• Can occur late in pregnancy or several weeks to
  months postpartum.
• Probably multifactorial.
• Pregnancy-associated hypertension, volume
  overload, nutritional deficiency, other metabolic
  derangements, or an as yet poorly characterized
  immunological reaction have been proposed as
  causes.
• Recent work suggests a relationship between
  elevated levels of an anti-angiogenic cleavage
  product of the hormone prolactin (which rises
  late in pregnancy) and peripartum cardiomyopathy.
  

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Pathogenesis of dilated cardiomyopathy

• Alcohol and other toxins.
• Alcohol abuse is strongly associated with the
  development of DCM, raising the possibility that
  ethanol toxicity or a secondary nutritional
  disturbance may be the cause of the myocardial
  injury.
• Alcohol or its metabolites (especially
  acetaldehyde) have a direct toxic effect on the
  myocardium
• Chronic alcoholism may be associated with
  thiamine deficiency, which can lead to beriberi
  heart disease (also indistinguishable from DCM)
• Certain chemotherapeutic agents, including
  doxorubicin (Adriamycin) can also cause
  cardiomyopathy

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Pathogenesis of dilated cardiomyopathy

• Myocarditis
• Clinical studies using sequential endomyocardial
  biopsies have demonstrated progression from
  myocarditis to DCM
• Viral nucleic acids from coxsackievirus B and
  other enteroviruses have been detected in the
  myocardium of patients with DCM suggesting that
  in some cases, DCM is a consequence of myocarditis

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Clinical features

• DCM may occur at any age commonly affects
  individuals between the ages of 20 and 50
• Presents with slowly progressive signs and
  symptoms of congestive heart failure such as
  shortness of breath, easy fatigability, and poor
  exertional capacity.
• End stage patients often have ejection fractions
  of less than 25 (normal 50 to 65)
• Fifty percent of patients die within 2 years, and
  only 25 survive longer than 5 years, but some
  severely affected patients may unexpectedly
  improve on therapy.
• Secondary mitral regurgitation and abnormal
  cardiac rhythms are common.
• Death is usually attributable to progressive
  cardiac failure or arrhythmia and can occur
  suddenly.
• Cardiac transplantation is frequently done, and
  long-term ventricular assist may be helpful

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Arrhythmogenic Right Ventricular Cardiomyopathy

• Synonym Arrhythmogenic Right Ventricular
  Dysplasia
• Inherited disease of the cardiac muscle
• Causes right ventricular failure and various
  rhythm disturbances, particularly ventricular
  tachycardia or fibrillation
• Can lead to sudden death, primarily in young
  people.
• Left-sided involvement with left-sided heart
  failure may also occur.
• Morphologically, the right ventricular wall is
  severely thinned because of loss of myocytes,
  with extensive fatty infiltration and fibrosis
• Autosomal-dominant inheritance and variable
  penetrance. The disease seems to be related to
  defective cell adhesion proteins in the
  desmosomes that link adjacent cardiac myocytes.
• Naxos syndrome -disorder characterized by
  arrhythmogenic right ventricular cardiomyopathy
  and hyperkeratosis of plantar palmar skin surfaces

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Arrhythmogenic Right Ventricular Cardiomyopathy
A, Gross photograph, showing dilation of the
right ventricle and near-transmural replacement
of the right ventricular free-wall by fat and
fibrosis. The left ventricle has a virtually
normal configuration. B Histologic section of
the right ventricular free wall, demonstrating
replacement of myocardium (red) by fibrosis
(blue, arrow) and fat (Masson trichrome stain).
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HYPERTROPHIC CARDIOMYOPATHY

• Hypertrophic cardiomyopathy (HCM) - characterized
  by myocardial hypertrophy, poorly compliant left
  ventricular myocardium leading to abnormal
  diastolic filling, and in about one third of
  cases, intermittent ventricular outflow
  obstruction.
• Leading cause of left ventricular hypertrophy
  which is unexplained by other clinical or
  pathologic causes.
• HCM caused by mutations in genes encoding
  sarcomeric proteins
• Heart is thick-walled, heavy, and
  hypercontracting, in striking contrast to the
  flabby, hypocontracting heart of DCM. HCM causes
  primarily diastolic dysfunction systolic
  function is usually preserved
• Two most common diseases that must be
  distinguished clinically from HCM are deposition
  diseases of the heart (e.g., amyloidosis, Fabry's
  disease) and hypertensive heart disease coupled
  with age-related subaortic septal hypertrophy

