3. Introduction: CHD
• Faulty embryogenesis during 3-8 gestational weeks
• Usually single lesion e.g. ASD, VSD
• May be symptomatic in adult life (Coarctation, ASD)
• Severe anomalies are incompatible with intrauterine survival
• Early detection via US, MRI, CT, etc.
• Associated extra-cardiac abnormalities in a quarter of infants with
CHD
4. Incidence CHD
• 1% of live birth
• Higher in premature infants & stillborns
• 12 disorders account for about 85% of cases
• The risk in the siblings of affected individuals varies
e.g., 2% for coarctation of aorta, 2% & 6-10% for a child
of father & mother with VSD respectively
5. Malformation Incidence per 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 venous connection
120 1
Tricuspid atresia
118 1
Hoffman JIE, Kaplan S: The incidence of congenital heart disease. J Am Coll Cardiol
39:1890, 2002. D = LR shunt, T= RL shunt
6. Etiology & pathogenesis: CHD
• 80% unknown
• Gene abnormalities (10%)
• Trisomies 21, 13, 15, 18, XO
• Trisomy 21 => 40%; high incidence of ASD or VSD or PDA
• XO => coarctation of aorta
• Mutations of genes which encode for transcription factors TBX5ASD,VSD;
NKX2.5ASD
• Environment factors (10%): Rubella, gestational diabetes, teratogens
(thalidomide) & alcohol abuse
7. Morphology: CHD
• Shunts: LR or RL
• Obstruction: abnormal narrowing of chambers, valves, or blood
vessels e.g. Pulmonic stenosis (PS), Aortic stenosis (AS), Coarctation
of the aorta
• Complete obstruction is called atresia e.g. tricuspid atresia
8. Cyanosis
• bluish or purplish tinge to the skin & mucous membranes (un-
oxygenated blood is bypassing the lungs)
• Long standing cyanosis => clubbing of the tips of the fingers & toes
(hypertrophic osteoarthropathy) & polycythemia
11. Acyanotic CHD
• L R Shunts
• ASD, VSD, AVSD, PDA: all “D’s” in their names
• NO cyanosis
• Expose the pulmonary circulation to ↑ pressure &/or volume =>
Pulmonary hypertension (≥ 25 mmHg)
• Significant pulmonary hypertension is irreversible & the most
feared Consequence
12. Cyanotic CHD
• R L Shunts
• Tetralogy of Fallot, Transposition of great arteries, Truncus
arteriosus, Total anomalous pulmonary venous connection,
Tricuspid atresia: : all “T’s” in their names
• Paradoxical embolism:
DVT bypass the lungs & enter systemic
circulation => Brain infarction
13. Left to right shunt
Eisenmenger syndrome (late cyanosis)
irreversible obstructive intimal lesions
exacerbates the ↑ pulmonary resistance reversing the shunt to Right to Left with
unoxygenated blood in the systemic circulation
↑ Pulmonary blood flow &/or pressure
Pulmonary medial hypertrophy & vasoconstriction
15. Atrial septal defect (ASD)
• Not same as probe patent foramen
ovale
• 10% of all CHD, usually isolated,
asymptomatic until adulthood
(>30yrs)
1. Secundum: at the fossa ovalis
(FO), 90%
2. Primum: adjacent to AV valve,
mitral cleft, 25% Down
sydrome
3. Sinus venosus: near the entrance
of SVC, associated with pulmonary
veins draining to SVC or RA &
least common
17. Atrial septal defect (ASD)
• ↑ Pulmonary blood flow => volume hypertrophy of the rt.
atrium & rt. Ventricle => rt. Heart failure
• If defect is small (<2mm) will usually resolves spontaneously
• Closure is performed electively between ages 2 & 5 yrs to
avoid late complications
• Once Eisenmenger syndrome occurs this is considered too
late
19. Ventricular septal defect (VSD)
• Most common CHD, 20-30% isolated
• Types: membranous, infundibular , muscular &
AVSD(asymptomatic)
• 90% involve the membranous
• Symptom is dependent on size
• Small (3-6mm) VSD are usually asymptomatic & 50% will close
spontaneously by age 2yrs
• Muscular close sooner than membranous
• Large ones progress to pulmonary hypertension =>
Eisenmenger syndrome
22. Patent ductus arteriousus (PDA)
o Persistence of the normal fetal
vessel that joins the pulmonary
artery to the Aorta
o 90% isolated; variable length &
diameter
o lately Eisenmenger syndrome
o Keeping it open (Pg E1) may be
life saving in pulmonary or
systemic outflow obstruction such
as TGA, TA, TAPVC
24. Atrioventricular septal defect (AVSD)
results from incomplete fusion of the endocardial cushions
Associated with defective AV valves
1. Partial : priumum ASD & a cleft anterior mitral leaflet causing
mitral insufficiency
2. Complete : large combined AV septal defect & common AV valve:
all 4 chambers freely communicate; >1/3 have down syndrome
25. Tetralogy of Fallot
• most common cyanotic lesion; 4 features
1. VSD, large
2. Subpulmonary stenosis (obstruction to RV flow)
3. Aorta overrides the VSD (receives blood from both
ventricles)
4. Right ventricular hypertrophy
