Heart and Cardiac Pathology

NORMAL

Valve normal histology

§    Endothelium

§    Elastic fiber-rich subendothelial stroma

§    Lamina fibroma (thick collagenous tissue)=main bulk

§    Elastic fiber-rich subendothelial stroma

§    Endothelium

Changes in the Aging Heart

 

 

 

HEART FAILURE

CARDIAC HYPERTROPHY

§    Path effects of pressure vs. volume overload

§    P → concentric HP

§    V → concentric HP and dilatation

§    Compensatory mechanisms of CHF

Ø   myocyte hypertrophy

Ø   ventricular dilatation

Ø   ↑ECV

Ø   tachycardia

LEFT-SIDED HEART FAILURE

§    RF

Ø   IHD

Ø   HTN

Ø   AV and MV dz

Ø   Myocardial dz

§    Lungs

Ø   heavy wet lungs

Ø   interstitial transudate, edema alveolar septae, edema, heart failure mφ

Ø   dyspnea, orthopnea, PND

§    Kidneys

Ø   ↑retention of water via RAS

Ø   Pre-renal azotemia (↓excretion of nitro.)à ATN

§    Brain

Ø   hypoxic encephalopathy

RIGHT-SIDED HEART FAILURE

§    RF

Ø   Left-sided heart failure

§    #1 cause

Ø   Pulmonary HTN

§    Cor pulmonale

Ø   Valvular disease (TV, PV)

Ø   Interstitial lung disease

§    Liver/spleen

Ø   hepatomegaly, splenomegaly, ascites

Ø   congestion of sinusoids, centrolobular necrosis

Ø   cardiac sclerosis (centrolobular)

§    Kidneys

Ø   congestion

§    Brain

Ø   Venous congestion

Ø   Lungs/pericardium

Ø   pleural effusions/pericardial effusions

Ø   SQ

Ø   Edema

 

Name 5 types of heart disease:

§    Ischemic

§    Valvular

§    Cardiomyopathies

§    Myocarditis

§    Congenital

ISCHEMIC HEART DISEASE

4 clinical manifestations of ischemic heart disease?

§    MI

§    Angina

§    chronic IHD with CHF

§    sudden death

Pathogenesis (4)

§    Fixed coronary obstruction

§    Acute plaque change

§    Vasoconstriction

§    Coronary thrombus

Acute plaque change can occur in (3) ways

§    Rupture an existing plaque

§    Fissure

§    Ulceration of existing plaque

Pathophysiologic mechanisms

§    Stable angina

Ø   Increase in oxygen demand which is greater than the oxygen carrying capacity of the stenosed coronary vesselà >75% stenosis

§    Unstable angina

Ø   Acute plaque change causing partial occlusion  +/- vasoconstriction

§    MI

Ø   Acute plaque change causing complete obstruction & causing a fatal arrhythmia

MYOCARDIAL INFARCTION

Non-CAD causes

§    Pheochromocytoma-induced HTN

§    Vasopressors

Drugs (amphetamines, Ephedra, cocaine)

Clinical

§    Distribution of transmural vs. subendocardial…which is assoc.

Ø   with diffuse coronary atherosclerosis

Ø   with acute plaque change, followed by lysis of thrombosis

§    risk factors (5)

Sequence of events in coronary artery

§    Acute plaque change

§    Exposed collagen/plaque adhere to PLT→ TxA2 and vasoconstriction

§    Extrinsic pathway activated

§    Occlusion of vessel by thrombus

Sequence of events in ischemic coronary myocytes

§    (seconds / <2min / 10 min / 40min / 20-40min / >1hr)

§    sec: onset of ATP depletion

§    <2m: loss of contractility

§    10m: 50% ATP left

§    40m: 10% ATP left

§    20-40m: irreversible injury

§    >1hr: microvascular injury

Histo and cause of myocytolysis:

