AFECŢIUNILE INIMII

Heart pathology.

ЗАБОЛЕВАНИЯ СЕРДЦА
 Heart pathology.

I. Microspecimens:
№ 181. Coronary artery thrombosis in atherosclerosis. (H-E stain).
Indications:
1. Stenosing atherosclerotic plaque in the artery wall.
2. Recent red thrombus on the atherosclerotic plaque surface.
3. The adjacent heart muscle.
Cross section through the subepicardial coronary artery with the underlying myocardium. With the naked eye it can
be seen that the lumen of the artery is blocked with thrombotic masses, in the wall an atherosclerotic plaque is
observed, which stenoses the lumen. At lower resolution, can be observed that the thrombus is predominantly
composed of fibrin and hemolyzed erythrocytes, it adheres intimately to the fibrous capsule of the atherosclerotic
plaque, in the thickness of which the weaker eosinophilic colored necrotic center / nucleus is revealed, surrounded by
an inflammatory cell infiltrate. In the myocardium protein dystrophy of cardiomyocytes, hemodynamic disorders in
the microcirculatory system.
Coronary artery thrombosis is the most common cause of myocardial infarction and occurs in the vast majority of
cases due to stenotic atherosclerosis of the coronary arteries. Thrombus usually develops on so-called "unstable" or
"vulnerable" atheromas, in which the fibrous capsule is thin, fine, necrotic center rich in lipids, with active
inflammation, the plaques being susceptible to erosion, ulceration, rupture, intramural hemorrhage.

№ 65. Acute myocardial infarction. (H-E stain).

Indications:
1. Infarct area (karyolysis).
2. Adjacent myocardium.

In the myocardium there are areas of necrosis with cardiomyocyte caryolysis, sarcoplasmic eosinophilia, some cells
in disintegration (plasmo-cytorexis), at the periphery of necrotic foci hemorrhages, leukocyte infiltration, in adjacent
areas cardiomyocytes with stromal edema, 2 neighboring cells were detected - one necrotic, anucleated and another
with a persistent nucleus.
 2
1

№ 181. Coronary artery thrombosis in atherosclerosis. (H-E stain).

 1

№ 65. Acute myocardial infarction. (H-E stain).

№ 65a. Myocardial infarction in stage of organization. (H-E stain).
Indications:
1. Infarct area.
2. Leukocyte infiltration at the periphery of the infarct area.
3. Granulation tissue around the area of necrosis.
4. Adjacent myocardium.
In the myocardium necrotic foci are detected with cardiomyocyte caryolysis, some cells with signs of
plasma cytorexis, in some places form homogeneous, structured eosinophilic foci (necrotic detritus),
leukocyte infiltration and hemorrhages are observed; these areas are surrounded by granular tissue rich in
capillaries and cellular elements; in the adjacent heart muscle protein dystrophy of cardiomyocytes, stromal
edema.

In the temporal evolution of myocardial infarction, the stage of necrosis and the stage of organization are
distinguished. The stage of necrosis is manifested microscopically by cardiomyocyte caryolysis, their
fragmentation, leukocyte infiltration, which reaches a maximum 48-72 hours after the onset of infarction,
hyperemia of the vessels, hemorrhagic foci. Macroscopically, the area has an irregular shape, white-yellow
color in the center and red edema on the periphery - white, ischemic infarction with hemorrhagic edema.
Very rarely, in 1-2%, myocardial infarction can be hemorrhagic. The organization of the infarction shows the
process of substituting the necrotic focus with granulation tissue. On the 4th day after onset, macrophages
begin to appear in the area of ​necrosis, which performs the resorption of necrotic masses and gradually
replaces the necrosis with granulation tissue, which penetrates from adjacent areas of the heart muscle.
Subsequently, the granulation tissue matures, collagenizes and transforms into mature, dense scar
fibroconjunctival tissue. The healing process of myocardial infarction with the development of post-infarction
macrofocal cardiosclerosis lasts on average 6-7 weeks, depending on the size of the infarction and the
general condition of the body. Complications of acute myocardial infarction: a) cardiogenic shock, b) acute
heart failure, c) pulmonary oedema, d) arrhythmias (ventricular fibrillation, asystole and a.), E) rupture of
the ventricular wall with pericardial tamponade, f) fibrinous pericarditis, g) intracardiac wall thrombosis
and thromboembolism and others.
 4

№ 65a. Myocardial infarction in stage of organization. (H-E stain).

№ 59. Rheumatic granulomatous endo-myocarditis. (H-E stain).
Indications:
1. Aschoff rheumatic granulomas in the parietal endocardium.
2. Fibrinous necrosis in the center of the granuloma.
3. Macrophages at the periphery of the granuloma.
4. Adjacent myocardium.

There are 2 series of microspecimens:

I - cross section through the left auricle of the heart; at the lower resolution, in the parietal endocardium,
which covers the auricle’s wall, small focal agglomerations of polymorphic cellular elements are detected -
Ashoff rheumatoid granulomas, at the large objective it is seen that they are composed of lymphocytes,
macrophages and fibroblasts, in the center of some granulomas necrosis with eosinophilic colored tissue
debris (fibrinoid necrosis);
II – cut section of the ventricular wall with the parietal endocardium, rheumatic granulomas are observed in
the endocardium and in the subendocardial myocardium, especially perivascular.