• Survival depends on severity of subpulmonary
stenosis; mild => pink tetralogy; severe =>
cyanosis
• Heart enlarged “boot-shaped” due to rt. Ventricular
hypertrophy, rt. heart failure & infective
endocarditis
26. TGA (TRANSPOSITION of GREAT ARTERIES)
• Aorta (lies anterior & to the right of the pulmonary artery) arises from right
ventricle & pulmonary artery emanates from the left ventricle
• Needs a shunt for survival
• TGA with PDA or foramen ovale (65%) => unstable shunts that tend to close &
require immediate intervention to create new shunt
• TGA with VSD (35%) => stable shunt
• Right ventricular hypertrophy (b/c function as systemic ventricle), left
ventricular atrophy (b/c it supports low resistance pulmonary circulation)
•Without surgery most die within the first
few months of life
31. Total Anomalous Pulmonary Venous
Connection (TAPVC)
• Pulmonary veins do NOT go into LA, but into L. innominate vein or
coronary sinus
• Needs a PFO or a VSD
• HYPOPLASTIC Left atrium
32. Coarctation of the aorta
• narrowing or constriction of the aorta
• M>F (2:1); bicuspid aortic valve in >50%
• Associated with Turner syndrome
• Two forms
1. Infantile:- proximal to a PDA & symptomatic in early childhood
2. Adult:- opposite to the closed ductus arteriosus, distal to the arch
vessels
34. Coarctation of the aorta
Region of the narrowing
(turbulence) => atherosclerosis
35. Clinical manifestation Coarctation of the
aorta
• Depends on the severity of the narrowing & the patency of the ductus
arteriosus
• With PDA: cyanosis (delivery of unsaturated blood through the PDA) of
lower half of the body, often don't survive post-neonatal life
• Without PDA:
– hypertension in upper limbs & head, weak pulses, hypotension in
the lower extremities (caludication & coldness)
– Renal hypoperfusion => renin-angiotensin-aldosterone=>
hypertension=> cardiomegaly
– Rib (3&4) erosion by dilated tortuous intercostal arteries
36. Coarctation of the Aorta
• Cause of death if not treated
• Rupture of dissecting aortic aneurysm,
endocarditis, hypertension
(intracerebral hemorrhage), congestive
heart failure
Rib notching
37. • Pulmonary Stenosis
• Valvular or subpulmonary ventricular
outflow tract
• Most isolated lesions
• If 100% atretic, hypoplastic RV with
ASD
• Clinical severity depends on stenosis
severity
• Aortic stenosis
• Valvular, subvalvular or supravalvular
• VALVULAR: most common
• If severe, hypoplastic LVfatal
38. Congenital Heart Disease
Type of Defect Mechanism
Ventricular Septal
Defect (VSD)
There is a hole within the membranous or muscular portions of the
intraventricular septum that produces a left-to-right shunt, more
severe with larger defects
Atrial Septal Defect
(ASD)
A hole from a septum secundum or septum primum defect in the
interatrial septum produces a modest left-to-right shunt
Patent Ductus
Arteriosus (PDA)
The ductus arteriosus, which normally closes soon after birth,
remains open, and a left-to-right shunt develops
Tetralogy of Fallot
Pulmonic stenosis results in right ventricular hypertrophy and a right-
to-left shunt across a VSD, which also has an overriding aorta
Transposition of
Great Vessels
The aorta arises from the right ventricle and the pulmonic trunk from
the left ventricle. A VSD, or ASD with PDA, is needed for extrauterine
survival. There is right-to-left shunting.
Truncus Arteriosus
There is incomplete separation of the aortic and pulmonary outflows,
along with VSD, which allows mixing of oxygenated and
deoxygenated blood and right-to-left shunting
Hypoplastic Left
Heart Syndrome
There are varying degrees of hypoplasia or atresia of the aortic and
mitral valves, along with a small to absent left ventricular chamber
Coarctation of
Aorta
Either just proximal (infantile form) or just distal (adult form) to the
ductus is a narrowing of the aortic lumen, leading to outflow
obstruction
Total Anomalous
Pulmonary Venous
Return (TAPVR)
The pulmonary veins do not directly connect to the left atrium, but
drain into left innominate vein, coronary sinus, or some other site,
leading to possible mixing of blood and right-sided overload
40. Cardiomyopathy
• Dysfunction of the myocardium itself
• Abnormalities in cardiac wall thickness & chamber size, &
mechanical &/or electrical dysfunction
• Ischemic, valvular & hypertensive heart diseases should be excluded
41. Cardiomyopathy: categories
Three clinical, functional, & pathologic categories
1. Dilated cardiomyopathy (DCM): most common, 90%
2. Hypertrophic cardiomyopathy (HCM)
3. Restrictive (RCM): least common
• idiopathic or specific cause
• Endomyocardial biopsies are used for Dx
42.