§    subendothelial vacuolation of myocytes secondary to chronic ischemia

Histology in reperfusion injury

§    contraction band necrosis

Complications of MI:

§    pericardium

Ø   fibrinous pericarditis

§    myocardium

Ø   free wall rupture

Ø   aneurysm

Ø   contractile dysfunction

Ø   infarct extension and expansion

Ø   papillary muscle dysfunction

Ø   CHF

§    Endocardium

Ø   mural thrombus

§    conduction system

Ø   arrhythmias

Changes from chronic MI

§    dilation and hypertrophy

§    myocyte hypertrophy, myocytolysis, fibrosis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Myocardial Infarction

 

HYPERTENSIVE HEART DISEASE

Systemic hypertensive heart disease

Pulmonary hypertensive heart disease

Disorders Predisposing to Cor Pulmonale

 

VALVULAR HEART DISEASE

§    Most frequent lesions

Ø   Aortic stenosis

§    2% population

§    Ca++ normal, bicuspid, unicuspid

Ø   Aortic insufficiency

§    Dilated ascending aorta

• Age
• HTN

Ø   Mitral stenosis

§    RHD

Ø   Mitral insufficiency

§    Myxomatous degeneration

§    Acquired or congenital

Ø   Acquired stenoses of aortic and mitral valves account for 2/3 of ALL cases of valve disease

§    Stenosis

Ø   Failure to open completely

Ø   Impedes outflow

Ø   P overload

§    Insufficiency/regurgitation

Ø   Failure to close completely

Ø   Allows reverse blood flow

Ø   V overload

Degeneration of valves due to Ca++

Calcific aortic stenosis

§    Age at px related to valve:

Ø   Normal → 7^th-9^th decades

Ø   Bicuspid → 5^th-7^th decades

Ø   Unicuspid → early to teenage yrs.

§    Gross

Ø   Calcified masses

§    Micro

Ø

Ca++ of congenital bicuspid AV

§    1% of population

§

Mitral annular calcification

§    old women

§    myxomatous mitral valve

§    stony hard nodule behind leaflet

§    Complications

Ø   MV infective endocarditis

Ø   Arrhythmias

Ø   CVA

Mitral valve prolapse

§    myxomatous, hooding, ballooning

§    attenuation of fibrosa layer, myxomatous material

§    Secondary changes: MV thrombus & calcifications, LA and LV fibrosis

§    Complications: IE, stroke, MV insufficiency, sudden death

RHEUMATIC HEART DISEASE

§    Infectious agent

Ø   Beta hemolytic group A Streptococcus

§    Jones criteria for diagnosis

Ø   Evidence of group A strep infection AND

§    Antibodies to bacterial enzymes

• Streptolysin O
• DNase B

Ø   2 major OR

Ø   1 major + 2 minor

§    Five major manifestations of rheumatic fever

Ø   Migratory polyarthritis (predominantly large joints)

Ø   Carditis and valvulitis (pancarditis)

Ø   Central nervous system involvement (Sydenham chorea)

Ø   Erythema marginatum

§    pink to faintly red, non-pruritic rash

§    trunk +/- limbs, but not face

Ø   Subcutaneous nodules

§    near tendons or over a bony surface or prominence

§    Four minor manifestations

Ø   Arthralgia

Ø   Fever

Ø   Elevated acute phase reactants  (ESR, CRP)

Ø   Prolonged PR interval

§    Acute RHD

Ø   Myocardium and pericardium (3): myocarditis, Aschoff bodies, pericarditis

Ø   Valve region (2)à atrium: fibrinoid necrosis and fibrosis of vegetations, MacCallum plaques

§    Chronic RHD

Ø   MV (leaflets cords): fusion of commissures, thickening of leaflets, shortening, fusion and thickening of cords.

Ø   Fish mouth stenoses

Ø   Fibrosis and bv prol.

Which valves (2) which more common?