Aschoff's granuloma is pathognomonic for rheumatism. It is found in all layers of the heart (in rheumatic
pancarditis) and in other organs and tissues. There are 3 stages in the evolution of granuloma: 1) early or
degenerative, 2) intermediate or proliferative (florid) and 3) late or healing (involutive). In the first stage
dystrophic changes and fibrinoid necrosis of connective tissue predominate, in the second stage - cell
proliferation with the accumulation of lymphocytes, macrophages, plasma cells and Anitschkow cells, which
are arranged in the palisade around fibrinoid masses, in the third stage - processes fibrosis and sclerosis.
Anitschkow cells or cardiac histiocytes are macrophages with an elongated, wavy, caterpillar-shaped nucleus
(cartilage cells), some of which become polynuclear, with 1-4 nuclei, which are called Ashoff cells and are
considered characteristic of rheumatic carditis. The evolution of the granuloma until scarring lasts on
average 3-4 months, on the place of the granuloma a fibroconjunctive scar is formed, located predominantly
perivascular.
 2

№ 59. Rheumatic granulomatous endo-myocarditis. (H-E stain).

II. Macrospecimens:

№ 24. Heart rupture (left ventricle) in acute myocardial infarction.

In the lower third of anterior wall of the left ventricle, a fissure with a length of 1.5-2 cm is observed, on
the section it is seen that the fissure comprises the entire thickness of the ventricular wall, the edges are
infiltrated with blood.

Rupture of the heart is the cause of death in 10% of the total number of patients who die from myocardial
infarction. There is external and internal rupture. The rupture occurs in cases of macrofocal, transmural
infarction, affecting at least 20% of the heart muscle, usually in the first days after the onset of the infarction
(days 1-4), when the process of myomalacia develops - autolysis of the necrosis area under the influence of
proteolytic enzymes of neutrophil leukocytes. The rupture occurs more frequently at the border between the
area of necrosis and the persistent myocardium. The rupture in the center of the infarct area is observed more
frequently in the second week, during the organization of the infarction. Most external ruptures of the heart
occur in the left ventricle, anterior and lateral walls. Develops, hemopericardium and cardiac tamponade,
which is fatal. Internal rupture refers to the interventricular septum and papillary muscles, leading to severe
congestive heart failure. Heart rupture is more common in patients with primary myocardial infarction.

№ 13. Macrofocal postinfarction cardiosclerosis.

On the section of the left ventricular wall, is observed, an area of fibroconjunctive tissue (scar), white in
colour, with a cartilaginous appearance, hard in consistency, the ventricular wall is hypertrophied.

Macrofocal cardiosclerosis is the consequence of myocardial infarction, it occurs after the organization of
the infarct area, which occurs within 6-7 weeks from the onset of the disease. Calcium salts can be stored in
the area of the post-infarct scar, compensatory hypertrophy is observed in the adjacent heart muscle. Possible
complications: congestive heart failure, rhythm and conductibility disorders, chronic heart aneurysm. In the
International Classification of Diseases it is called "Old myocardial infarction".
№ 24. Heart rupture (left ventricle) in acute myocardial infarction.
№ 13. Macrofocal postinfarction cardiosclerosis.
№ 18. Cardiac thrombosis.
On the cross section of the heart are observed massive wall thrombi, which adhere closely to the parietal endocardium,
brown in color, dense consistency, dry appearance, thickness up to 1 cm.

Intracardiac thrombosis is found in several diseases, in which inflammation of the parietal endocardium occurs. It is
observed in rheumatic parietal endocarditis, transmural or subendocardial myocardial infarction, cardiomyopathies.
Thrombosis of the left atrium occurs in mitral stenosis, and of the right atrium-in chronic congestive heart failure. An
important causal factor is atrial fibrillation. Left intracardiac thrombosis can lead to thromboembolism of the arteries of
great circulation with infarcts in the brain, spleen, kidneys, gangrene of the extremities or intestines, and thrombosis of
the right heart cavities - to pulmonary infarctions or thromboembolism of the common trunk of the pulmonary artery.

№ 16. Verrucous acute endocarditis.

On the atrial surface of the mitral valve cusps there are fine thrombotic deposits (warts), brown in color, dense in
consistency, which adhere closely to the valvular endocardium, located mainly on the free edge, closing the cusps; the
cusps are thickened, deformed, the tendon cords also are thickened and fused.

Valvular endocarditis is a manifestation of rheumatic carditis. More frequently is affected mitral valve (~ 70%):
concomitant mitral and aortic valve involvement occurs in (~ 25%), the tricuspid valve is less commonly involved, and
the aortic valve is about (2%), and the pulmonary valve is practically not affected. Acute valvulitis develops on free
valves, is manifested by fibrinoid necrosis, inflammatory cellular infiltration, Aschoff granulomas, fibrin deposits in the
form of warts with a diameter of 1-2 mm, arranged in a string along the closing edges of the valves , usually on the atrial
surface of the atrioventricular valves and on the ventricular surfaces of the crescent valves, in the occurrence of these
lesions reflects the role of the mechanical and hemodynamic factor. Chronic valvulitis is manifested by the organization
of acute inflammation and fibrinous warts, the appearance of new, larger warts on the already deformed, thickened
valves, sclerosis and retraction, shortening of the cusps and crescent leaves, their concretion, calcinosis. At the same
time, the mitral valve become more thick, shorten and fuse the tendon cords, which together with the concretion of the
cusps leads to the installation of a mitral stenosis with the appearance of a "fish mouth" or "buttonhole". The functional
consequences consist of valvular insufficiency or stenosis and the gradual development of congestive heart failure.
№ 18. Cardiac thrombosis.
№ 16. Verrucous acute endocarditis.
№ 6. Rheumatic mitral valvulopathy.

The cusps of the mitral valve are deformed, thickened, sclerosed, overgrown with each other, of dense
consistency, the mitral orifice is stenotic, has the shape of a "fish mouth" or "buttonhole", the wall of the left
ventricle is hypertrophied.