43. Dilated cardiomyopathy (DCM)
• “Congestive cardiomyopathy”
• Progressive cardiac dilation & contractile (systolic) dysfunction with
hypertrophy
• Heart enlarged weighing 2-3x normal, & flabby due to dilation of all
chambers, variable ventricular thickness, mural thrombi
• Histology is nonspecific
44. Chest x-ray with cardiomegaly
the left heart edge appearing far to the left
45. DCM
• biventricular dilation of the heart & a
thrombus at the apex of the left ventricle
• large heart with a globoid shape b/c all of
the chambers are dilated
48. Clinical features of DCM
• Any age but common 20-50yrs
• Slowly progressive signs & symptoms of CHF
• 50% of patients die within 2yrs 20 to cardiac failure or arrhythmia
49. Arrhythmogenic Rt. Ventricular cardiomyopathy
(Arrhythmogenic Rt. Ventricular Dysplasia)
• Autosomal dominant
• defective cell adhesion proteins in the desmosomes that link adjacent
cardiac myocytes
• Causes Rt-sided heart failure & various rhythm disturbance
• Rt. Ventricular wall thinned due to loss of myocytes with extensive
fatty infiltration & interstitial fibrosis
51. Hypertrophic cardiomyopathy (HCM)
• Myocardial hypertrophy, abnormal diastolic filling & in 1/3 of cases
intermittent ventricular outflow obstruction
• Mutation in genes encoding sarcomeric proteins
• Heart is thick-walled, heavy, & hypercontracting
• cf. flabby hypocontracting heart of DCM
• Diastolic dysfunction, systolic function preserved
• DDx: HHD, Amyloidosis, aortic stenosis
52. Morphology of HCM
• Massive myocardial hypertrophy without ventricular dilation,
asymmetrical septal hypertrophy
• Mic:
• myocyte hypertrophy (>40µm, normal 15µm)
•haphazard disarray of bundles of myocytes (myofiber
disarray)
• interstitial fibrosis
53. Pathogenesis of HCM
• Mutation in genes that encode proteins for the sarcomere
• cf. DCM is mostly associated with abnormalities of cytoskeleton
• Most autosomal dominant
59. Restrictive cardiomyopathy
• Decrease in ventricular compliance
• resulting in impaired ventricular filling during diastole
• systolic function of the left ventricle is usually unaffected
• DDx: constrictive pericarditis, HCM
60. Restrictive cardiomypathy
• Causes
• Idiopathic or 20 radiation fibrosis, amyloidosis,
sarcoidosis, metastatic tumors, or inborn errors of
metabolism
• Morphology
• Normal sized or slightly enlarged ventricles, the cavities are not dilated
• Myocardium is firm, noncompliant, biatrial dilation
• Mic: interstitial fibrosis; disease specific features
61. systemic amyloidosis or senile cardiac
amyloidosis
•Congo red apple green birefringence
Cardiac amyloidosis
Amyloid appearing as amorphous pink
material around myocytes
66. Cardiomyopathies
Type of CMP Findings
Dilated
(Congestive)
All four chambers are dilated, and
there is also hypertrophy. The most
common cause is chronic alcoholism,
though some may be the end-stage of
remote viral myocarditis.
Hypertrophic
The most common form, idiopathic
hypertrophic subaortic stenosis
(IHSS) results from asymmetric
interventricular septal hypertrophy,
resulting in left ventricular outflow
obstruction.
Restrictive
The myocardium is infiltrated with a
material that results in impaired
ventricular filling. The most common
causes are amyloidosis and
hemochromatosis.
67. Myocarditis
oInflammation of the myocardium that result in injury to the
cardiac myocytes
oThe inflammatory process is the cause of rather than a response to
myocardial injury
• Asymptomatic => heart failure or arrhythmias
68. Causes: myocarditis
1. Infections
• Viruses: coxackieviruses A & B, HIV, CMV, etc
• Bacteria: C. diphtheriae, Borrelia
• Fungi: Candida
• Protozoa: Toxoplamosis, T. cruzi (Chagas disease)
• Helminthes: trichinosis
• Rickettsiae & Chlamydiae
2. Immune mediated e.g. RF, drug (methyldopa,
sulfonamides) hypersensitivity, SLE, postviral
3. Ionizing radiation
4. Unknown e.g. sarcoidosis, giant cell myocarditis
76. • Normal coronary artery
• Coronary atherosclerosis
Narrowing of the lumen e to
atherosclerotic plaque
Angiography coronary
atherosclerosis
77. Syndromes of IHD
1. Angina Pectoris
2. Myocardial Infarction (MI, AMI)
3. Chronic IHD with heart failure
4. Sudden Cardiac Death (SCD)
Syndromes of IHD are late manifestation of coronary
atherosclerosis
78. Acute coronary syndromes
• Unstable angina, MI and sudden death
• initiated by an unpredictable & abrupt conversion of a stable atherosclerotic
plaque to an unstable
• Vulnerable plaques: large areas of foam cells & extracellular lipid, thin fibrous
caps, few smooth muscle cells or clusters of inflammatory cells
• Rupture, erosion, ulceration, fissuring, or deep hemorrhage => superimposed
thrombosis => partial or complete occlusion called plaque disruption or plaque
change
• Plaques do NOT have to be severely stenotic to cause plagure changes (50% of
MI results from thromboses of plaques showing < 50% stenosis)
82. Chronic plaque with thrombosis = Acute coronary
syndromes
Atherosclerotic plaque rupture (arrow points to the site of plaque rupture)
A, Plaque rupture without superimposed thrombus
