Cardiac Pathology

1
Cardiac Pathology
2
(No Transcript)
3
Topics covered

• Transplant pathology
• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• tumors
• Valvular heart disease
• Vasculitis

4
Topics not covered

• Plaque morphology classification
• Nonatheromatous CAD
• Pericardial diseases
• Congenital heart disease

5
Transplantation

• A couple of questions can show up on boards.
• 1. grading system for heart transplant
• 2. Quilty lesion

6
Transplant

• Hyperacute rejection
• -is rare but develops immediately or hours
  after transplantation and results in graft
  failure.
• -Histologically hemorrhage and edema and
  platelet aggregates in blood vessels are seen.
  With time polys are seen.
• Acute rejection
• -Lymphocytes, macrophages and eos.
• -No neutrophils
• (polys indicate ischemia, antibody mediated
  rejection or infection.)
• -No plasma cells (they indicate a Quilty
  lesion or PTLD)

7
Transplant

• Eos
• can indicate toxoplasmosis, CMV or drug
  reaction
• Acute antibody mediated rejection
• -the controversy
• -capillary injury, endothelial swelling and
  intravascular macrophages
• - edema, hemorrhage, neutrophils near
  capillaries, thrombi and myocyte necrosis.
• -IgG, IgM, IgA, C3d, C4d, C1q,

8
ISHLT CARDIAC GRADING
9
Transplant

• In the old classification, it was not easy to
  separate grade 2 rejection from grade 1B, grade 3
  or Quilty effect.
• In the new classification, it is now known that
  one focus of myocyte damage (Grade 1R) has a low
  probability of progression and probably does not
  need treatment.

10
Question 23
11
Question 23

• This lesion is most likely o be seen in an
  endomyocardial biopsy from a patient with
• SLE
• AIDS
• A transplanted heart
• Chagas disease
• MacCallums plague

12
Answer C, Quilty effect

• Quilty effect Dense lymphocytes within the
  endocardium
• Quilty B lesions are similar, but they extend
  into the underlying subendocardium
• Sparse endocardial infiltrates can be in
  rejection
• T cells, B cells, plasma cells, macs, thin walled
  blood vessels
• Quilty is B T cells, rejection is usually T
  cells
• Often in patients on cyclosporine,
• Usually do not persist, but recurrences can
  happen.
• Usually in only one piece of tissue

13
Topics covered

• Ischemic heart disease

14
(No Transcript)
15
Types of atherosclerotic plaque

• (adaptive intimal thickening)
• Fatty streak
• Pathologic intimal thickening
• Fibroatheroma
• Complicated fibroatheromas
• Hemorrhage and thrombosis

16
Sites

• Aorta, especially abdominal and infrarenal
• Coronary arteries
• Arteries in lower extremitiesiliac
• Cerebral arteries, carotid, circle of Willis
• Often at bifurcations of arteries
• Spares, upper extremities, aortic arch,
  mesenteric

17
Atherosclerosis

• A disease affecting arteries in which patchy
  intimal athickening and secondary medial
  degeneration lead to weakening of the vessel wall
  and narrowing of the lumen

18
Blood vessel anatomy
Adventitia Media Intima
Inside Blood vessel
Outside Blood vessel
19
Microscopic plaque
Lipid core (Macrophages, cholesterol)
Fibrous cap
20
The primary lesion is in the intima Lipid
core fibrous cap
21
Medial changes are secondary Loss of elastic
fibers Thin fibrosis
The primary lesion is in the intima Lipid
core fibrous cap
22
(No Transcript)
23
(No Transcript)
24
Fate of coronary thrombi Healed plaque rupture
25
EBCT
26
Major risk factors for coronary atherosclerosis

• Modifiable
• Dyslipidemia
• Hypertension
• Diabetes
• Central obesity/insulin resistance/metabolic
  syndrome
• Cigarette smoking
• Fixed Age, gender (MgtF), family history

27
Newer risk factors

• Inflammatory
• CRP, ferritin, leukocyte count
• Thrombotic
• ?Fibrinogen, ?FVII,
• Lipids-Lp(a), ApoE
• Homocysteine

28
Cellular components of atherosclerosis
Lymphocyte
Platelet
Endothelial cell
Smooth muscle cell
Macrophage
29
Synopsis

• Atherosclerosis is a unique form of wound healing
  triggered by intra-arterial accumulation of lipid
  and dying smooth muscle cells
• Macrophages are unable to clear the lesion due to
  intimal location
• Ongoing thrombosis is probably critical in plaque
  enlargement and continuing recruitment of
  activated inflammatory cells as well as sudden
  occlusion

30
Ischemic Heart (Coronary) Disease

• Closely related syndromes caused by an imbalance
  between myocardial O2 demand and blood supply.
  The most common cause is atherosclerosis of the
  coronary arteries.