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HYPERTROPHIC CARDIOMYOPATHY

• Morphology Massive myocardial hypertrophy,
  usually without ventricular dilation
• Classic pattern is disproportionate ventricular
  septal wall thickening compared with the free
  wall of the left ventricle (with a ratio greater
  than 1 3), frequently termed asymmetric septal
  hypertrophy..
• On cross-section, the ventricular cavity may be
  compressed into a "banana-like" configuration by
  bulging of the ventricular septum into the lumen
• Although marked hypertrophy can involve the
  entire septum, it is usually most prominent in
  the subaortic region
• The most important histologic features are
• (1) extensive myocyte hypertrophy to a degree
  unusual in other conditions, with transverse
  myocyte diameters frequently greater than 40 µm
  (normal, 15 µm)
• (2) haphazard disarray of bundles of myocytes,
  individual myocytes, and contractile elements in
  sarcomeres within cells (termed myofiber
  disarray) and
• (3) interstitial and replacement fibrosis

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HYPERTROPHIC CARDIOMYOPATHY
B, Histologic appearance demonstrating disarray,
extreme hypertrophy, and branching of myocytes
Hypertrophic cardiomyopathy with asymmetric
septal hypertrophy. A, The septal muscle bulges
into the left ventricular outflow tract, and the
left atrium is enlarged.
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pathogenesis

• HCM - caused by missense mutations in genes that
  encode sarcomeric proteins.
• Autosomal dominant, some cases sporadic
• Mutations in myosin heavy chain ß-MHC, myosin
  binding protein MYBP-C and cardiac TnT account
  for 70 to 80 of all cases of HCM.
• Prognosis of HCM varies widely and correlates
  strongly with specific mutations
• Sequence of events leading from mutations to
  disease is still poorly understood.

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Clinical features of hcm

• Basic physiologic abnormality in HCM is reduced
  stroke volume due to impaired diastolic filling,
  which results from the reduced chamber size and
  compliance of the massively hypertrophied left
  ventricle.
• Harsh systolic ejection murmur is present- caused
  by ventricular outflow obstruction as the
  anterior mitral leaflet moves toward the
  ventricular septum during systole
• Because of the massive hypertrophy, high left
  ventricular chamber pressure, and frequently
  abnormal intramural arteries, focal myocardial
  ischemia and anginal pain is frequent

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Clinical features of hcm

• Atrial fibrillation, mural thrombus formation
  leading to embolization and possible stroke,
  intractable cardiac failure, ventricular
  arrhythmias, and, not infrequently, sudden death,
  especially in some affected families.
• HCM is one of the most common causes of sudden,
  otherwise unexplained death in young athletes
• Patients treated with drugs that decrease heart
  rate and contractility, such as ß-adrenergic
  blockers.
• Surgical reduction of the mass of the septum

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RESTRICTIVE CARDIOMYOPATHY

• Restrictive cardiomyopathy is a disorder
  characterized by a primary decrease in
  ventricular compliance, resulting in impaired
  ventricular filling during diastole
• Restrictive cardiomyopathy may be idiopathic or
  associated with distinct diseases or processes
  that affect the myocardium, principally radiation
  fibrosis, amyloidosis, sarcoidosis, metastatic
  tumors, or the deposition of metabolites that
  accumulate due to inborn errors of metabolism.

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Restrictive cardiomyopathy- morphology

• The ventricles are of approximately normal size
  or slightly enlarged, the cavities are not
  dilated, but the myocardium is firm and
  noncompliant.
• Biatrial dilation is commonly observed.
  Microscopically, there may be patchy or diffuse
  interstitial fibrosis
• Other restrictive conditions-
• Endomyocardial fibrosis-disease of children and
  young adults in Africa and other tropical areas
  fibrosis of the ventricular endocardium and
  subendocardium extending from the apex upward,
  involving tricuspid and mitral valves. Volume
  diminished and compliance affected

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Restrictive cardiomyopathyrestrictive conditions