B, Acute coronary thrombosis superimposed on an atherosclerotic plaque
83. Angina pectoris (chest pain)
• Paroxysmal & usually recurrent attacks of substernal or precordial
chest discomfort
• Constricting, squeezing, choking or knifelike
• Transient (15’- 15 min) myocardial ischemia but no infarction
• Three patterns: STABLE, UNSTABLE, PRINZMETAL
84. Stable (typical) angina
• most common
• Imbalance in perfusion & relative to myocardial demand
• produced by exercise or stress (emotional excitement)
• relieved by rest (↓ demand) or nitroglycerin (vasodilator =>
increases perfusion)
85. Unstable (crescendo) angina
prolonged pain precipitated by lower levels of exercise or even at
rest
Caused by disruption of an atherosclerotic plaque with
superimposed partial thrombosis & possibly embolization or
vasospasm (or both)
Serves as warning that acute MI may be imminent (pre-infarction
angina)
Q-wave angina
86. Prinzmetal (vasoplastic) angina
• Uncommon
• episodic myocardial ischemia that is caused by coronary
artery spasm
• occurs at rest & unrelated to physical activity, heart rate, or BP
• responds to vasodilators & Ca channel blockers
• ST segment elevation
87. Myocardial infarction (MI)
aka heart attack
• Necrosis of cardiac muscle due to prolonged severe ischemia
• increases with ↑ age & when risk factors to atherosclerosis (DM, smoking,
hypertension, etc) are present; M>F
• Transmural vs Subendocardial (inner 1/3 or 1/2 of ventricular wall)
• Most are TRANSMURAL, and MOST are caused by coronary artery occlusion
• In the 10% of transmural MIs occurs in the absence of the typical coronary
vascular pathology,
•Vasospasm, Emboli, vasculitis, amyloidosis, sickle
cell anemia, etc
88. Pathogenesis of MI
• Disruption (hemorrhage, erosion, rupture, etc) of atheromatous
plaque =>
• exposed to subendothelial collagen & necrotic plaque content =>
platelets activation & microthombi =>
• vasospasm (mediators released from platelets) =>
• tissue factor activates the coagulation pathway => additional
thrombus => completely occlude the lumen of vessel (within
minutes)
89. Approximate time of onset of key events in ischemic cardiac
myocytes
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
ATP, adenosinde phosphate
90. Temporal sequence of early biochemical findings & progression of
necrosis after onset of severe myocardial ischemia
Necrosis complete within 6hrs of the onset of severe myocardial ischemia
Early (1st 4hrs) reperfusion can prevent cell death
93. Frequencies & the corresponding sites of MI
• LAD coronary artery (40-50%) (left coronary artery)
• Anterior wall of LV near the apex, anterior 2/3rd septum, & the apex
• RCA (30-40%) ( right coronary artery)
• Postero-basal wall of the LV; posterior third ventricular septum &
inferior/posterior RV free wall in some
• LCX (15-20%) (left circumflex artery)
• => lateral wall of lt. ventricle except apex
94. Distribution of myocardial ischemic necrosis correlated with the location
& nature of decreased perfusion
95. Dense collagenous scar
Scarring complete
>2 mo
Increased collagen deposition, with decreased cellularity
Gray-white scar, progressive
from border toward core
of infarct
2–8 wk
Well-established granulation tissue with new blood
vessels and collagen deposition
Red-gray depressed infarct
borders
10–14
days
Well-developed phagocytosis of dead cells; early
formation of fibrovascular granulation tissue at
margins
Maximally yellow-tan and
soft, with depressed red-
tan margins
7–10
days
Beginning disintegration of dead myofibers, with dying
neutrophils; early phagocytosis of dead cells by
macrophages at infarct border
Hyperemic border; central
yellow-tan softening
3–7 days
Coagulation necrosis, with loss of nuclei and striations;
interstitial infiltrate of neutrophils
Mottling with yellow-tan
infarct center
1–3 days
Ongoing coagulation necrosis; pyknosis of nuclei;
myocyte hypereosinophilia; marginal contraction
band necrosis; beginning neutrophilic infiltrate
Dark mottling
12–24 hr
Beginning coagulation necrosis; edema; hemorrhage
Occasionally dark mottling
4–12 hr
Usually none; variable waviness of fibers at border
None
½–4 hr
Gross Microscopic
Evolution of morphologic changes in MI
96. Acute myocardial infarct, predominantly of the posterolateral left ventricle,
demonstrated histochemically by a lack of staining by triphenyltetrazolium chloride in
areas of necrosis (arrow). The staining defect is due to the enzyme (dehydrogensae)
leakage that follows cell death. Note the myocardial hemorrhage at one edge of the
infarct that was associated with cardiac rupture, and the anterior scar (arrowhead),
indicative of old infarct. Specimen is oriented with the posterior wall at the top.
97. Fresh myocardial infarction (arrows)
in the anterior portion of the LV and extending into the anterior portion of the interventricular
septum.
Note that the walls of the LV & RV are slightly thicker than normal.
98. Large recent myocardial infarction
• Infarct appears yellow-tan surrounded by a zone of red hyperemia.