31
IHD - Pathogenesis
Critical stenosis occurs when 75 of the lumen of
one or more coronary artery is obstructed by
atherosclerotic plaque. With this fixed level of
obstruction, compensatory coronary vasodilation
is insufficient to meet moderate increases in
myocardial O2 demand leading to ischemia.
32
Ischemic Heart Disease (IHD)

• 1. Fixed obstruction - 75 of lumen
• 2. Superimposed plaque lesions
• -Acute changes in plaque morphology
• -thrombosis
• -vasospasm
• -vasodilation

33
(No Transcript)
34
Compensatory remodeling

• The coronary arteries get bigger as disease
  progresses, so the lumins stay the same size.
• Does luminal thrombosis matter?

35
Atherosclerosiscomplications

• Occlusion - ischemia
• Tortuosity / aneurysms
• Rupture
• Thromboembolism

36
(No Transcript)
37
(No Transcript)
38
Myocardial Infarction (MI)

• MI is the development of a defined area of
  myocardial necrosis gt 1 cm in size caused by
  local ischemia. The most common cause is
  coronary thrombosis due to atherosclerotic plaque.

39
Gross evolution of myocardial infarct

• lt 2 days Hard to see pallor
• Tetrazolium salts lack of staining
• 2-4 days Yellow necrotic zone surrounded by
  hyperemic zone
• Later infarcts Gelatinous granulation tissue
  progressing to scar

40
Dog heart acute infarct
1-2 day infarct
3 day infarct with rupture
Healed infarct
41
Sequence of Changes in MI
42
(No Transcript)
43
Sequence of Changes in MI
44
(No Transcript)
45
AMI - Microscopic Morphology
Coagulation Necrosis Inflammation
? Granulation Tissue ? Resorption of Necrotic
Debris ? Organization Scar
46
What about this case?

• A 49 year old woman had crushing substernal pain
  for 3 hrs followed by IV streptokinase
• EKG showed ST elevations c/w MI

47
(No Transcript)
48
Reperfusionheart muscle that is reperfused

• May result from balloon angioplasty, and
  thrombolysis therapy
• Acceleration in the aging of the infarct
• More hemorrhage within infarct
• More contraction band necrosis

49
Nonatherosclerotic Causes of IHD

• Congenital anomalies
• Anomalous origin of LAD
• Kawasaki disease
• Fever, conjunctival congestion, oral erythema,
  rash and lymphadenopathy
• Coronary arteries with necrotizing inflammation
  and aneurysms
• TTP/HUS/DIC

50
AMI - Complications

• Papillary muscle dysfunction/rupture
• External rupture of the infarct
• IV septal rupture
• Mural thrombosis
• Ventricular aneurysm

51
Question 24
52
Question 24

• The lesion indicated by the arrow followed the
  acute onset of severe chest pain in a 56-year-old
  man. The interval between the onset of chest
  pain and death was probably.
• A. 6 minutes
• B. 6 hours
• C. 6 days
• D. 6 weeks
• E. 6 months

53
Answer C

• This looks like rupture of the free wall of the
  ventricle. This is most frequent 3 to 7 days
  after onset of a myocardial infarction.

54
Complication of acute infarct rupture

• Associations Hypertension, first infarct,
  female sex
• Peak occurrence 3 days, may occur at any time

55
(No Transcript)
56
(No Transcript)
57
More complications

• Aneurysmcan lead to embolism or stroke
• Scarring of papillary muscle
• Arrythmiasee nothing grossly

58
(No Transcript)
59
Topics covered

• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• Primary myocardial diseases (tumors)
• Valvular heart disease
• Congenital heart disease
• Vasculitis

60
Myocarditis

• Inflammation
• Resulting in injury to cardiac myocytes
  (necrosis and/or degeneration) not typical of IHD
• Infections
• Cardiac allograft rejection
• Collagen vascular diseases
• Drug hypersensitivity
• Sarcoidosis