Most of the acquired valvulopathies - more than 80% - are of rheumatic origin. The heart valves are
deformed, sclerosed, have a dense consistency, lose elasticity and mobility, sometimes they are overgrown.
Microscopically, is observed sclerosis and hyalinosis of the valvular tissue, its vascularization and
calcinosis. Clinical-anatomical variants of valvulopathies are valvular insufficiency, when the cusps or
crescent leaves do not close the valvular orifice and valvular stenosis, when the orifice does not open
completely: are common combined valvulopathies, when the association of valvular insufficiency and
stenosis occurs with the predominance of one of this. These changes in the heart valves are a consequence
of valvular endocarditis. In addition to rheumatism valvulopathies are found in atherosclerosis, especially
aortic valvulopathy, tertiary syphilis - aortic valve insufficiency; in some diseases can develop relative
insufficiency of the heart valves due to dilation of the fibrous ring of the valves but they remain intact, for
example in dilatative cardiomyopathy. Cardiac valvulopathy leads to progressive chronic congestive heart
failure.
№ 6. Rheumatic mitral valvulopathy.
№ 11. Fibrinous pericarditis.
The epicardium is opaque, the surface irregular, covered with yellowish-white deposits of fibrin in the form
of villi, which occur due to contractile movements, the heart has a hairy appearance or "cat tongue" (villous
heart).

Fibrinous pericarditis is found in rheumatism, tuberculosis, transmural myocardial infarction, uremia, etc.
On auscultation it is manifested by a breath of pericardial rubbing. Consequences: resorption of fibrinous
exudate or its organization with the formation of adhesions between the pericardial sheets and obliteration of
the pericardial sac. Over time, calcium salts are deposited in the sclerotic pericardium and the "armor heart"
appears, which is clinically manifested by chronic congestive heart failure.

№ 8. Round thrombus in left atrium.

The left atrium of the heart is dilated, a spherical thrombus is present in the cavity, diameter ~ 5-6 cm,
smooth, glossy surface, dense consistency, is free in the atrial cavity, does not adhere to the wall, the mitral
valve is stenotic.

Spherical thrombus in the left atrium of the heart is very rare, more commonly seen in mitral stenosis with
dilated atrium and turbulent, rotating blood circulation, which promotes the formation and increase in size of
the thrombus, which gradually acquires a spherical appearance. The spherical thrombus in the left atrium
can lead to sudden death.
№ 11. Fibrinous pericarditis.
№ 8. Round thrombus in left atrium.
Scheme of the evolution and complications of coronary atherosclerosis.
Coronary atherosclerosis, intramural hemorrhage.
Stenosing coronary atherosclerosis.
Coronary thrombosis.
Leukocyte infiltration in the area of heart rupture.
Hemopericardium.
Chronic postinfarction cardiac
aneurysm.
Regenerative myocardial hypertrophy.
Hypertrophic cardiomyopathy.
Restrictive cardiomyopathy (endomyocardial fibrosis).
 Mucoid intumescence
of the endocardium and arterial wall
in rheumatic fever
(metachromasia of connective tissue
with toluidine blue staining)
Fibrinoid necrosis of connective tissue.
Chronic verrucous valvular
endocarditis.
Mitral stenosis (view from left atrium).
Aortic stenosis.
 THE HEART
• Normal
• Pathology
– Heart Failure: L, R
– Heart Disease
• Congenital: LR shunts, RL shunts, Obstrustive
• Ischemic: Angina, Infarction, Chronic Ischemia, Sudden Death
• Hypertensive: Left sided, Right sided
• Valvular: AS, MVP, Rheumatic, Infective, Non-Infective, Carcinoid,
Artificial Valves
• Cardiomyopathy: Dilated, Hypertrophic, Restrictive, Myocarditis,
Other
• Pericardium: Effusions, Pericarditis
• Tumors: Primary, Effects of Other Primaries
• Transplants
 NORMAL Features
• 6000 L/day
• 250-300 grams
• 40% of all deaths (2x cancer)
• Wall thickness ~ pressure
• (i.e., a wall is only as thick as it has to be)
– LV=1.5 cm
– RV= 0.5 cm
– Atria =.2 cm
• Systole/Diastole
• Starling’s Law
 TERMS
• CARDIOMEGALY
• DILATATION, any chamber, or all
• HYPERTROPHY, and chamber, or all
STRIATIONS

NUCLEUS

DISCS

SARCOLEMMA

SARC. RETIC.

MITOCHONDRIA

ENDOTHELIUM

FIBROBLASTS

GLYCOGEN

A.N.P.
S.A. NodeAV NodeBundle of HIS L. Bundle, R. Bundle
Anterior
Lateral
Posterior
Septal
 VALVES
• AV:
– TRICUSPID
– MITRAL
• SEMILUNAR:
– PULMONIC
– AORTIC
 CARDIAC AGING
Epicardial Coronary
Chambers Arteries
Increased left atrial cavity size Tortuosity
Decreased left ventricular Increased cross-sectional
cavity size
Sigmoid-shaped ventricular luminal
Calcific area
deposits
septum Atherosclerotic plaque
Myocardium
Valves Increased mass
Increased subepicardial
Aortic valve calcific deposits fat
Mitral valve annular calcific deposits Brown atrophy
Lipofuscin deposition
Fibrous thickening of leaflets
Basophilic
Buckling of mitral leaflets toward
degeneration
Amyloid deposits
 CARDIAC AGING
Aorta
Dilated ascending aorta with rightward shift