• Loeffler endomyocarditis -
• Endomyocardial fibrosis, typically with large
  mural thrombi, peripheral eosinophilia and
  eosinophilic infiltrates in other organs.
• Eosinophils release major basic protein which is
  postulated to initiate endomyocardial necrosis,
  scarring of the necrotic area, thrombus formation
  and reorganization.
• Some patients have a myeloproliferative disorder
  associated with fusion genes PDGFR tyrosine
  kinase. Treatment is with tyrosine kinase
  inhibitor imatinib which causes reversal of
  disease (otherwise fatal)
• Endocardial fibroelastosis-
• Uncommon heart disease of obscure etiology
  characterized by focal or diffuse fibroelastic
  thickening usually involving the mural left
  ventricular endocardium.
• Most common in the first 2 years of life
• Diffuse involvement may be responsible for rapid
  and progressive cardiac decompensation and death

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Myocarditis
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Myocarditis- Etiology

• Viruses (coxsackievirus, ECHO, influenza, HIV,
  cytomegalovirus) are the most common cause of
  myocarditis in US. Coxsackieviruses A and B and
  other enteroviruses probably account for most of
  the cases
• Trypanosoma cruzi, agent of Chagas disease
• Myocarditis occurs in approximately 5 of
  patients with Lyme disease caused by the
  bacterial spirochete Borrelia burgdorferi. Lyme
  myocarditis manifests primarily as a self-limited
  conduction system disorder that frequently
  requires a temporary pacemaker
• AIDS- (1) inflammation and myocyte damage without
  a clear etiologic agent and (2) myocarditis
  caused by HIV directly or by an opportunistic
  pathogen
• Hypersensitivity reactions (hypersensitivity
  myocarditis), often to drugs such as antibiotics,
  diuretics, or antihypertensive agents.
• Rheumatic fever, systemic lupus erythematosus,
  and polymyositis
• Cardiac sarcoidosis and rejection of a
  transplanted heart are also considered forms of
  myocarditis.
• .

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Morphology of myocarditis

• Active phase of myocarditis the heart may appear
  normal or dilated. An interstitial inflammatory
  infiltrate is seen
• In advanced stages the ventricular myocardium is
  flabby and often mottled by either pale foci or
  minute hemorrhagic lesions. Mural thrombi may be
  present in any chamber
• Hypersensitivity myocarditis has interstitial
  infiltrates, principally perivascular, composed
  of lymphocytes, macrophages, and a high
  proportion of eosinophils
• Giant-cell myocarditis- characterized by a
  widespread inflammatory cellular infiltrate
  containing multinucleate giant cells interspersed
  with lymphocytes, eosinophils, plasma cells, and
  macrophages. Focal to frequently extensive
  necrosis. Poor prognosis.
• Chagas disease - parasitization of scattered
  myofibers by trypanosomes accompanied by an
  inflammatory infiltrate of neutrophils,
  lymphocytes, macrophages, and occasional
  eosinophils.
• Clinical spectrum of myocarditis is broad-
  entirely asymptomatic or at the other extreme,
  precipitous onset of heart failure or
  arrhythmias, occasionally with sudden death
• Patients haves symptoms such as fatigue,
  dyspnea, palpitations, precordial discomfort, and
  fever. The clinical features of myocarditis can
  mimic those of acute MI. Occasionally, patients
  develop dilated cardiomyopathy as a late
  complication of myocarditis.

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Myocarditis. A, Lymphocytic myocarditis,
associated with myocyte injury. B,
Hypersensitivity myocarditis, characterized by
interstitial inflammatory infiltrate composed
largely of eosinophils and mononuclear
inflammatory cells, predominantly localized to
perivascular and expanded interstitial spaces. C,
Giant-cell myocarditis, with mononuclear
inflammatory infiltrate containing lymphocytes
and macrophages, extensive loss of muscle, and
multinucleated giant cells. D, The myocarditis of
Chagas disease. A myofiber distended with
trypanosomes (arrow) is present along with
inflammation and necrosis of individual myofibers
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OTHER CAUSES OF MYOCARDIAL DISEASE

• Cardiotoxic Drugs Cardiotoxicity can be
  associated with conventional chemotherapeutic
  agents, targeted drugs such as tyrosine kinase
  inhibitors, and certain forms of immunotherapy.
• Anthracyclines, doxorubicin and daunorubicin -
  chemotherapeutic agents most often associated
  with toxic myocardial injury, leading to dilated
  cardiomyopathy and heart failure
• Anthracycline toxicity is dose-dependent
• Lithium, phenothiazines, chloroquine, and
  cocaine, have been implicated in myocardial
  injury and sometimes sudden death