§    MV alone

§    MV+ AV

§    Pathogenesis

Ø   autoAb directed at M proteins cross react with tissue glycopr

§    Risks

Ø   IE

Ø   stroke (from emboli)

Ø   arrhythmia (a fib)

Ø   MV insufficiency (CHF, LVH)

ENDOCARDITIS

Infective endocarditis

§    Duke criteria

Ø   Pathologic

§    Demonstration of organisms by histology

Ø   Clinical

§    Predisposing factors

§    Physical findings

§    Blood cultures

§    EKG

§    Lab findings

§    Major Diagnostic Criteria

Ø   Positive blood culture for typical organisms from 2 separate blood cultures or 2 positive cultures from samples drawn > 12 hours apart

Ø   Specific EKG findings

§    Minor Diagnostic Criteria

Ø   Predisposing heart condition or IVDU

Ø   T > 38° C

Ø   Vascular: arterial emboli, pulmonary infarcts, mycotic aneurysms, intracranial bleed, conjunctival hemorrhages, Janeway lesions

Ø   Immunologic: glomerulonephritis, Osler nodes, Roth spots, RF

Ø   Microbiology: positive blood culture not meeting major criteria

Ø   EKG findings not meeting major criteria

§    Murmurs 90%

§    Janeway lesions

Ø   Small non-tender, erythematous/hemorrhagic lesions on palms and soles

Ø   Secondary to septic emboli

§    Osler nodes

Ø   Small, tender subcutaneous nodules in pulp of digit

Ø   Secondary to vasculitis

§    Roth spots

Ø   Oval retinal hemorrhage with central pale spot

Ø   Secondary to vasculitis

§    Acute

Ø   Highly virulent organism

Ø   Normal valves

Ø   Stormy onset: rapidly developing fever

Ø   Elderly: flu-like sx only

Ø   Necrotizing, ulcerative destructive lesions

Ø   Not curable by Abx, requires sx

Ø   Death within days to weeks

§    Subacute

Ø   Lower virulence organisms

Ø   Deformed valves

Ø   Cured by Abx

§    RFs

Ø   RHD

Ø   MVP

Ø   Prosthetic valve

Ø   Degenerative calcific valve

Ø   Bicuspid aortic valve

Ø   Un-repaired or repaired congential defects

Ø   dental

Ø   IV

Ø   Sepsis

Ø   Infection

Ø   DM

Ø   immunosuppression

§    Organisms

Ø   Staphylococcus aureus 30%

§    Virulent skin commensal

§    Normal or deformed valves

§    IVDU

Ø   Streptococcus viridans 15%

§    Deformed valves

§    Oral commensal

Ø   Staphylococcus epidermidis 10%

§    Prosthetic valves

Ø   Fungi 2%

Ø   HACEK 2%

§    Fastidious gram-negative bacilli

§    Oral commensals

• Haemophilus aphrophilus
• Actinobacillus actinomycetemcomitans
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella kingae

§    Gross

Ø   Friable, bulky, destructive

Ø   Aortic and mitral valves most commonly affected

Ø   Right heart involved with IVDU

§    Micro

Ø   Fibrin

Ø   Inflammatory cells

Ø   Bacteria/organisms

Ø   Ring abscess

§    Complications

Ø   Abscess

Ø   Emboli (septic infarcts, mycotic aneurysms), CHF, pericarditis, emboli, kidney: focal/diffuse GN

Nonbacterial thromboendocarditis (NBTE)

§    AKA marantic endocarditis

§    Small, sterile thrombi

§    Gross

Ø   1-5 mm

Ø   Line of closure

Ø   Leaflets or cusps

§    Micro

Ø   Bland adherent thrombi

Ø   Non-destructive

Ø   No inflammation

§    Clinical consequences

Ø   Source of systemic emboli

§    Brain

§    Heart

§    Other

§    RF

Ø   DVT

Ø   PE

Ø   DIC

Ø   Mucinous adenocarcinomas

§    Pancreas (Trousseau syndrome of migratory thrombophlebitis)