Elongated (tortuous) thoracic aorta

Sinotubular junction calcific deposits

Elastic fragmentation and collagen accumulation

Atherosclerotic plaque
BROWN
ATROPHY, HEART

LIPOFUCSIN
 Pathologic Pump Possibilities
• Primary myocardial failure (MYOPATHY)
• Obstruction to flow (VALVE)
• Regurgitant flow (VALVE)
• Conduction disorders (CONDUCTION
SYSTEM)
• Failure to contain blood (WALL
INTEGRITY)
• DEFINITION
CHF
• TRIAD
– 1) TACHYCARDIA
– 2) DYSPNEA
– 3) EDEMA
• FAILURE of Frank Starling mechanism
• HUMORAL FACTORS
– Catecholamines (nor-epinephrine)
– ReninAngiotensionAldosterone
– Atrial Natriuretic Polypeptide (ANP)
• HYPERTROPHY and DILATATION
 HYPERTROPHY
• PRESSURE OVERLOAD (CONCENTRIC)
• VOLUME OVERLOAD (CHF)

• LVH, RVH, atrial, etc.

• 2X normal weight ischemia

• 3X normal weight HTN
• >3X normal weightMYOPATHY, aortic
regurgitation
 CHF: Autopsy Findings
• Cardiomegaly
• Chamber Dilatation
• Hypertrophy of myocardial fibers,
BOXCAR nuclei
 Left Sided Failure
• Low output vs. congestion
• Lungs
– pulmonary congestion and edema
– heart failure cells
• Kidneys
– pre-renal azotemia
– salt and fluid retention
• renin-aldosterone activation
• natriuretic peptides
• Brain: Irritability, decreased attention,
stuporcoma
 Left Heart Failure Symptoms
• Dyspnea
– on exertion
– at rest
• Orthopnea
– redistribution of peripheral edema fluid
– graded by number of pillows needed
• Paroxysmal Nocturnal Dyspnea (PND)
LEFT Heart Failure
Dyspnea
Orthopnea
PND (Paroxysmal Nocturnal
Dyspnea)
Blood tinged sputum
Cyanosis
Elevated pulmonary
“WEDGE” pressure (PCWP)
 Right Sided Heart Failure
• Etiology
– left heart failure
– cor pulmonale
• Symptoms and signs
– Liver and spleen
• passive congestion (nutmeg liver)
• congestive spleenomegaly
• ascites
– Kidneys
– Pleura/Pericardium
• pleural and pericardial effusions
• transudates
– Peripheral tissues
RIGHT Heart Failure
FATIGUE
“Dependent” edema
JVD
Hepatomegaly (congestion)
ASCITES, PLEURAL EFFUSION
GI
Cyanosis
Increased peripheral venous
pressure (CVP)
 HEART DISEASE
•CONGENITAL (CHD)
• ISCHEMIC (IHD)
• HYPERTENSIVE (HHD)
• VALVULAR (VHD)
• MYOPATHIC (MHD)
 CONGENITAL HEART
DEFECTS
• Faulty embryogenesis (week 3-8)
• Usually MONO-morphic (i.e., SINGLE
lesion) (ASD, VSD, hypo-RV, hypo-LV)
• May not be evident until adult life
(Coarctation, ASD)
• Overall incidence 1% of USA births
• INCREASED simple early detection via
non invasive methods, e.g., US, MRI, CT,
etc.
 Incidence per
Malformation Million Live Births %
Ventricular septal defect 4482 42
Atrial septal defect 1043 10
Pulmonary stenosis 836 8
Patent ductus arteriosus 781 7
Tetralogy of Fallot 577 5
Coarctation of aorta 492 5
Atrioventricular septal defect 396 4
Aortic stenosis 388 4
Transposition of great arteries 388 4
Truncus arteriosus 136 1
Total anomalous pulmonary 120 1
Tricuspid
venous atresia
connection
 GENETICS
• Gene abnormalities in only 10% of CHD
• Trisomies 21, 13, 15, 18, XO
• Mutations of genes which encode for
transcription factorsTBX5ASD,VSD
•  NKX2.5ASD
• Region of chromosome 22 important in heart
development, 22q11.2
deletionconotruncus, branchial arch, face
 ENVIRONMENT
• RUBELLA
• TERATOGENS
 CHD
• LR SHUNTS: all “D’s” in their names
– NO cyanosis
– Pulmonary hypertension
– SIGNIFICANT pulmonary hypertension is
IRREVERSIBLE
• RL SHUNTS: all “T’s” in their names
– CYANOSIS (i,.e., “blue” babies)
– VENOUS EMBOLI become SYSTEMIC
• OBSTRUCTIONS
 LR
NON CYANOTIC
• ASD