61
Myocarditis

• Infectious Agents
• Viruses (most common cause in USA)
• Coxsackieviruses A B and other enteroviruses
  (most common agents)
• Cytomegalovirus
• HIV

62
Myocarditis

• Parasites
• Chagas disease (Trypanosoma cruzi)
• Toxoplasmosis
• Trichinosis

63
Myocarditis

• Bacteria
• Lyme disease
• Diphtheria (injury from toxins of Corynebacterium
  diphtheriae)

64
Myocarditis

• Clinical Features
• Asymptomatic
• Congestive failure
• Arrhythmias
• Usually self-limited
• Morphology (Gross)
• Cardiac dilation
• Myocardium flabby, pale, with focal hemorrhages

65
(No Transcript)
66
Myocarditis

• Morphology
• Acute viral
• 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

67
(No Transcript)
68
(No Transcript)
69
(No Transcript)
70
Giant cell myocarditis

• Fiedlers myocarditis
• Rapidly progressing disease of young adults
• MN giant cells, lymphocytes, eos, necrosis
• Differential sarcoid, hypersensitivity
• Aggressive clinical course indication for
  transplant

71
(No Transcript)
72
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)

73
(No Transcript)
74
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

75
(No Transcript)
76
Rheumatic carditis

• Uncommon cause of myocarditis
• Aschoff nodule
• Anitschkow cell (histiocytes)
• Aschoff cells (MN giant cells)
• Collagenolysis
• Pancarditis

77
(No Transcript)
78
(No Transcript)
79
Topics covered

• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• Primary myocardial diseases (tumors)
• Valvular heart disease
• Congenital heart disease
• Vasculitis

80
Cardiomyopathies

• Definition Heart muscle disorder of unknown
  etiology, although we do sometimes know the cause
• Diagnosis of exclusion
• 3 types
• Dilated (congestive) (90)
• Hypertrophic (lt 10)
• Restrictive (lt 2)

81
Dilated Cardiomyopathy

• Description
• Progressive cardiac hypertrophy, dilation, and
  systolic dysfunction (pump failure)
• Causes
• Postviral myocarditis (late stage)
• Postpartum
• Alcohol toxicity
• Familial
• Drug (Adriamycin)
• Idiopathic

82
Dilated Cardiomyopathy

• Gross
• Heart enlarged and flabby
• Weight may exceed 900 grams
• Dilation of all four chambers
• ventricles gt atria

83
(No Transcript)
84
Dilated CardiomyopathyMicroscopic

• Nonspecific
• Myocyte hypertrophy
• Interstitial fibrosis
• Wavy fiber change or myofiber loss
• Scanty mononuclear inflammatory infiltrate

85
(No Transcript)
86
Arrhythmogenic RV Dysplasia

• Uncommon, familial form that affects young adults
  causing sudden death
• RV is markedly thinned replaced by fat

87
(No Transcript)
88
Hypertrophic Cardiomyopathy

• Defect in ß myosin heavy chain on chromosome 14
  (50)
• Sudden death with excersize
• thick septum (90),
• thick mitral valve, large left atrium and small
  left ventricular cavity.
• Microscopic myofiber disarray

89
Asymetric hypertrophy
90
(No Transcript)
91
Restrictive Cardiomyopathy

• Primary decrease in ventricular
• compliance, resulting in impaired
• cardiac output.

92
Restrictive Cardiomyopathy

• Causes
• Endomyocardial fibrosis
• Common cause worldwide
• 10 of cases of childhood heart disease in
  tropical regions
• Infiltrative heart disease (amyloid, HH)
• Idiopathic

93
Restrictive Cardiomyopathy

• Gross
• Varies depending on cause
• Atrial dilation (bilateral)
• Endocardium thickened and opaque
• Valvular thickening
• Mural thrombi may be present
• Microscopic
• Dense endocardial fibrosis, extending into
  subendocardial myocardium

94
Idiopathic restrictive cardiomyopathy Biatrial
dilatation, grossly normal ventricles
95
(No Transcript)
96
Cardiac amyloid

• Three main types
• AL (light chains, plasma cell neoplasm)
• 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

97
(No Transcript)
98
Hemochromatosis

• Iron not normally found in heart
• C282Y or H63D mutation
• HLA-associated TfR gene
• Dilated or restrictive cardiomyopathy

