Depending on the pathogen and the host, viruses can potentially cause

F.06 Diseases of the Heart (Part 6) myocardial injury either as a direct cytopathic effect, or by eliciting
Dr. Domantay (Reporters) a destructive immune response. Inflammatory cytokines produced
in response to myocardial injury can also cause myocardial
dysfunction that is out of proportion to the degree of actual myocyte
Case 17 damage.
An 18-year old male complains of gradually progressing Direct cytopathic effect
shortness of breath and ankle swelling. His symptoms started following
an upper respiratory tract infection. He also complains of excessive
Myocardial injury
fatigue and frequent chest pain. He has no history of joint pain, skin Eliciting a destructive immune
rash, or involuntary movements, and is neither hypertensive nor response
diabetic.
PE – VS: tachycardia; hypotension; no fever. PE: elevated
JVP; pitting pedal edema; fine inspiratory rales at both lung bases; mild Inflammatory cytokines Myocardial dysfunction
tender hepatomegaly; splenomegaly; right sided S3; murmurs of mitral
regurgitation.
Labs – ASO titers not raised. CBC: lymphocytosis. Elevated 2. What structural changes are seen in the heart in this
ESR. ECG: first degree AV block with non-specific ST-T changes. patient’s disease?
Coxsackievirus isolated on pharyngeal washings; increased titers of
serum antibodies to coxsackievirus; elevated cardiac enzymes. Gross:
Imaging – CXR: cardiomegaly and pulmonary edema. Echo: • Flabby heart
suggestive of dilated cardiomyopathy with low ejection fraction • Softening and pallor of
ventricles
1. What heart disease does this patient most likely have? • Four chamber dilatation
MYOCARDITIS • Patchy hemorrhagic mottling
• Caused by infectious etiologies or primary autoimmune • Mural thrombi can form
dilated chambers
responses
• Clinical spectrum is BROAD, from entirely asymptomatic to • Endocardium and valves are
typically unaffected
abrupt onset of arrhythmia, CHF(Congestive Heart Failure) or
SCD(Sudden Cardiac Death) • Long term remodeling can lead
to dilation and hypertrophy
• Most patients recover quickly and without sequelae, although
DCM (Dilated Cardiomyopathy) can occur
2. What etiologies & mechanisms are involved in the patient’s disease? late stage: Fibrosis
Etiology
 Viral infections are the most common cause of myocarditis
o Most cases: Coxsackie viruses A & B and other
enteroviruses
o Cardiac involvement: occurs days to weeks after Myocarditis is
viral infection inflammation of the
o May be due to direct infection or secondary to myocardium associated
immunologic cross-reactivity (between with myocyte necrosis and
pathogen and myocardium) degeneration
 Less common etiologic agents
o Cytomegalovirus
o Influenza
Microscopically:
 Myocardial inflammatory infiltrate with associated myocyte
necrosis or degeneration
 Lesions are focal
o typically resolve over days to weeks variable interstitial
and replacement fibrosis

 A diffuse, mononuclear, predominantly lymphocytic

infiltrate is most common (Fig. 12-35A).
 Hypersensitivity myocarditis (Fig 12-35B) has interstitial
infiltrates, principally pervascular, composed of lymphocytes,
macrophages, and a high proportion of eosinophils.
 Giant-cell myocarditis (Fig. 12-35C) is characterized by a
widespread inflammatory cellular infiltrate containing multinucleate
giant cells intespered with lymphocytes, eosinophils, plasma cells,
and macrophages.
 Chagas disease (Fig 12-35D) is distinctive by virtue of the
parasitization of scattered myofibers by trypanosomes
accompanied by a mixed inflammatory infiltrate of neutrophils,
lymphocytes, macrophages, and occasional eosinophils.