• VSD IRREVERSIBLE
PULMONARY
• ASVD HYPERTENSION
• PDA IS THE MOST
FEARED
CONSEQUENCE
 ASD
• NOT patent foramen ovale
• Usually asymptomatic until adulthood
• SECUNDUM (90%): Defective fossa ovalis
• PRIMUM (5%): Next to AV valves, mitral
cleft
• SINUS VENOSUS (5%): Next to SVC
with anomalous pulmonary veins draining
to SVC or RA
 VSD
• By far, most common CHD defect
• Only 30% are isolated
• Often with TETRALOGY of FALLOT
• 90% involve the membranous septum
• If muscular septum is involved, likely to have
multiple holes
• SMALL ones often close spontaneously
• LARGE ones progress to pulmonary
hypertension
 PDA
• 90% isolated
• HARSH, machinery-like murmur
• LR, possibly RL as pulmonary
hypertension approaches systemic pressure
• Closing the defect may be life saving
• Keeping it open may be life saving
(Prostaglandin E). Why?
 AVSD
• Associated with defective,
inadequate AV valves
• Can be partial, or COMPLETE
(ALL 4 CHAMBERS FREELY
COMMUNICATE)
 RL
• Tetralogy of Fallot
• Transposition of great arteries
• Truncus arteriosus
• Total anomalous pulmonary venous
connection
• Tricuspid atresia
 RL SHUNTS
• TETRALOGY of FALLOT most COMMON
– 1) VSD, large
– 2) OBSTRUCTION to RV flow
– 3) Aorta OVERRIDES the VSD
– 4) RVH
– SURVIVAL DEPENDS on SEVERITY of
SUBPULMONIC STENOSIS
– Can be a “PINK” tetrology if pulmonic
obstruction is small, but the greater the obstruction,
the greater is the RL shunt
 TGA (TRANSPOSITION
of GREAT ARTERIES)
• NEEDS a SHUNT for
survival
– PDA or PFO (65%),
“unstable” shunt
– VSD (35%), “stable” shunt
– RV>LV in thickness
– Fatal in first few months
– Surgical “switching”
TRUNCUS ARTERIOSIS
 TRICUSPID ATRESIA
• Hypoplastic RV
• Needs a shunt, ASD, VSD, or PDA
• High mortality
Total Anomalous Pulmonary Venous
Connection (TAPVC)
• PULMONARY VEINS do NOT go into LA,
but into L. innominate v. or coronary sinus
• Needs a PFO or a VSD
• HYPOPLASTIC LA
 OBSTRUCTIVE CHD
• COARCTATION of aorta
• Pulmonary stenosis/atresia
• Aortic stenosis/atresia
 COARCTATION of
AORTA
• M>F
• But XO’s frequently have it
• INFANTILE FORM (proximal to PDA) (SERIOUS)
• ADULT FORM (CLOSED DUCTUS)
• Bicuspid aortic valve 50% of the time
 PULMONIC
STENOSIS/ATRESIA
• If 100% atretic, hypoplastic RV with ASD
• Clinical severity ~ stenosis severity
 AORTIC
STENOSIS/ATRESIA
• VALVULAR
– If severe, hypoplastic LVfatal
• SUB-valvular (subaortic)
– Aortic wall THICK BELOW cusps
• SUPRA-valvular
– Aortic wall THICK ABOVE cusps in ascending
aorta
 HEART DISEASE
• CONGENITAL (CHD)

•ISCHEMIC (IHD)
• HYPERTENSIVE (HHD)
• VALVULAR (VHD)
• MYOPATHIC (MHD)
 SYNDROMES of IHD
• Angina Pectoris: Stable, Unstable
• Myocardial Infarction (MI, AMI)
• Chronic IHD CHF (CIHD)
• Sudden Cardiac Death (SCD)

• “Acute” Coronary Syndromes:

– UNSTABLE ANGINA
– AMI
– SCD (Sudden Cardiac Death)
 IHD RISK
• Number of plaques
• Distribution of plaques
• Size, structure of plaques
ACUTE CORONARY SYNDROMES
• “The acute coronary syndromes are
frequently initiated by an unpredictable
and abrupt conversion of a stable
atherosclerotic plaque to an unstable and
potentially life-threatening
atherothrombotic lesion through
superficial erosion, ulceration, fissuring,
rupture, or deep hemorrhage, usually
with superimposed thrombosis.”
 EPIDEMIOLOGY
• ½ million die of IHD yearly in USA
• 1 million in 1963. Why?
– Prevention of control controllable risk factors
– Earlier, better diagnostic methods
– PTCA, CABG, arrythmia control

• 90% of IHD patients have

ATHEROSCLEROSIS (no surprise here)
 ACUTE CORONARY
SYNDROME FACTORS

• ACUTE PLAQUE CHANGE

*******
• Inflammation
• Thrombus
• Vasoconstriction
******* MOST IMPORTANT
ACUTE PLAQUE CHANGE
• Rupture/Refissuring
• Erosion/Ulceration, exposing ECM
• Acute Hemorrhage

NB: Plaques do NOT have to be severely stenotic to

cause acute changes, i.e., 50% of AMI results from
thromboses of plaques showing LESS THAN 50%
stenosis
 INFLAMMATION
• Endothelial cells release CAMs, selectins
• T-cells release TNF, IL-6, IFN-gamma to
stimulate and activate endothelial cells and
macrophages
• CRP predicts the probability of damage in
angina patients
 THROMBUS
• Total occlusion
• Partial
• Embolization
 VASOCONSTRICTIO
N
• Circulating adrenergic agonists
• Platelet release products
• Endothelially released factors, such as
endothelin
 Coronary Artery Pathology in Ischemic Heart Disease
Plaque-Associated
Plaque
Syndrome Stenoses Disruption Thrombus
Stable angina >75% No No
Unstable Variab Frequent Nonocclusive, often with
angina
Transmural Variab Frequent
le thromboemboli
Occlusive
myocardial le
Subendocardial
infarction Variab Variable Widely variable, may be
myocardial le absent, partial/complete, or
Sudden death
infarction Usuall Frequent Often
lysed small platelet
y aggregates or thrombi and/or
sever thromboemboli
e
 ANGINA PECTORIS
• Paroxysmal (sudden)
• Recurrent
• 15 sec.15 min.
• Reduced perfusion, but NO infarction
• THREE TYPES
– STABLE: relieved by rest or nitro
– PRINZMETAL: SPASM is main feature, responds to
nitro, S-T elevation
– UNSTABLE (crescendo, PRE-infarction, Q-wave
angina): perhaps some thrombosis, perhaps some non
transmural necrosis, perhaps some embolization, but
DISRUPTION of PLAQUE is universally agreed upon
MYOCARDIAL INFARCTION
• Transmural vs. Subendocardial (inner 1/3)
• DUH! EXACT SAME risk factors as atherosclerosis
• Most are TRANSMURAL, and MOST are caused
by coronary artery occlusion
• In the 10% of transmural MIs NOT associated
with atherosclerosis:
– Vasospasm
– Emboli
– UNexplained
 MYOCARDIAL RESPONSE
Feature Time
Onset of ATP depletion Seconds
Loss of contractility <2 min
ATP reduced
to 50% of normal 10 min
to 10% of normal 40 min
Irreversible cell injury 20–40 min
Microvascular injury >1 hr
PROGRESSION OF NECROSIS
 TIMING of Gross and
Microscopic Findings
½–4 hr None Usually none; variable waviness of fibers at border