Remaining viable myocardium is reddish- brown
105. Reperfusion often contain contraction bands
• intensely eosinophilic intracellular “stripes” due to exaggerated
contraction of myofibrils (calcium ions from the plasma)
106. MI diagnosis
Clinical symptoms
Electrocardiogram (ECG):
Q-waves, T-wave inversion, & ST-T elevation
Myocardial proteins in the plasma
Cardiac troponins T & I: most sensitive & specific, persists for 7-10days
Creatine kinase (CK-MB)
10-15% “Silent” or asymptomatic
107. Electrocardiogram (ECG)
• Q waves & elevated ST segments in
the anterior chest leads V2-V5
• Normal for comparison
114. MI contd.
• Postinfarct complications & the prognosis depend on the infarct size,
location, & thickness (subendocardial or transmural)
• Noninfarcted segments of the ventricle undergo hypertrophy &
dilation => ventricular remodeling
115. Chronic ischemic heart disease (CIHD)
• Progressive heart failure as a consequence of ischemic myocardial
damage
• In most there has been prior MI
• Due to the functional decompensation of hypertrophied noninfarcted
myocardium
• enlarged & heavy heart 20 to lt. ventricular hypertrophy & dilation;
stenosing coronary atherosclerosis; scars of healed infarct
116. Sudden cardiac death (SCD)
• Defn: unexpected death from cardiac causes in individuals without
symptomatic heart disease or early after symptom onset (within 1hr)
• Consequences of a lethal arrhythmias (asystole, ventricular fibrillation)
• Coronary atherosclerosis (>75% stenosis) in 80-90%
• NON-atherosclerotic SCD (10-20%): congenital coronary artery disease, aortic
valve stenosis, mitral valve prolapse, myocarditis, dilated or hypertrophy
cardiomyopathy, pulmonary hypertension, conduction defects, cardiac
hypertrophy of any cause (hypertension), etc.
117. Often small platelet aggregates or thrombi
and/or thromboemboli
Frequent
Usually
severe
Sudden death
Widely variable, may be absent,
partial/complete, or lysed
Variable
Variable
Subendocardial
myocardial infarction
Occlusive
Frequent
Variable
Transmural
myocardial infarction
Nonocclusive, often with thromboemboli
Frequent
Variable
Unstable angina
No
No
>75%
Stable angina
Plaque-Associated Thrombus
Plaque
Disruption
Stenoses
Syndrome
Coronary Artery Pathology in Ischemic Heart Disease
126. Chronic or Healed Pericarditis
• Adhesive mediastinopericarditis
• Pericardial sac obliterated & adherence of the external aspect of the
parietal layer to surrounding structures
• Cardiac hypertrophy & dilatation
• Constrictive pericarditis
• heart is encased in a dense, fibrous or fibrocalcific scar that limits diastolic
expansion & cardiac output, features that mimic restrictive cardiomyopathy
129. Tumors of heart
• 90% 10 tumor: benign “mesenchymal”: such as myxomas, fibromas,
lipomas, papillary fibroelastomas, rhabdomyomas
• 10% sarcomas: angiosarcoma, etc
• Metastatic tumors 30 times more common than 10 malignancy
• Carcinomas of lung, breast, melanomas, leukemias & lymphoma
•
130. • Primary tumors of heart all are beningn tumor 90%
• There are five primary tumors
• 1. myxoma adult tumor
• 2. fibroma
• 3. lipoma
• 4. papillary fibroelastoma
• 5. Rhabdomyomas in children tumor
131. • The most frequent metastatic tumors involves of heart are
carcinomas lung and breast ,melanomas,leukemia and lymphomas
132. 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 (Trousseau) (NBTE)
• Carcinoid heart disease
• Pheochromocytoma-associated heart disease
• Myeloma-associated amyloidosis
• Effects of Tumor Therapy
• Chemotherapy
• Radiation therapy
134. Left atrial myxoma
• ≈50% 10 tumor of the heart in
adult; benign
• 90% arise in atria (L>R), can
produce a "ball valve" effect by
intermittently occluding the AV
valve orifice
• Embolization of fragments of
tumor may occur
• Dx: echocardiography
138. VHD
Stenosis: failure of a valve to open completely & impeding forward blood
flow
Insufficiency (regurgitation /incompetence): failure of a valve to
close completely & allowing reversed blood flow
Isolated (single valve) or combined ( ≥ one valve)
Pure or mixed (stenosis & incompetence coexist in the same valve)
139. VHD cont.
• Functional regurgitation is the incompetence of a valve 20 to abnormality in one
of its support structures
• Dilation of the Rt. or Lt. Ventricle => pull papillary muscles down & outward = >
preventing proper closure of mitral or tricuspid leaflets
• Dilation of the aortic or pulmonary artery may pull the valve commissures apart
& prevent full closure of the aortic or pulmonary valve cusps
• Blood flow over valvular stenosis or incompetence produces abnormal heart
sounds => Murmurs
141. VHD cont.
• Clinical consequences depend on the valve involved, degree of impairment, how
fast it develops, rate & quality of compensatory mechanisms
• Sudden destruction of the aortic valve cusp in infective endocarditis => massive
regurgitation => rapidly fatal
• Acute mitral regurgitation in myocardial infarction (papillary muscle rupture) =>