Ø   Burns

Ø   PICC line

Endocarditis of SLE (Libman-Sacks endocarditis)

§    Mitral and tricuspid valvulitis

§    Gross

Ø   1-4 mm

Ø   Multiple

Ø   Undersurface, mural endocardium, chordae tendinea

Ø   Pink

Ø   Warty/verrucous appearance

§    Micro

Ø   Finely granular eosinophilic fibrinous material

Ø   Hematoxylin bodies

Ø   Homogenous nuclear remnants

§    Anti-nuclear Ab

§    Clinical consequences

Ø   Fibrosed, deformed valves

Ø   Require sx

CARCINOID HEART DISEASE

CARCINOID SYNDROME

§    Caused by liver mets, ovary and lung primaries (all bypass portal venous system)

§    “Biologically active substances” released→ serotonin, tachykinin, bradykinin, histamine, prostaglandins

Clinical

§    Flushing, hypertension, sweating, palpitations

§    Gross

Ø   Fibrosclerosis involving only RV, RA, TV and PVà therefore only right heart

Ø   “carcinoid heart disease”, tumour itself

Ø   Valves contain serotonin receptors which activate MFB in valves

§    Micro of plaques

Ø   SM and MFB

Ø   Mucopolysaccharide matrix

Ø   Plaques do not destroy underlying valve but rather deposit on it

§    Why right-side of heart?

Ø   5-HT and bradykinin are degraded by monoamine oxidases in the pulmonary circulation

§    Why only liver mets?

Ø   bioactive substances released into the portal system and therefore not degraded by the liver

Complications of Artificial Valves

 

CARDIOMYOPATHIES

 

 

 

 

 

 

 

 

Hypertrophic cardiomyopathy = blue

Hypertrophic and dilate cardiomyopathy = green

Dilated cardiomyopathy = red

 

Cardiomyopathy

§    Heart disease resulting from an abnormality in the myocardium

§    Consequences

Ø   Diastolic or systolic dysfunction

Ø   Abnormal wall thickness and/or chamber size

Ø   Mechanical and/or electrical dysfunction

§    Primary

Ø   Confined to heart

§    Secondary

Ø   Part of systemic illness

 

 

Dilated CM: all cardiac chambers dilated + hypertrophy

Hypertrophic CM: LVH + dilated LA

Restrictive CM: dilated atria
DILATED CARDIOMYOPATHY

§    Hypertrophy + 4 chamber dilatation

§    Contractile/systolic dysfunction

§    Genetic

Ø   50%

Ø   AD inheritance most common

Ø   Cytoskeletal or mitochondrial (Mt) proteins

Ø   Mt defects frequently cause dilated cardiomyopathy in children

Ø   X-linked

§    Clinical px in teens or early 20s

§    Rapidly progressive

§    Dystrophin, a cytoskeletal protein that scaffolds internal cytoskeleton to ECM, also mutated in skeletal myopathies (Duchenne, Becker)

§    Myocarditis

Ø   Coxsackievirus B

Ø   Other enteroviruses

§    Alcohol

Ø   Alcohol +/- metabolites (esp. acetaldehyde) direct toxic effect on myocardium

Ø   No distinguishing morphologic features from other DCMs

Ø   Thiamine deficiency leads to beriberi heart disease

§    Other toxins

Ø   Chemotherapeutic agents

§    Doxorubicin (Adriamycin)

Ø   Cobalt

§    Peripartum

Ø   Late in pregnancy or weeks to months postpartum

Ø   Pregnancy-associated HTN

Ø   Volume overload

Ø   Nutritional deficiency

Ø   Other metabolic derangements

Ø   Uncharacterized immunological rxn

Ø   ? Anti-angiogenic cleavage product of prolactin (rises late in pregnancy)

Ø   Blocking prolactin secretion by bromocriptine in mouse models prevents peripartum cardiomyopathy