4–12 hr Occasionally dark mottling Beginning coagulation necrosis; edema; hemorrhage

12–24 hr Dark mottling Ongoing coagulation necrosis; pyknosis of nuclei;

myocyte hypereosinophilia; marginal contraction
band necrosis; beginning neutrophilic infiltrate
1–3 days Mottling with yellow-tan Coagulation necrosis, with loss of nuclei and striations;
infarct center interstitial infiltrate of neutrophils
3–7 days Hyperemic border; central Beginning disintegration of dead myofibers, with dying
yellow-tan softening neutrophils; early phagocytosis of dead cells by
macrophages at infarct border
7–10 Maximally yellow-tan and Well-developed phagocytosis of dead cells; early
days soft, with depressed red- formation of fibrovascular granulation tissue at
tan margins margins
10–14 Red-gray depressed infarct Well-established granulation tissue with new blood
days borders vessels and collagen deposition

2–8 wk Gray-white scar, progressive Increased collagen deposition, with decreased cellularity
from border toward core
of infarct
>2 mo Scarring complete Dense collagenous scar
1 day, 3-4 days, 7 days, weeks,
months
 RE-PERFUSION
• Thrombolysis
• PTCA
• CABG

• Reperfusion CANNOT restore necrotic or

dead fibers, only reversibly injured ones

• REPERFUSION “INJURY”
– Free radicals
– Interleukins
 AMI DIAGNOSIS
• SYMPTOMS
• EKG
• DIAPHORESIS
• (10% of MIs are “SILENT” with Q-waves)
• CKMB gold standard enzyme
• Troponin-I, Troponin-T better
• CRP predicts risk of AMI in angina patients
 COMPLICATIONS
• Wall motion abnormalities
• Arrhythmias
• Rupture (4-5 days)
• Pericarditis
• RV infarction
• Infarct extension
• Mural thrombus
• Ventricular aneurysm
• Papillary muscle dysfunction (regurgitation)
• CHF
 CIHD, aka, ischemic
“cardiomyopathy”
• Progress to CHF often with no
pathologic or clinical evidence of
localized infarction
– Extensive atherosclerosis
– No infarct
– H&D present
 SUDDEN CARDIAC DEATH
• 350,000 in USA yearly from atherosclerosis
• NON-atherosclerotic sudden cardiac death includes:
– Congenital coronary artery disease
– Aortic stenosis
– MVP
– Myocarditis
– Cardiomyopathy (sudden death in young athletes)
– Pulmonary hypertension
– Conduction defects
– HTN, hypertrophy of UNKNOWN etiology
 AUTOPSY findings in SCD
• >75% narrowing of 1-3 vessels
• Healed infarcts 40%

• “ARRHYTHMIA” is often a very

convenient conclusion when no anatomic
findings are present, i.e., “wastebasket”
diagnosis
 HEART DISEASE
• CONGENITAL (CHD)
• ISCHEMIC (IHD)

•HYPERTENSIVE
(HHD)
• VALVULAR (VHD)
• MYOPATHIC (MHD)
 HHD
• DEFINITION:
(Left)
Hypertrophic
adaptive response of the heart, which can
progress:
– Myocardial dysfunction
– Cardiac dilatation
– CHF
– Sudden death
 NEEDED for DIAGNOSIS:
• LVH (LV>2.0 and/or Heart>500 gm.)
• HTN (>140/90)
 PREVALENCE:
• WHAT % of USA people have
hypertension?
 PREVALENCE:
• WHAT % of USA people have
hypertension?

• Answer: 25%
 HISTOPATHOLOG
• INCREASED FIBER
Y (MYOCYTE)
THICKNESS
• INCREASED nuclear size with increased
“blockiness” (boxcar nucleus)
• EKG
CLINICAL
Summary of LVH
Criteria
1) R-I + S-III >25 mm
2) S-V1 + R-V5 >35
mm
3) ST-Ts in left leads
4) R-L >11 mm
ATRIAL FIBRILLATION 5) LAE + other criteria
Why?*
Positive Criteria:
CHF, cardiac dilatation, 1=possible
pulmonary
2=probable 3=definite
venous congestion and dilatation
 COURSE:
• NORMAL longevity, death from
other causes
• Progressive IHD
• Progressive renal damage,
hemorrhagic CVA (Which arteries?)
• CHF
HHD (Right) = COR PULMONALE

• ACUTE: Massive PE
• CHRONIC: COPD, CRPD,
Pulmonary artery disease, chest wall
motion impairment
Diseases of the Pulmonary Disorders Affecting Chest
Parenchyma Movement
Chronic obstructive pulmonary Kyphoscoliosis
disease Marked obesity (pickwickian
Diffuse pulmonary interstitial syndrome)
fibrosis Neuromuscular diseases

Pneumoconioses
Cystic fibrosis
Bronchiectasis

Diseases of the Pulmonary Vessels

Disorders Inducing
Recurrent pulmonary
Pulmonary Arterial
thromboembolism
Constriction
 HEART DISEASE
• CONGENITAL (CHD)
• ISCHEMIC (IHD)
• HYPERTENSIVE (HHD)

•VALVULAR (VHD)
• MYOPATHIC (MHD)
 V HD alvular

• Opening problems: Stenosis

• Closing problems: Regurgitation or
Incompetence
• AS
70% of all VHD
– Calcification of a deformed valve
– “Senile” calcific AS
– Rheum, Heart Dis.