cardiogenic shock & may cause death in 48hrs
• Rheumatic mitral stenosis: indolent & well tolerated
142. VHD cont.
• Stenosis => pressure overload
• Insufficiency => volume overload
• Valvular stenosis or insufficiency often produces secondary changes, both
proximal & distal to the affected valve
• Mitral stenosis => left atrium dilates & may harbor thrombus => pulmonary
hypertension => right ventricular hypertrophy; left ventricle unaffected
143. VHD causes
• Congenital or acquired
• AS & MS account for ~2/3rd of all cases of valve disease
• Stenosis is a chronic abnormality of the valve cusp
• Insufficiency
Disease of the valve cusps or damage to supporting structures
Acute or chronic process
• Many potential causes of insufficiency, only few mechanisms produce acquired
stenosis
144. RHD, rheumatic heart disease; IE, infective endocarditis, LV, Left ventricular
MITRAL STENOSIS AORTIC STENOSIS
Post-inflammatory scarring (RHD ) RHD, Senile calcific aortic stenosis
Calcification of congenitally deformed valve
MITRAL REGURGITATION AORTIC REGURGITATION
Abnormalities of Leaflets & Commissures
Post-inflammatory scarring, IE, MVP,
Drugs (e.g., fen-phen)
RHD, IE, Marfan syndrome
Abnormalities of Tensor Apparatus Aortic Disease
Rupture or dysfunction of papillary
muscle, Rupture of chordae tendineae
Degenerative aortic dilation, Syphilitic aortitis
Ankylosing spondylitis, Rheumatoid arthritis
Marfan syndrome
Abnormalities of Left Ventricular Cavity and/or Annulus
LV enlargement (myocarditis, dilated cardiomyopathy), Calcification of mitral ring
Etilogies of Acquired VHD
145. Rheumatic fever (RF)
• is acute immunologically mediated multisystem inflammatory disease that
occurs 2-3wks (10days-6wks) after an episode of Group A β-hemolytic
streptococcal pharyngitis
• Acute rheumatic carditis may progress to chronic rheumatic heart disease (RHD)
with valular abnormalities
• Acute RF commonly appears in children between the ages of 5 & 15, 20% of
first-time attacks occurring in adults
• RHD is common in developing countries
146. Pathogenesis of RF
• Antibodies directed against the M proteins of streptococci cross-react with self
glycoprotein Ags in the heart, joints & other tissues => autoimmune response
(type II hypersensitivity reaction)
• CD4+ T cells specific for streptococcal peptides react with self Ag in the heart &
produce cytokines that activate macrophages (Aschoff bodies)
• The chronic sequelae result from progressive fibrosis due to healing of
inflammatory lesion & the turbulence induced by ongoing valvular deformity
147. Morphology
• Acute RF => focal inflammatory lesions are found in various tissues
• Inflammatory lesions are distinct in the heart & called Aschoff
bodies: lymphocytes (mainly T cells), plump activated macrophages
called Antisckow cells (pathognomonic for RF) & Aschoff giant cells
148. Aschoff bodies
• "Aschoff nodules" seen best in myocardium
• These are centered in interstitium around vessels
150. Acute Rheumatic Fever
• PANCARDITIS (endocarditis, myocarditis, & pericarditis)
• Diffuse inflammation
• Aschoff bodies found in any of three layers of heart
• Pericarditis (fibrinous/serofibrinous) resolve without sequelae
• Endocarditis => fibrinoid necrosis within the cusps or along the tendinous cords
with small vegetations (verrucae) along the lines of closure
• Subendocardial lesions: irregular thickenings called MacCallum plaques, usually
in the left atrium
157. Clinical features
• Up to 6wks after group A streptococci pharyngitis => Acute RF in 3%
• Dx: Jones criteria (major & minor)
• when two of the major criteria, or one major criterion plus two minor criteria
• along with evidence of streptococcal infection i.e., rising Antistreptolysin O titer or DNAase,
158. Jones criteria
Major criteria
1. Migratory polyarthritis of large joints
2. Carditis: tachycardia, arrhythmia, pericardial friction rub, etc
3. Subcutaneous nodules
4. Erythema marginatum of the skin
5. Sydenham chorea: involuntary purposeless uncoordinated jerking
movements affecting primarily the face, feet & hands
Minor criteria
• Fever, arthralgia, raised ESR or C reactive protein,
leukocytosis, rising Antistreptolysin O (ASO) titer or
DNAase, ECG showing heart block, previous RF
160. RHD contd.
• After an initial attack => increased vulnerability to reactivation of
the disease with subsequent pharyngeal infections
• Carditis worsens with each recurrence & damage is cumulative
• Symptomatic chronic rheumatic carditis takes yrs or decades after
acute RF & depend on which cardiac valves involved
161. RHD contd.
• The signs & symptoms of valvular disease depend on which valves
are involved
• Cardiac murmurs, cardiac hypertrophy & dilation
• Heart failure, arrhythmias, thromboembolic complication &
infective endocarditis
• Surgical repair or prosthetic replacement improved the outlook
162. Calcific Aortic Stenosis (AS)
• Age-associated “wear & tear” of either anatomically normal valves or
congenitally bicuspid valves
• Aortic stenosis
• previously normal valves (senile calcific aortic stenosis): presents in the 7th to 9th decades of
life
• stenotic bicuspid valves presents in patients 50 to 70 yrs
• No commissural fusion unlike RHD
• Valve area 0.5-1cm2 (normal 4cm2) => concentric left ventricular (pressure
overload) hypertrophy
• Angina, CHF or syncope => cardiac decompensation & carries a poor prognosis
164. Mitral valve prolapse (MVP)
• One or both mitral leaflets are floppy & prolapse or balloon back into the left
atrium during systole
• Myxomatous degeneration of the mitral valve
• F>>M, unknown basis in most
• Dx: by echocardiogram
• Most asymptomatic
• 3% develop IE, MR, stroke or systemic infarct (embolism of leaflet thrombi), & arrhythmias
168. Hypertension
• Blood pressure ≥ 140/90 mm Hg
• Rises with age, heritable, common in blacks
• 10
• 95%; idiopathic (essential hypertension)