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Cardiac effects of catecholamines

• Seen in patients with pheochromocytoma, autonomic
  stimulation, or large doses of vasopressor agents
• Sudden, intense emotional or physical stress can
  also induce acute left ventricular dysfunction
  due to myocardial stunning, a phenomenon known as
  Takotsubo cardiomyopathy
• Histology- Foci of myocardial necrosis with
  contraction bands and few macrophages

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amyloid

• Amyloidosis- caused by deposition insoluble
  extracellular fibrillar deposits of protein
  fragments that are prone to forming ß-pleated
  sheets.
• Cardiac amyloidosis may appear along with
  systemic amyloidosis or be restricted to the
  heart, particularly in the aged (senile cardiac
  amyloidosis)
• In senile cardiac amyloidosis, amyloid deposits
  occur in the ventricles and atria- caused by the
  deposition of transthyretin.
• Senile cardiac amyloidosis has better prognosis
  than systemic amyloidosis
• Cardiac amyloidosis most frequently produces a
  restrictive cardiomyopathy, but it can also be
  asymptomatic or manifest as dilation,
  arrhythmias, or symptoms mimicking those of
  ischemic or valvular disease

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amyloid

• Morphology
• Heart varies in consistency from normal to firm
  and rubbery
• Numerous small, semitranslucent nodules
  resembling drips of wax may be seen at the atrial
  endocardial surface
• Eosinophilic deposits of amyloid may be found in
  the interstitium, conduction tissue, valves,
  endocardium, pericardium, and small intramural
  coronary
• Amyloid can be regognized by Congo red, which
  produces classic apple-green birefringence when
  viewed under polarized light

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Cardiac amyloidosis
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Cardiac effects in iron overload

• Either hereditary hemochromatosis or multiple
  blood transfusions (hemosiderosis)
• Heart is usually dilated
• Iron deposition is more prominent in ventricles
  and in the myocardium.
• Morphology. Grossly, the myocardium of the
  iron-overloaded heart is rust-brown in color
  Microscopically, there is marked accumulation of
  hemosiderin within cardiac myocytes, particularly
  in the perinuclear region, demonstrable with a
  Prussian blue stain and is associated with
  varying degrees of cellular degeneration and
  fibrosis.

Prussian blue stain
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Cardiac effects in thyroid disease

• Hyperthyroidism and Hypothyroidism
• Hyperthyroidism-tachycardia, palpitations, and
  cardiomegaly are common supraventricular
  arrhythmias occasionally appear. Cardiac failure
  is uncommon gross and histologic features are
  those of nonspecific hypertrophy and can also
  include ischemic foci.
• Hypothyroidism- cardiac output is decreased, due
  to reductions in stroke volume and heart rate.
  Increased peripheral vascular resistance and
  decreased blood volume In well-advanced
  hypothyroidism (myxedema) heart is flabby,
  enlarged, and dilated.
• Histologic features of hypothyroidism include
  myofiber swelling with loss of striations and
  basophilic degeneration, accompanied by
  interstitial mucopolysaccharide-rich edema fluid.
  
• A similar fluid sometimes accumulates within the
  pericardial sac- myxedema heart

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Pericardial disease

• Pericardial disorders occur usually in
  association with disease elsewhere in the heart
  or other systems
• Isolated pericardial disease is unusual
• Pericardial disease causes fluid accumulation,
  inflammation or fibrous constriction

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Pericardial disease
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PERICARDIAL EFFUSION AND HEMOPERICARDIUM

• Normally pericardial fluid is- 30 to 50 mL, thin,
  clear and straw-colored
• Under various circumstances the parietal
  pericardium may be distended by serous fluid
  (pericardial effusion), blood (hemopericardium),
  or pus (purulent pericarditis).
• With long-standing pressure or volume overload,
  the pericardium dilates-allowing a slowly
  accumulating pericardial effusion to become quite
  large without interfering with cardiac function.
• Chronic effusions of less than 500 mL in volume
  cause little clinical significance except a
  characteristic globular enlargement of the heart
  shadow on chest radiographs.
• Rapidly developing fluid collections of as little
  as 200 to 300 mL due to hemopericardium caused by
  a ruptured MI or aortic dissection-may produce
  compression of the thin-walled atria, venae
  cavae, or ventricles producing potentially fatal
  cardiac tamponade.