§    Gross

Ø   Heavy (weighing 2-3X normal)

Ø   Dilated chambers (x4)

Ø   Enlarged

Ø   Flabby

Ø   Mural thrombi

Ø   No evidence of

§    Valvular disease

§    CAD

§    Micro

Ø   Nonspecific

Ø   Hypertrophied myocytes

Ø   Enlarged, attenuated, stretched, or irregular nuclei

Ø   Variable interstitial and endocardial fibrosis

Ø   Small subendocardial scars

§    Healed areas of ischemic necrosis

ARVC

§    Arrhythmogenic right ventricular cardiomyopathy

§    Triangle of dysplasia

Ø   Anterior RV wall

§    Micro triad

Ø   Severe fatty infiltration from epicardium inwards with preservation of inner trabeculae

Ø   Fibrosis

Ø   Inflammation

§    Plakoglobin mutations

Ø   Link adhesion molecules at intercalated disc to cytoskeleton

§    Disease can also affect LV

HYPERTROPHIC CARDIOMYOPATHY

§    Leading cause of unexplained LVH

§    Sarcomeric protein mutations

Ø   beta myosin heavy chain (most common)

Ø   TnT

Ø   α-tropomyosin

Ø   Myosin-binding protein C

§    Thick-walled, heavy, hyper-contracting heart in contrast to flabby, hypo-contracting DCM heart

§    Diastolic dysfunction d/t ↓chamber size and compliance

§    Distinguish from deposition (amyloidosis, Fabry’s disease) and HTN heart disease

§    Gross

Ø   Massive myocardial hypertrophy, without ventricular dilation

Ø   Disproportionate thickening of ventricular septum as compared with free wall of LV (ratio greater than 1:3) most prominent in subaortic region

Ø   Asymmetric septal hypertrophy

Ø   Ventricular cavity loses its round-to-ovoid shape and has a “banana-like” configuration

Ø   +/- Endocardial thickening or mural plaque in LV outflow tract

Ø   +/- Thickened anterior mitral leaflet (from contact with septum)

§    Micro

Ø   Myocyte hypertrophy

§    Transverse myocyte diameters >40 μm (normal 15 μm)

Ø   Myocyte disarray

Ø   Interstitial and replacement fibrosis

§    Clinical

Ø   AF

Ø   Mural thrombus formation → embolization, stroke

Ø   Intractable CHF

Ø   Ventricular arrhythmias

Ø   Sudden unexplained death

§    Common cause in young athletes

RESTRICTIVE CARDIOMYOPATHY

Define

Causes (5)

§    Amyloidosis

§    Hemochromatosis

§    Sarcoidosis

§    Radiation fibrosis

§    Tumour

Gross

§    Normal or hypertrophy + biatrial dilatation

Micro

§    Fibrosis

Diagnosis

§    Endomyocardial biopsy

 

 

MYOCARDITIS

 

 

§    Infectious

Ø   CoxAB,

Ø   Lymeà Borrelia burgdorferi

Ø   T. cruzi

§    Non-infectious

Ø   allergic hypersensitivity

Ø   doxorubicin

Ø   sarcoidosis, lupus, hemochromatosis

Ø   cocaine (catecholamine effect)

Ø   focal patchy lf,  so endomyocardial bx often –ve

Ø   hypersensitivity myocarditis (↑eosinophils)

Ø   giant cell myocarditis

OTHER CARDIAC DISEASES

§    Cardiac Amyloidosis 1^o vs. 2^o

§    Fe++ overload

§    Hyperthyroidism

§    Hypothyroidism

§    Gross: flabby and dilated

§    Micro: “Myxedema heart” (myocyte swelling w/ interstitial mucopolysaccharide deposition)

PERICARDITIS

§    Types of acute pericarditis (5)

Ø   Serous

Ø   Fibrinous and Serofibrinous

Ø   Purulent

Ø   Hemorrhagic

Ø   Caseous

§    Serous

Ø   non-infectious (lupus, RA)