• 20
• 5%
• Renal diseases including renal artery atherosclerosis
• Adrenal diseases (10 aldosteronism, cushing syndrome, pheochromocytoma),
169. Hypertension cont.
• Asymptomatic until late in its course
• Benign or malignant hypertension
• Accelerated or malignant hypertension (5%)
• rapid rising BP that, if untreated, leads to death
• BP>200/120mm Hg (diastolic pressure may exceed 120 mmHg)
• Renal failure; retinal hemorrhage & exudates
171. Systemic (left sided) HHD
• Minimum criteria for diagnosis of systemic HHD
1. Lt. ventricular concentric hypertrophy in absence of other
cardiovascular pathology e.g., aortic valve stenosis, coarctation of
the aorta
2. A history or pathologic evidence of hypertension
172. Morphology of systemic HHD
• Left ventricular hypertrophy intially without dilation
• Left ventricular wall > 2cm, heart weight >500gm
• ↑↑ Left ventricular wall thickness imparts stiffness that impairs diastolic filling
=> left atrial enlargement
• Mic: ↑↑ transverse diameter (>15µm) of myocytes; advanced: variation in cell
size & interstitial fibrosis
173. Normal LV free wall < 1.5
cm
In HHD LV is thickened
(>2 cm)
Systemic HHD
174. Myocardial Cell Hypertrophy
↑ in the transverse diameter of myocytes, variable degrees of cellular &
nuclear enlargement
175. Systemic (left sided) HHD
• Asymptomatic compensated systemic HHD
• ECG or echocardiography show LV enlargement
• Presents with new atrial fibrillation induced by lt. atrial enlargement or CHF
• May develop IHD, stroke, renal damage, heart failure & SCD
• Effective control of hypertension can prevent or lead to regression of cardiac
hypertrophy & its associated risks
176. Pulmonary (right sided) HHD
(Cor Pulmonale)
• Stems from pressure overload of the right ventricle
• Rt. Ventricular hypertrophy, dilation, & potentially failure 20 to pulmonary
hypertension
• Rt. Ventricular enlargement due to congenital heart disease or left ventricular
pathology is excluded
• Pulmonary hypertension is caused by disorders affecting lung structure or
function
• It may be acute (massive pulmonary embolism) or chronic (chronic lung
diseases)
177. Diseases of the Pulmonary
Parenchyma
Chronic obstructive pulmonary disease
Diffuse pulmonary interstitial fibrosis
Pneumoconioses
Cystic fibrosis
Bronchiectasis
Diseases of the Pulmonary Vessels
Recurrent pulmonary thromboembolism
Primary pulmonary hypertension
Extensive pulmonary arteritis (e.g., Wegener
granulomatosis)
Drug-, toxin-, or radiation-induced vascular
obstruction
Extensive pulmonary tumor microembolism
Disorders Affecting Chest Movement
Kyphoscoliosis
Marked obesity (pickwickian syndrome)
Neuromuscular diseases
Disorders Inducing Pulmonary Arterial
Constriction
Metabolic acidosis
Hypoxemia
Chronic altitude sickness
Obstruction to major airways
Idiopathic alveolar hypoventilation
Disorders predisposing to Cor Pulmonale
178. Cor Pulmonale: Morphology
• In acute Cor Pulmonale => rt. Ventricular dilation without hypertrophy
• In chronic Cor Pulmonale => rt. Ventricular hypertrophy (>1cm)
180. Outline: Heart
• Terms
• Heart Failure: Left, Right
• Congenital: shunts (LR or RL) & Obstructive
• Ischemic: Angina, Infarction, Chronic Ischemia, Sudden Death
• Hypertensive: Left sided, Right sided
• Valvular: Rheumatic, AS, MVP, Infective, Non-Infective, Carcinoid, Artificial Valves
• Cardiomyopathy: Dilated, Hypertrophic, Restrictive
• Myocarditis
• Pericardium: Effusions, Pericarditis
• Tumors: Primary, Effects of Other primaries
181. Terms
• Dilatation: enlarged chamber size
• Cardiac hypertrophy: increase in the size of the myocardial fibers
• Cardiomegaly is an increase in cardiac weight or size or both
(hypertrophy &/or dilatation)
186. Cardiac Hypertrophy
• 20 to pressure or volume overload, trophic signal (β-adrenergic
receptor)
• increase heart weight
• Pressure-overload hypertrophy
• Concentric hypertrophy (new sarcomeres added in-parallel)
• increase in wall thickness
• Volume-overload (dilatation) hypertrophy
• Eccentric hypertrophy
• Increase, normal or less than normal in wall thickness
• Ischemia: 2X normal wt. , Hypertension: 3X normal wt.
197. Definition: IE
• Colonization or invasion of the heart valves or the mural
endocardium by a microbe
• But also aorta, aneurysmal sacs, PDA, coarctation , intravascular &
prosthetic devices can be effect
• Formation of bulky friable vegetations (thrombosis & organisms)
• associated with destruction of the underlying cardiac tissues
• Embolization => septic infarcts in brain, kidney, etc
• Most caused by bacteria but also fungi & others
199. Pathogenesis: IE
• Altered valve endothelial surface => platelet-fibrin deposits
• Bacteremia with seeding of NBTE – adherence & growth => further
platelet-fibrin deposition
• Haemodynamic Factors: bacterial colonisation more likely to occur
around lesions with high degrees of turbulence e.g.. small VSD,
valvular stenosis
200.