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PERICARDITIS-etiology

• infectious agents
• Viruses- commonest cause of primary
  pericarditisPyogenic becteriaTuberculosisFungi
  Other parasites
• presumably immunologically mediated
• Rheumatic feverSystemic lupus
  erythematosusSclerodermaPostcardiotomyPostmyoca
  rdial infarction (Dressler) syndromeDrug
  hypersensitivity reaction
• Miscellaneous
• Myocardial infarctionUremiaFollowing cardiac
  surgeryNeoplasiaTraumaRadiation
• Pericardial inflammation may occur secondary to a
  variety of cardiac diseases, thoracic or systemic
  disorders, metastases from neoplasms arising in
  remote sites, or a surgical procedure on the
  heart.

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Acute Pericarditis

• 1. Serous Pericarditis
• Characteristically produced by noninfectious
  inflammatory diseases- rheumatic fever, SLE,
  scleroderma, tumors, and uremia.
• Infection in the tissues contiguous to the
  pericardium-for example, a bacterial pleuritis
  can lead to irritation of the parietal
  pericardial serosa to cause a sterile serous
  effusion
• Viral infection elsewhere-upper respiratory tract
  infection, pneumonia, parotitis-antedates the
  pericarditis and serves as the primary focus of
  infection.
• Infrequently, usually in young adults, a viral
  pericarditis occurs as an apparent primary
  infection that may be accompanied by myocarditis
  (myopericarditis).
• Histologically, there is a mild inflammatory
  infiltrate in the epipericardial fat consisting
  predominantly of lymphocytes. Organization into
  fibrous adhesions rarely occurs.

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Acute pericarditis

• 2. Fibrinous and Serofibrinous Pericarditis
• Most frequent type of pericarditis
• Composed of serous fluid mixed with a fibrinous
  exudate
• Common causes include acute MI , the
  postinfarction (Dressler) syndrome (probably an
  autoimmune condition appearing several weeks
  after an MI), uremia, chest radiation, rheumatic
  fever, SLE, and trauma, or after routine cardiac
  surgery.
• The development of a loud pericardial friction
  rub is the most striking characteristic of
  fibrinous pericarditis
• Pain, systemic febrile reaction, and signs
  suggestive of cardiac failure may be present

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Acute pericarditis3. purulent / suppurative

• Caused by invasion of the pericardial space by
  microbes through
• (1) direct extension from neighboring
  infections, such as an empyema of the pleural
  cavity, lobar pneumonia, mediastinal infections,
  or extension of a ring abscess through the
  myocardium or aortic root
• (2) seeding from blood
• (3) lymphatic extension
• (4) direct introduction during cardiotomy
• Immunosuppression predisposes to infection by
  all of these pathways. The exudate ranges from a
  thin cloudy fluid to frank pus up to 400 to 500
  mL in volume. The serosal surfaces are reddened,
  granular, and coated with the exudate.

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Acute pericarditis- fibrinous and
fibrinopurulent

• Morphology Pericardial surface is dry, with a
  fine granular roughening. The inflammatory
  process induces the accumulation of larger
  amounts of yellow-brown turbid fluid which has
  leukocytes and red cells and often fibrin

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Acute pericarditispurulent / suppurative

• Microscopically there is an acute inflammatory
  reaction, which sometimes extends into
  surrounding structures to induce
  mediastinopericarditis
• Complete resolution is infrequent, and
  organization by scarring is the usual outcome-
  constrictive pericarditis
• Clinical findings in the active phase are
  essentially the same as those present in
  fibrinous pericarditis, but signs of systemic
  infection are usually marked for example,
  spiking temperatures, chills, and fever

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Acute pericarditis- 4. Hemorrhagic Pericarditis

• Exudate is composed of blood mixed with a
  fibrinous or suppurative effusion
• Most commonly caused by the spread of a
  malignant neoplasm to the pericardial space.
• Can also be found in bacterial infections,
  bleeding disorders, and in tuberculosis.
• Occasionally responsible for significant blood
  loss or even tamponade, requiring a "second-look"
  operation.
• Clinical significance is similar to that of
  fibrinous or suppurative pericarditis-
  constrictive pericarditis