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 • Compression of the thin walled atria and vena cava,
or the ventricles themselves
– Rapidly developing fluid collection: as little as 200-
300 ml (e.g. due to hemopericardium caused by
ruptured MI or aortic dissection)
– Cardiac filling is thereby restricted  potentially
fatal cardiac tamponade

Case 19
A 35-year old male complains of fever, nonproductive cough,
and chest pain. He states that the chest pain developed after he had a
severe cold for one week. He describes the pain as severe, crushing,
and constant over the anterior chest and adds that it worsens with
inspiration and is relieved by sitting up and bending forward.
PE – VS: low-grade fever; sinus tachycardia. PE: triphasic,
pericardial friction rub, elevated JVP; inappropriate increase in JVP with
inspiration; pulsus paradoxus seen
Labs – Moderately elevated transaminases and LDH: elevated
ESR; serum CK-MB normal. CBC: neutrophilic leukocytosis. ECG: diffuse
ST-segment elevation; PR-segment depression.
Echo: pericardial effusion. CXR: apparent cardiomegaly

1. What is the most likely diagnosis?

ACUTE PERICARDITIS
Case 18 • Pericardial inflammation
A 25-year old male who was stabbed in the chest during a
• Can occur secondary to a variety of causes
mugging is brought to the emergency room in a semi-conscious state,
• Acute primary pericarditis is chiefly viral in origin.
gasping for air. The knife penetrated the thoracic wall at the level of the
• Chronic pericarditis also occurs (e.g., with tuberculosis and
fourth intercostal space along the left sternal border.
fungal infections).
PE – VS: BP 90/40 that does not respond to rehydration;
inspiratory lowering of BP by > 10 mmHg. PE: increase in venous
pressure with inspiratory filling of neck veins during inspiration; during
drawing of venous blood, syringe filled spontaneously; apical impulse
diminished; heart muscle sounds seem distant; patient also cyanotic.
Labs – ECG: reduced voltage
Imaging – CXR: cardiomegaly, but with acute
hemopericardium. Echo: pericardial fluid; diastolic collapse of right
ventricle and atria

1. What is the most likely diagnosis (affecting the heart)?

CARDIAC TAMPONADE
Causes:
 Idiopathic
pericarditis
 Pericarditis 20 to
neoplastic disease
 Aortic dissection,
cardiac operation,
TRAUMA
 Bleeding
Beck’s Triad
 Hypotension 2. What are the different types of the acute and chronic forms of this
 Soft or absent heart patient’s disease? How do the types differ in terms of
sounds etiology and pathology?
 Jugular Venous a. ACUTE PERICARDITIS
distension 1. Serous Pericarditis
  Non-infectious inflammatory diseases
2. What types of fluid can accumulate in the pericardial sac? What are = Rheumatic fever (RF)
their respective etiologies? = Systemic Lupus Erythematosus (SLE)
The pericardial sac normally holds less than 50 mL of thin, clear, = Scleroderma
straw-colored fluid. = Tumors
• Serous fluid in pericardial effusion = Uremia
• Blood in hemopericardium  Contiguous infection (bacterial, viral)
• Pus in purulent pericarditis  Lymphatic invasion
3.What are the consequences of accumulation of fluid in the pericardial  Microscopically, there is scant pericardial acute and chronic
sac? inflammatory infiltration mostly lymphocytes
• Globular enlargement of the heart 2. Fibrinous and Serofibrinous Pericarditis
– Chronic effusions: less than 500mL  Most common form
 Serous fluid + fibrinous exudate

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  Clinical Findings: pain and fever, CHF, loud pericardial o Microscopic: acute inflammatory reaction  extends into
“friction rub” (most striking clinical finding) surrounding structures  mediastinopericarditis
 Causes:
= Acute MI
= Post-infarction (Dressler) Syndrome – an autoimmune
response appearing day-weeks after an MI) 4. Hemorrhagic Pericarditis
= Uremia  Blood + effusion (fibrinous or
= Chest radiation suppurative)
= RF, SLE, trauma  Most commonly caused by the
= Cardiac surgery spread of malignant neoplasm
 Associated Conditions:
= Bacterial infections
= Bleeding diathesis
= Tuberculosis
= Cardiac surgery (Tamponade)

5. Caseous Pericarditis
 Tuberculous in origin, unless
proven otherwise
 Infrequently caused by fungal
infections
 Mechanism: Direct spread from
Tuberculous foci (within
tracheobronchial nodes)
 “Common antecedent” of
disabling, fibrocalcific, chronic
Constrictive Pericarditis

b. CHRONIC/ HEALED PERICARDITIS

 Morphology:
i. Fibrinous pericarditis: dry surface with a fine granular
roughening
ii. Serofibrinous pericarditis: more intense inflammatory
process  larger amounts of yellow to brown turbid fluid,
containing leukocyts, erythrocytes, and fibrin
Fibrin may be lysed with resolution of the exudate, or can
become organized.