99
(No Transcript)
100
Fabrys Disease

• X-linked recessive form of sphingolipidosis due
  to deficiency of alpha-galactosidase A
• angiokeratomas, renal insufficiency cardiac
  failure
• Histology vacuolated myocytes
• EM shows intralysosomal dense lamallae with
  concentric or packed arrangment (Zebra bodies)

101
Drug-induced cardiomyopathy

• Adriamycin
• 1.7 incidence of toxicity
• Grading scheme based on sarcotubular dilatation
  (vacuolization) and myofibrillar loss
• process all for EM

102
Topics covered

• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• Primary myocardial diseases (tumors)
• Valvular heart disease
• Congenital heart disease
• Vasculitis

103
(No Transcript)
104
Myxomas

• Most common unknown histogenesis
• Majority in left atrium (75)
• Mostly sporadic some associated with Carneys
  complex/triad, familial myxomatous syndrome or TS
  complex

105
Which is Which?

• Carneys Syndrome
• Cutaneous cardiac myxomas (myxoid FAs)
• Spotty skin pigmentation (lentigines blue nevi)
• Endocrine overactivity
• Adrenal, testicular, thyroid pituitary

• Carneys Triad
• Multiple pulmonary chondromas
• GISTs of the stomach
• Extra-adrenal paragangliomas
• Autosomal dominant
• 2p16

106
(No Transcript)
107
Rhabdomyomas

• Most common primary cardiac tumor of infancy and
  childhood
• May be isolated but gt50 associated with TS
• Eosinophilic, polygonal cells with large
  glycogen-rich cytoplasmic vacuoles with stranding
  spider cells

108
Cardiac Tumors

• Primary tumors are rare (most are benign)
• Metastases far more common (20-40X)

109
Metastatic Neoplasms

• Most common cardiac neoplasms
• Lung
• Breast
• Melanomas
• Lymphomas
• Leukemias

110
(No Transcript)
111
Topics covered

• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• Primary myocardial diseases (tumors)
• Valvular heart disease
• Congenital heart disease
• Vasculitis

112
Biscuspid Aortic Valve

• Second most common valve defect after MVP
• Most common cause of isolated AS in adults
• Etiology and Demographics
• Congenital, 1 of population
• 5th to 7th decades
• The two leaflets are usually of unequal size

113
Complications

• Infectious endocarditis (10-40)
• Aortic dissection (1-2)

114
(No Transcript)
115
Rheumatic Valve Disease

• Definition Acute, immunologically mediated,
  multisystem inflammatory disease following group
  A streptococcal pharyngitis.
• 3 of patients with group A streptococcal
  pharyngitis
• All 4 valves (MV gt AV gt TV gt PV)
• Febrile illness with rash, transitory arthritis,
  pancarditis and/or chorea 2-4 wks after GAS
  pharyngitis

116
Acute Rheumatic Heart Disease

• Endocarditis
• small excrescences along line of valve closure
• Myocardium
• Aschoff nodules
• Pericarium
• Fibrinous pericarditis

117
(No Transcript)
118
(No Transcript)
119
(No Transcript)
120
(No Transcript)
121
Chronic Rheumatic Heart Disease

• Latent period (20-30 years) before symptoms
  appear
• commissural fusion, cusp fibrosis, retraction,
  calcification
• Shortening and thickening of chordae

122
(No Transcript)
123
(No Transcript)
124
Mitral Valve Prolapse

• General Information
• Most common cause of isolated mitral
  regurgitation
• 5 of adult population
• Ages 20 to 40
• women gt men
• Mitral valve floppy or incompetent
• May occur with Marfans syndrome

125
Mitral Valve Prolapse

• Morphology
• Mitral valve cusps (posterior cusp) soft,
  enlarged, and ballooned into left atrium during
  systole
• Loose, edematous, basophilic (acid
  mucopolysaccharide) ground substance
• Complications include endocarditis, chordal
  rupture, arrythmia, annular calcification or
  sudden death

126
(No Transcript)
127
(No Transcript)
128
(No Transcript)
129
(No Transcript)
130
Dilated left atrium
MAC
Marantic endocarditis
131
Infective Endocarditis

• Infection of the cardiac valves or mural surface
  of the endocardium, with formation of adherent
  mass of thrombotic debris and organisms, termed a
  vegetation.
• Any microorganism but most cases are bacterial
• Underlying valve abnormality ? risk of infective
  endocarditis.