48
Acute pericarditis-5. caseous pericarditis

• Tuberculous in origin, until proved otherwise
• Caseous (cheese like)
• Pericardial involvement occurs by direct spread
  from tuberculous foci within the tracheobronchial
  nodes

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Chronic or Healed Pericarditis

• In some cases organization produces plaquelike
  fibrous thickenings of the serosal membranes
  ("soldier's plaque") or thin, delicate adhesions
• Fibrosis in the form of delicate, stringy
  adhesions completely obliterates the pericardial
  sac- adhesive pericarditis, has no effect on
  cardiac function.
• Adhesive mediastinopericarditis may follow
  infectious pericarditis, previous cardiac
  surgery, or irradiation to the mediastinum.
• Pericardial sac is obliterated, and adherence of
  the external aspect of parietal layer to
  surrounding structures produces a great strain on
  cardiac function
• With each systolic contraction, the heart pulls
  not only against the parietal pericardium but
  also against the attached surrounding structures.
  
• Systolic retraction of the rib cage and
  diaphragm, pulsus paradoxus, and a variety of
  other characteristic clinical findings may be
  observed.
• Increased workload causes cardiac hypertrophy and
  dilation

50
Heart disease associated with rheumatologic
disorders

• Prevalence and importance of cardiovascular
  manifestations of rheumatologic diseases
  (including rheumatoid arthritis, SLE, systemic
  sclerosis, ankylosing spondylitis, and psoriatic
  arthritis) has increased as a result of the
  longer life expectancy of persons with these
  disorders and enhanced detection of milder cases
• Heart is involved in 20 to 40 of cases of
  severe prolonged rheumatoid arthritis- most
  common finding is a fibrinous pericarditis
• Granulomatous rheumatoid nodules may be seen

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Cardiac tumors
52
Tumors of the Heart

• Primary tumors of the heart are rare metastatic
  tumors to the heart occur in about 5 of persons
  dying of cancer
• The most common tumors are benign and
  collectively account for 80 to 90 of primary
  tumors of the heart

53
PRIMARY CARDIAC TUMORS-1. Myxoma

• Most common primary tumor of heart in adults
• Benign neoplasm often associated with clonal
  abnormalities of chromosomes 12 and 17
• About 90 are located in the atria (atrial
  myxomas), mostly in the region of fossa ovalis,
  with a left-to-right ratio of approximately 4
  1.

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1. myxoma

• Major clinical manifestations are due to valvular
  "ball-valve" obstruction, embolization, or a
  syndrome of constitutional symptoms, such as
  fever and malaise
• Diagnosis is by echocardiography
• Surgical removal is usually curative
• 10 individuals with myxoma have a familial
  syndrome (known as Carney complex) characterized
  by autosomal-dominant transmission, multiple
  cardiac and often extracardiac (e.g., skin)
  myxomas, pigmented skin lesions, and endocrine
  overactivity

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myxoma

Morphology. Usually single, rarely several .
Range in size from small (lt1 cm) to large (10
cm) sessile or pedunculated vary from globular
hard masses mottled with hemorrhage to soft,
translucent, papillary, or villous lesions having
a gelatinous appearance. The pedunculated
form is often sufficiently mobile to move into or
even through the AV valves during systole,
causing intermittent obstruction that may be
position-dependent. Sometimes mobile tumors exert
a "wrecking-ball" effect, causing damage to the
valve leaflets.
Left atrial myxoma. A, Large pedunculated lesion
arising from the region of the fossa ovalis and
extending into the mitral valve orifice B,
Microscopic appearance, with abundant amorphous
extracellular matrix in which there are scattered
collections of myxoma cells in various groupings,
including abnormal vessel-like formations (arrow)
56
2. lipoma

• Localized, well-circumscribed, benign tumors
  composed of mature fat cells that may occur in
  the subendocardium, subepicardium, or myocardium.
  
• May be asymptomatic, or produce ball-valve
  obstructions or arrhythmias.
• Most often located in the left ventricle, right
  atrium, or atrial septum
• In the atrial septum, non-neoplastic depositions
  of fat sometimes occur that are called
  "lipomatous hypertrophy."

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3. Papillary Fibroelastoma

• Usually incidental, sea-anemone-like lesions,
  most often identified at autopsy. They may
  embolize and thereby become clinically important
• They resemble the much smaller, usually trivial,
  Lambl excrescences that are frequently found on
  the aortic valves of older individuals.