201. Classification of IE on clinical grounds
• Acute & subacute: severity of the disease & its tempo, virulence of
microorganism & whether underlying cardiac disease is present
• New: native or prosthetic valve endocarditis
202. Acute IE
• Infection of a previously normal heart valve by highly virulent
organism that produces necrotizing, ulcerative, destructive
lesions
• difficult to cure by antibiotics & usually require surgery
• death within days to wks ensues in >50% of patients despite
treatment
203. Subacute IE
• The organisms are of low virulence
• They cause insidious infections of deformed valves that are less
destructive & the vegetation show evidence of healing
• pursue a protracted course of weeks to months
• Cure are often seen after antibiotics
205. Aetiology : IE
• Most originate from the normal flora of the body surface
• Bacteria (gram positive) most common, but rarely fungi (candida), Rickettsiae
(Q fever), & Chlamydiae
Streptococcus viridans 50-60% in previously damaged valves
S. aureus 10-20% in healthy or deformed valves
Prosthetic valve endocarditis by S. epidermidis or Staphylococci
206. Aetiology cont.
• In 10% no organism can be isolated from the blood “culture negative
endocarditis”
• This might be due to prior antibiotics therapy, difficulty in isolating
the organism or deeply embedded organisms within enlarging
vegetation are not released into the blood
207. Portal of entry of the agent in IE
• Factors that lead to Bacteremia
Transient bacteraemia occurs when a heavily colonised mucosa (gut, oral
cavity) or skin surface is traumatised (trivial breaks)
Obvious infection elsewhere
Dental or surgical procedure
Contaminated needle shared by IV drug users
208. Morphology: IE
• Friable, bulky & destructive vegetations containing
fibrin, inflammatory cells & bacteria on the heart valves
or chordae tendineae
• Aortic valve more common than mitral
• Valves of rt. heart (tricuspid) in IV drug abusers
• Single or multiple
• n
214. Morphology: IE
• Infective endocarditis on the mitral valve has spread into the septum all the
way to the tricuspid valve, producing a fistula
215. Microscopy of IE
• friable vegetations of fibrin & platelets (pink) mixed with inflammatory cells &
bacterial colonies (blue)
Bacteria
216. Clinical presentation: IE
• Acute IE => Fever, chills, weakness
• Subacute => absent/slight fever, fatique, loss of weight, flue like
syndrome
• Murmur (may change as vegetation and/or damage to valve
changes)
• Microemboli => subungual hemorrhages, erythematous lesions on
the palms or soles (Janeway lesions), subcutis nodule in the pulp of
the digits (Osler nodes), retinal hemorrhage (Roth spots)
217. Oslers’ nodes
(IC deposition )
Tender, s/c
nodules
Janeway lesions
Nontender
erythematous,
haemorrhagic,
or pustular
lesions often
on palms or
soles.
218. Subungual ("splinter") hemorrhage & numerous petechiae on the skin of
the abdomen are seen in a patient with staphylococcal endocarditis
219. Septic emboli in IE
• Petechial haemorrhages in the
conjunctiva
• Rose spots in retina
220. Diagnosis: IE
• Duke criteria
• Requires either pathologic or clinical criteria
• Pathologic (microorganisms & histologic)
• Clinical (major & minor criteria)
• Echocardiography & blood culture
221. DIAGNOSIS
• 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
222. Complications of IE
• Valvular insufficiency or stenosis with resulting congestive heart
failure
• Myocardial ring abscess
• Suppurative pericarditis
• Septic infarcts & abscesses
• Focal & diffuse glomerulonephritis
223. Prevention of IE
The risk can be lowered in those with predisposing factors before
dental, surgical & other invasive procedure by prophylaxis with
antibiotics
225. NBTE
• Deposition of small sterile thrombi on the closure lines of valve
cusps or leaflets
• Often encountered in debilitated patients (cancer or sepsis) =>
marantic endocarditis
• Vegetations (1-5mm) are sterile, loosely attached, nondestructive &
no inflammatory reaction => may eventually organize leaving
delicate strands of fibrous tissue
• Local effect on the valves is unimportant
• Emboli => infarcts in brain, heart, etc
226. Pathogenesis: NBTE
Hypercoagulable state such as cancer e.g. mucinous
adenocarcinomas => procoagulant effect of tumor derived mucin or
tissue factor
May be seen with hyperestrogenic state, extensive burns, or
endocardial trauma from indwelling catheters (Swan-Ganz catheter-
related pulmonary valve nonbacterial endocarditis)
227. NBTE
• The valve is seen on the left, and a bland vegetation is seen on the right
231. Comparison of four major forms of vegetative
endocarditis
Vegetations: 1) rheumatic = small, at chordae tendinae junction,
2) infectious = big (>5 mm), 3) lupus (Libman-Saks) = BOTH sides
4) NBTE = non-bacterial thrombotic endocarditis (<5 mm)
232. Carcinoid heart disease
• Seen in ½ of patients with carcinoid syndrome
• Involves endocardium and valves of the right heart => tricuspid &
pulmonary insufficiency
• Plaque like endocardial fibrous intimal thickening on RV, Tricuspid
valve, Pulmonic valve (all RIGHT side)
• Serotonin, kallikrein, bradykinin, histamine, etc appear to induce
the cardiac lesions