132
Infective Endocarditis

• New onset murmur bacteremia /- embolic lesions
• AV MV most common TV in IVDA
• Complications include septic emboli, abscesses,
  pyogenic myocarditis, incompetent valves, death

133
Associations

• S. aureus IVDA
• S. epidermidis prosthetic valves
• S. viridans Sub acute
• Enterococci normal/damaged valves
• S. bovis colon CA
• Pneumococcus alcoholics
• G negative IVDA, DM, immunocompromised
• Fungal IVDA, immunocompromised

134
(No Transcript)
135
Culture negative endocarditis

• 5-10 of cases
• Prior treatment
• Fastidious organisms
• HACEK, mycobacteria
• Intracellular organisms
• Rickettsia, Q-fever, Whipples

136
Nonbacterial Thrombotic Endocarditis (Marantic)

• Deposition of fibrin platelets on leaflets of
  cardiac valves.
• Lesions do not contain microorganisms
• Valves usually previously normal
• Assoc with malignancies cachexia
  (hypercoagulable states)
• AV MV

137
Nonbacterial Thrombotic Endocarditis (Marantic)

• Gross
• Small nodules on lines of closure

• Microscopic
• Fibrin platelets
• Free of inflammation

138
(No Transcript)
139
(No Transcript)
140
Lupus erythematosus

• Libman-Sacks lesions
• Flat lesions covering both sides of valve
  surfaces
• Usually ventricular and extend to papillary
  muscles
• Fibrinoid necrosis inflammation

141
(No Transcript)
142
Topics covered

• Ischemic heart disease
• Myocarditis
• Cardiomyopathies
• Primary myocardial diseases (tumors)
• Valvular heart disease
• Diseased of the aorta and vasculitis

143
Question 25
144
Question 25

• This lesion of the aorta is associated with each
  of the following EXCEPT
• A specific form of cancer
• B An inherited disorder of metabolism
• C Pregnancy
• D Systemic hypertension
• E Middle age (40-60 years)

145
Answer A.

• Aortic dissection is associated with hypertension
  in middle aged patients and rarely with
  pregnancy. There is no direct association with
  cancer.

146
Read my notes on dissecting aortic aneurysms
147
(No Transcript)
148
Luetic aortitis
149
Vasculitis

• Large vessels
• -- Giant cell
• -- Takayasu
• Medium vessels
• -- PAN
• Small vessels
• -- HSP
• --sle
• -- cryoglobulinemia
• -- Good pasture
• --Wegeners
• --Churg Strauss
• --microscopic polyangiits

150
Vasculitis

• Large vessels
• -- Giant cell
• -- Takayasu
• Medium vessels
• -- PAN
• Small vessels
• -- HSP
• -- sle
• -- cryoglobulinemia
• -- Good pasture
• -- Wegeners
• -- Churg Strauss
• -- microscopic polyangiitis

unknown
Immune complex direct antibody
ANCA
151
Takayasus disease

• Pulseless disease in young Asian females
• Stenoses with skip lesions in
• Medial destruction, fibrointimal proliferation
  thrombus formation

152
(No Transcript)
153
Diseases of the Aorta

• Giant cell aortitis/arteritis
• Fragmented elastic fibers
• Giant cell response
• Giant cells not required for temporal arteritis
• Only destruction of internal elastica with
  inflammation
• Temporal arteritis in elderly
• False negatives due to focal distribution and
• Rx before biopsy (3-5 cm)
• Polymyalgia rheumatica (muscle pain)

154
Giant cell aortitis
155
Temporal arteritis
156
ANCA (antineutrophil cytoplasmic autoantibodies)

• Indirect immunofluorescence currently ELISA
  available
• cANCA cytoplasmic staining,
• alternative leukocyte protease (3)
• pANCA perinuclear staining
• alternative myeloperoxidase

157
pANCA
cANCA
158
Wegeners granulomatosis

• Triad upper respiratory tract, lung, kidneys
• Necrosis, vasculitis and granulomas
• cANCA () in gt 90 of cases

159
(No Transcript)
160
ANCA
Not all patients with Wegeners have C-ANCA and
patients with Wegeners can have a P-ANCA
161