• MS
–Rheumatic Heart Disease
AORTIC STENOSIS
2X gradient pressure
LVH, ischemia
Cardiac decompensation, angina, CHF
50% die in 5 years if angina present
50% die in 2 years if CHF present
 MITRAL ANNULAR
•
CALCIFICATION
Calcification of the
mitral “skeleton”
• Usually NO
dysfunction
• Regurgitation or
Stenosis possible
• F>>M
• ARREGURGITATIONS
– Rheumatic
– Infectious
– Aortic dilatations
• Syphilis
• Rheumatoid Arthritis
• Marfan

• MR
–MVP
– Infectious
– Fen-Phen
– Papillary muscles, chordae tendinae
– Calcification of mitral ring (annulus)
 Mitral Valve Prolapse
(MVP)
• MYXOMATOUS degeneration of
the mitral valve
• Associated with connective tissue
disorders
• “Floppy” valve
• 3% incidence, F>>M
• Easily seen on echocardiogram
MVP: CLINICAL FEATURES
• Usually asymptomatic
• Mid-systolic “click”
• Holosystolic murmur if regurg. present
• Occasional chest pain, dyspnea
• 97% NO untoward effects
• 3% Infective endocarditis, mitral
insufficiency, arrythmias, sudden death
 RHEUMATIC Heart Disease
• Follows a group A strep infection, a few
weeks later
• DECREASE in “developed” countries
• PANCARDITIS
ACUTE:
-Inflammation
-Aschoff bodies
-Anitschkow cells
-Pancarditis
-Vegetations on
chordae tendinae
at leaflet junction
CHRONIC:
THICKENED
VALVES
COMMISURAL
FUSION
THICK, SHORT,
 CLINICAL FEATURES
• Migratory Polyarthritis
• Myocarditis
• Subcutaneous nodules
• Erythema marginatum
• Sydenham chorea
 INFECTIOUS
• Microbes ENDOCARDITIS
– Usually strep viridans
– Often Staph aureus in IVD users
– Enterococci

– HAČEK (normal oral flora)

• Hemophilus influenzae
• Actinobacillus
• Cardiobacterium
• Eikenella
• Kingella
– Fungi, rickettsiae, chlamydia
 INFECTIOUS
• Acute: 50%ENDOCARDITIS
mortality (course=days)
• SUB-acute: LOW mortality (course=weeks)
 VEGETATIONS
• INFECTIVE >5mm
• NON-Infective <5mm
 DIAGNOSIS=MMm, Mmmm, mmmmm

• MAJOR
• Positive blood culture(s) indicating characteristic organism or persistence of unusual organism
• Echocardiographic findings, including valve-related or implant-related mass or abscess, or partial
separation of artificial valve
• New valvular regurgitation

• minor
• Predisposing heart lesion or intravenous drug use
• Fever
• Vascular lesions, including arterial petechiae, subungual/splinter hemorrhages, emboli, septic infarcts,
mycotic aneurysm, intracranial hemorrhage, Janeway lesions
• Immunologic phenomena, including glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
• Microbiologic evidence, including single culture showing uncharacteristic organism
• Echocardiographic findings consistent with but not diagnostic of endocarditis, including new valvular
regurgitation, pericarditis
 NON-infective VEGETATIONS
• <5 mm
• PE
• Trousseau syndrome (migratory
thrombophlebitis with malignancies)
• s/p Swan-Ganz
• Libman-Saks with SLE (both sides of valve)
 Carcinoid Syndrome
• Episodic skin flushing
• Cramps
• Nausea & Vomiting
• Diarrhea

• ↑serotonin, ↑ 5HIAA in urine

• FIBROUS INTIMAL THICKENING
– RV, Tricuspid valve, Pulmonic valve (all RIGHT side)
– Similar to what Fen-Phen does on the LEFT side
 ARTIFICIAL
• MechanicalVALVES
• Xenografts (porcine)

• 60% have complications within 10

years
 HEART DISEASE
• CONGENITAL (CHD)
• ISCHEMIC (IHD)
• HYPERTENSIVE (HHD)
• VALVULAR (VHD)

• MYOPATHIC (MHD)