3. Purulent (Suppurative) 1. Adhesive mediastinopericarditis

Pericarditis Caused by:
 Reflects an active infection  Infectious pericarditis
caused by microbial invasion  Previous cardiac surgery
of the pericardial space via  Mediastinal irradiation
o Direct extension
(Empyema, Lobar
pneumonia, mediastinal
infections, or abscesses)
o Direct introduction
(Cardiotomy)
o Lymphatic extension
o Seeding from the blood
 Clinical Findings: marked;
spiking fevers and rigors
 Complication: Constrictive
PericarditiS
 Morphology:
o Gross: serosal srfaces are reddened, granular, and
coated with the exudate

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2. Constrictive pericarditis appearance)
 Caused by:  The pedunculated form is often sufficiently mobile to move
 Suppurative Pericarditis during systole into the atrioventricular valve opening ,
 Caseous Pericarditis causing intermittent obstruction that may be position-
 Hemorrhagic pericarditis dependent. Sometimes mobile tumors exert a “wrecking-
 Prior history may or may not be present ball” effect, causing damage to the valve leaflets.
 Heart is encased in a dense fibrous or fibrocalcific scar that
limits diastolic expansion and cardiac output, features that
mimic a restrictive cardiomyopathy
 Fibrous scar:
o Up to 1 cm thick
o Obliterates pericardial space
o Sometimes calcifying
o Plaster mold (concretio cordis)

MICROSCOPIC:
 Composed of stellate or globular myxoma cells
o Clusters or Singly
o Irregular cytoplasm and dark nuclei
CASE 20  Abundant acid mucopolysaccharide ground substance
A 50-year old woman complains of recurrent, transient loss of  Peculiar vessel-like or gland-like structures are characteristic
consciousness and dizziness. For the past few months, she has had  Hemorrhage and mononuclear inflammation are usually
continuous mild to moderate fever, fatigue, swelling, and joint pains and present
has experienced unexplainable breathlessness at rest that is relieved in
a supine position and exacerbated by standing. She also complains of 3. What other masses can arise in the heart? How do they differ in
significant weight loss over the past year. their gross and microscopic features?
PE – VS: mild fever. PE: pallor and clubbing; on auscultation,
S1 delayed and decreased in intensity and characteristic low-pitched Cardiac Lipoma
sound during diastole, followed by a rumble; auscultatory findings vary Lipomas are localized, well-circumscribed, benign tumors composed
with position. of mature fat cells that can occur in the subendocardium,
Labs – CBC: normochromic, normocytic anemia. Elevated subepicardium, or myocardium. They may be asymptomatic, or
ESR; increased IgG; blood cultures sterile. ECG: sinus rhythm produce ball-valve obstructions or arrhythmias. Lipomas are most often
Imaging – Echo (2D): characteristic echo-producing mass in located in the left ventricle, right atrium, or atrial septum. In the atrial
left atrium. MR, cardiac: globular mass in the left atrium septum, nonneoplastic depositions of fat sometimes occur that are
called “lipomatous hypertrophy.” These lesions include white and
1. What is the most likely diagnosis? brown adipose tissue, as well as small-interspersed areas of
myocardium.
LEFT ATRIAL MYXOMA GROSS
Myxomas are the most common primary tumor of the adult • Spherical/ elliptical mass of
heart are benign neoplasms thought to arise from primitive multipotent homogenous yellow fat
mesenchymal cells. Although sporadic myxomas do not show consistent • Large (15cm), infiltrates
genetic alterations, familial syndromes associated with myxomas have myocardium, extend to RA and
activating mutations in the GNAS1 gene, encoding a subunit of G ventricle
• Pericardium: thickened, white-
protein (Gsα) (in association with McCune-Albright syndrome) or null
greyish
mutations in PRKAR1A, encoding a regulatory subunit of a cyclic-AMP- • Poorly encapsulated
dependent protein kinase (Carney complex). About 90% of myxomas • Circumscribed
arise in the atria, with a left-to-right ratio of approximately 4: 1.