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3. Papillary Fibroelastoma- morphology

• Papillary fibroelastomas are generally located on
  valves, particularly the ventricular surfaces of
  semilunar valves and the atrial surfaces of
  atrioventricular valves. They consist of a
  distinctive cluster of hairlike projections up to
  1 cm in length, and several centimeters in
  diameter.
• Histologically, the projections are composed of a
  core of myxoid connective tissue containing
  abundant mucopolysaccharide matrix and elastic
  fibers that is covered by a surface endothelium

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4. Rhabdomyoma

• Most frequent primary tumor of the heart in
  infants and children and are frequently
  discovered in the first years of life because of
  obstruction of a valvular orifice or cardiac
  chamber.
• Cardiac rhabdomyomas are often associated with
  tuberous sclerosis, which is caused by loss in
  the TSC1 or TSC2 tumor suppressor genes (TSC1 and
  TSC2 proteins work together in a complex that
  inhibits the activity of the mammalian target of
  rapamycin (mTOR), a kinase that stimulates cell
  growth and regulates cell size)
• Often regress spontaneously, rhabdomyomas are
  considered by some to be hamartomas rather than
  true neoplasms.

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4. Rhabdomyoma- morphology

• Generally small, gray-white myocardial masses
  several centimeters in diameter. They are usually
  multiple in number involve the ventricles
  preferentially, often protruding into the
  chambers
• Histologically they are composed of bizarre,
  markedly enlarged myocytes. Myocyte cytoplasm is
  often reduced to thin webs or strands that extend
  to cell membranes, an appearance referred to as
  spider cells

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Metastatic tumors

• Most frequent metastatic tumors involving the
  heart are carcinomas of the lung and breast,
  melanomas, leukemias, and lymphomas
• Metastases reach the heart and pericardium by
  retrograde lymphatic extension (most carcinomas),
  by hematogenous seeding (many tumors), by direct
  contiguous extension (primary carcinoma of the
  lung, breast, or esophagus), or by venous
  extension (tumors of the kidney or liver).
• Clinical symptoms associated with pericardial
  spread- symptomatic pericardial effusions or a
  mass-effect sufficient to restrict cardiac
  filling.
• Myocardial metastases usually clinically silent
  or have nonspecific features
• Bronchogenic carcinoma or malignant lymphoma
  infiltrate mediastinum causing encasement,
  compression, or invasion of the superior vena
  cava with obstruction to blood coming from the
  head and upper extremities (superior vena cava
  syndrome)
• Renal cell carcinoma can invades renal vein, and
  may grow as a frond of tissue up the inferior
  vena cava and into the right atrium, blocking
  venous return to the heart.

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CARDIAC EFFECTS OF NONCARDIAC NEOPLASMS

• Because of enhanced patient survival
  cardiovascular effects of noncardiac neoplasms
  and their therapy are now commonly encountered
• Direct consequences of tumor
• pericardial and myocardial metastaseslarge
  vessel obstructionpulmonary tumor emboli
• EFFECTS OF TUMOR THERAPY
• Complications of chemotherapy- Radiation used to
  treat breast, lung, or mediastinal neoplasms can
  cause pericarditis, pericardial effusion,
  myocardial fibrosis, and chronic pericardial
  disorders

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Cardiac Transplantation

• Transplantation of cardiac allografts is now
  frequently performed
• Most common causes are dilated cardiomyopathy and
  ischemic heart disease
• Three major factors have contributed to the
  improved outcome of cardiac transplantation (1)
  more effective immunosuppressive therapy (2)
  careful selection of candidates, and (3) early
  histopathologic diagnosis of acute allograft
  rejection by endomyocardial biopsy.
• Histology of rejection resembles myocarditis
• The major current limitation to the long-term
  success of cardiac transplantation is diffuse
  stenosing intimal proliferation of the coronary
  arteries, which may involve intramural vessels
  extensively (graft arteriopathy). Because the
  transplanted heart is often denervated, patients
  with this disorder may not experience ischemic
  chest pain, may lead to silent MI in severe
  graft arteriopathy, CHF or sudden death is the
  usual outcome
• Other postoperative problems include infection
  and malignancies, particularly Epstein-Barr
  virus-associated B cell lymphomas that arise in
  the setting of T-cell immunosuppression.