• PERICARDIAL DISEASE
CARDIOMYOPATHI
• ES
DILATED (DCM)
• Inflammatory – SY-stolic dysfunction
• Immunologic • HYPERTROPHIC
• Metabolic (HCM)
• Dystrophies – DIA-stolic dysfunction
• Genetic • RESTRICTIVE (RCM)
• Idiopathic – DIA-stolic dysfunction
 Indirect
Myocardial
Functional Mechanisms of Dysfunction (Not
Pattern LVEF * Heart Failure Causes Cardiomyopathy)
Dilated <40% Impairment of Idiopathic; alcohol; Ischemic heart
contractility peripartum; genetic; disease; valvular
(systolic myocarditis; heart disease;
dysfunction) hemochromatosis; hypertensive
chronic anemia; heart disease;
doxorubicin congenital heart
(Adriamycin); disease
sarcoidosis
Hypertrop 50–80% Impairment of Genetic; Friedreich Hypertensive
hic compliance ataxia; storage heart disease;
(diastolic diseases; infants of aortic stenosis
dysfunction) diabetic mothers
Restrictive 45–90% Impairment of Idiopathic; Pericardial
compliance amyloidosis; constriction
(diastolic radiation-induced
dysfunction) fibrosis
Cardiac Infections Toxins Metabolic
Viruses Alcohol Hyperthroidism
Chlamydia Cobalt Hypothyroidism
Rickettsia Catecholamines Hyperkalemia
Bacteria Carbon monoxide Hypokalemia
Fungi Lithium Nutritional deficiency (protein,
Protozoa Hydrocarbons thiamine, other avitaminoses)

Arsenic Hemochromatosis

Neuromuscular Cyclophosphamide
Infiltrative
Disease Doxorubicin (Adriamycin)
and daunorubicin Leukemia
Friedreich ataxia
Carcinomatosis
Muscular dystrophy Storage Disorders and Sarcoidosis
Congenital atrophies Other Depositions Radiation-induced
Hunter-Hurler syndrome fibrosis

Immunologic Glycogen storage disease

Myocarditis (several Fabry disease

forms) Amyloidosis
Post-transplant rejection
 DILATED cardiomyopathy
• Chamber thickness (not just LVH)
• Adults
• Progressively declining LVEF
• LVEF ~ prognosis
• 50% die in 2 years
• 3 Main causes
– Myocarditis
– ETOH
– Adriamycin
 DCM

Path:
4 chamber dilatation
Hypertrophy
Interstitial Fibrosis
 Arrhythmogenic Right Ventricular Cardiomyopathy
(Arrhythmogenic Right Ventricular Dysplasia)

This is an uncommon dilated cardiomyopathy

predominantly RIGHT ventricle.

So is NAXOS syndrome.
•
HYPERTROPHIC cardiomyopathy
Also called IHSS, (Idiopathic Hypertrophic
Subaortic Stenosis)
– GENETIC defects involving:
• Beta-myosin heavy chain
• Troponin T
• Alpha-tropomyosin
• Myosin binding protein C
– PATHOLOGY: Massive hypertrophy, Asymmetric
septum, DISARRAY of myocytes, INTERSTITIAL
fibrosis

– CLINICAL: ↓chamber volume, ↓SV, ↓ diastolic

filling
 RESTRICTIVE cardiomyopathy
• (idiopathic)
• ↓ ventricular compliance
• Chiefly affects DIASTOLE
• NORMAL chamber size and wall thickness
• THREE similar diseases affecting predominantly
the SUBENDOCARDIAL area:
– Endomyocardial Fibrosis (African children)
– Loeffler Endomyocarditis (eosinophilic leukemia)
– Endocardial Fibroelastosis (infants)
MYOCARDITIS
• INFLAMMATION of MYOCARDIUM
• Chiefly microbial
– COXACKIE A & B, CMV, HIV
– Trypanosoma cruzi (Chagas dis.), 80%
– Trichinosis
– Toxoplasmosis
– Lyme disease (5%)
– Diphtheria
• IMMUNE: Post-viral, rheumatic, SLE, drug
hypersensitivityalpha-methyl dopa, sulfas
LYMPHOCYTIC INFILTRATES are the USUAL pattern of ALL
myocarditis, but eosinophils, giant cells, and even
 OTHER Myocarditides
• Adriamycin
• Cyclophosphamide
• Catecholamines (Pheochromocytomas)
• Amyloid, systemic or primary cardiac
– Congo red stain: green birefringence with polarization
• Amyloid, aging
– Congo red stain: green birefringence with polarization
• Hemochromatosis (Prussian Blue)
• BOTH HYPER-, HYPO- -thyroidism
 PERICARDIUM
• Normally 30-50 ml clear serous fluid
– Visceral (epicardium)
– Parietal (Fibrous pericardium)

– PERICARDIAL EFFUSIONS TAMPONADE

• Ruptured MI
• Traumatic perforation
• Infective endocarditis
• Ruptured aortic dissection
 PERICARDITIS
• SEROUS : Rheum. Fever (RF), SLE, scleroderma,
tumors, uremia
• FIBRINOUS: MI (Dressler), uremia, radiation,
RF, SLE, s/p open heart surgery
• PURULENT: infective, bacterial
• HEMORRHAGIC: Malignancy, TB
• CASEOUS: TB
• CHRONIC: (ADHESIVE, CONSTRICTIVE)
 TUMORS
• 90% benign “mesenchymal”, i.e., stromal
– MYXOMAS (LEFT ATRIUM
MOST COMMON)
– FIBROMAS
– LIPOMAS
– FIBROELASTOMAS
– RHABDOMYOMA (Most common cardiac tumor
in children)
• 10% SARCOMAS
MYXOMA
 Cardiac effects of NON-cardiac tumors
• Direct Consequences of Tumor
– Pericardial and myocardial metastases
– Large vessel obstruction
– Pulmonary tumor emboli
• Indirect Consequences of Tumor (Complications of
Circulating Mediators)
– Nonbacterial thrombotic endocarditis (NBTE)
– Carcinoid heart disease
– Pheochromocytoma-associated heart disease
– Myeloma-associated amyloidosis
• Effects of Tumor Therapy
– Chemotherapy
– Radiation therapy
 CARDIAC TRANSPLANT
PATHOLOGY
• Most patients are on
immunosuppressives
• 5 year survival >60%
CARDIAC TRANSPLANT
PATHOLOGY