2. What are the gross and microscopic features of this patient’s

lesion? MICROSCOPIC
GROSS: • With mature adipocytes
 Tumors are usually single, but can rarely be multiple. • Myocytes at the periphery
 Favors the region of the fossa ovalis in the atrial septum
 Small (1cm) to large (>10cm)
 Sessile or Pedunculated
 Globular hard masses mottled with hemorrhage to soft,
translucent, papillary or villous lesions (gelatinous

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Papillary Fibroelastoma Angiosarcoma
Papillary fibroelastomasare curious, usually  GROSS
incidental, sea-anemone-like lesions, most often identified at • Lobulated,
autopsy. They may embolize and thereby become clinically important. variegated,
Clonal cytogenetic abnormalities have been reported, suggesting that hemorrhagic mass
fibroelastomas are unusual benign neoplasms. They resemble the much • Atleast 2cm
smaller, usually trivial, Lambl excrescences that may represent • Dark, grey-brown to
remotely organized thrombus on the aortic valves of older individuals. black, some yellow-
white
GROSS • Variegated- diff
 usually (>80%) located on colors, irregular
valves, particularly the patches or sretch
ventricular surfaces of Angiosarcomas usually form lobulated variegated masses in the
semilunar valves and the right atrial wall, protruding into the chamber. They range from 2.0 cm
atrial surfaces of to several centimeters. The masses are classically dark, grey-brown to
atrioventricular valves black in colour and may resemble a melanoma, but tumours with less
 Each lesion, typically 1 to 2 cm in well-developed vascular spaces may appear firm, yellow-white in colour,
diameter, consists of a distinctive lacking the classic hemorrhagic appearance. The pericardium is
cluster of hairlike projections frequently involved and hence a hemorrhagic pericardial effusion is a
up to 1 cm in length. frequent accompaniment. While involvement of the tricuspid valve and
MICROSCOPIC extension or invasion of the vena cavae is reported, involvement of the
 the projections are covered by a pulmonary artery and interatrial septum are unusual. In rare instances,
surface endothelium the pericardium is the sole site of involvement.
surrounding a core of myxoid
connective tissue with  MICROSCOPIC
abundant • Pleomorphic and atypical
mucopolysaccharide matrix lining cells
and elastic fibers. • Cord-like structures
• Eosinophilic cytoplasm
• Occasional cytoplasmic
vacuoles
Rhabdomyoma
Over two-thirds of cardiac
Rhabdomyomas are the most frequent primary tumor of the angiosarcomas are well to
pediatric heart, and are commonly discovered in the first years of life moderately differentiated
because of obstruction of a valvular orifice or cardiac chamber. showing well-formed vascular
Approximately half of cardiac rhabdomyomas are due to sporadic muta- channels and papillary
tions; the other 50% of cases are associated with tuberous sclerosis, structures. The vascular
with mutations in the TSC1 or TSC2 tumor suppressor gene. The channels are irregular,
TSC1 and TSC2 proteins (hamartin and tuberin, respectively) function anastomosing, and sinusoidal.
in a complex that inhibits the activity of the mammalian target of The lining cells are usually
rapa- mycin (mTOR), a kinase that stimulates cell growth and pleomorphic and atypical. They
regulates cell size. TSC1 or TSC2 expression is often absent in tuberous may form cord-like structures
sclerosis-associated rhabdomyomas, providing a mechanism for in which lumina are difficult to
myocyte overgrowth. Because rhabdomyomas often regress demonstrate. Mitoses are
spontaneously, they may be considered as hamartomas rather than usually present. The remaining third are poorly differentiated and
true neoplasms. composed predominantly of anaplastic spindle cells. In angiosarcoma
with a focal or dominant spindle cell pattern, poorly formed vascular
 GROSS channels and extravascular red blood cells can usually be identified
• Gray-white myocardial masses focally.
• Small up to several centimeters
in diameter
• Usually multiple and involve the
ventricles preferentially,
protruding into the lumen

 MICROSCOPIC
• composed of bizarre,
markedly enlarged myocytes
• Routine histologic processing
often artifactually reduces
the abundant cytoplasm to
thin strands that stretch
from the nucleus to the
surface membrane, an
appearance referred to as
“spider” cells.

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