Ø   PMN +l φ

§    Fibrinous and serofibrinous

Ø   acute MI

Ø   post MI (Dressler synd)

Ø   radiation

Ø   RF

Ø   SLE

Ø   trauma

Ø   fine granular roughening

Ø   friction rub

§    Purulent or suppurative

Ø   direct (pneumonia), blood, lymph, cardiac sx (direct)

Ø   creamy pus with red granular roughening

§    Hemorrhagic pericarditis

Ø   cardiac sx

Ø   tumour

§    Caseous pericarditis

Ø   TB

PRIMARY CARDIAC NEOPLASMS

Myxoma

§    atria

§    sessile, pedunculated masses, damage to leaflets (wrecking ball effect)

§    stellate cells in a mucopolysaccharide matrix

§    w/ endothelial surface

§    Carney synd (AD

Lipoma

Papillary fibroelastoma

§    hairlike projections on valves that may embolize

Rhabdomyoma

§    childhood

§    in ventricles, protrude into the chamber

§    TSC

 

 

 

 

 

 

 

 

 

Effects of Noncardiac Neoplasms

 

CONGENITAL HEART DISEASE

§    Structural anomalies in congenital heart disease fall primarily into three major categories:

Ø   Malformations causing a left-to-right shunt

Ø   Malformations causing a right-to-left shunt

Ø   Malformations causing an obstruction

§    4 left-to-right shunt/non-cyanotic heart disease

Ø   ASD

Ø   VSD

Ø   ASVD

Ø   PDA

§    5 types of cyanotic heart disease

Ø   Tetralogy of Fallot

Ø   Transposition of Great Arteries

Ø   Truncus Arteriosus

Ø   Tricuspid atresia

Ø   Total Anomalous Pulmonary Venous Connection (TAPVC)

Ø   Clinical SSx

§    Cyanosis

§    Clubbing (hypertrophic osteoarthropathy)

§    Polycythemia

§    Paradoxical emboli

 

 

 

 

LEFT TO RIGHT SHUNTS

 

 

ASD

§    Asymptomatic until adulthood (30 yo)

§    3 major types

Ø   Secundum

§    90%

§    deficient or fenestrated oval fossa

§    near center of atrial septum

§    not associated with other anomalies

§    any size

§    single or multiple

Ø   Primum

§    5%

§    adjacent to AV valves

Ø   Sinus venosus

§    5%

§    near entrance of SVC

§    +/- anomalous pulmonary venous return to right atrium

 

 

Patent Foramen Ovale

§    Open flap in atrial septum at fossa ovalis

§    Functional R-to-L shunt in fetus

Ø   O₂-rich blood bypasses lungs

§    Forced shut at birth with ↑P in L heart

§    80% permanent closure

§    20% unsealed flap

§    Can re-open with ↑R heart P

Ø   Sustained pulmonary HTN

Ø   Transient with Valsalva maneuver (bowel movement, coughing, or sneezing)

§    Paradoxical embolism

VSD

§    Most common congenital cardiac anomaly

§    20-30% isolated

§    Remainder assoc. with cardiac anomalies

§    Types

Ø   Membranous

§    90%

§    Large

Ø   Muscular/infundibular

§    Below pulmonary valve, within muscular septum

§    50% of small VSDs close spontaneously

§    Rarely multiple, “swiss cheese”

§    Consequences if large

Ø   RVH

Ø   Pulmonary HTN

§    Ultimately shunt reversal, cyanosis, death

• Eisenmenger syndrome

PDA

§    Functional R-to-L shunt in fetus

Ø   O₂-rich blood bypasses lungs

§    Fails to spontaneously close at birth

Ø   Continuous harsh murmur, “machinery-like”

Ø   Asymptomatic

§    90% isolated

Ø   Should be closed ASAP

§    10% + malformations that obstruct pulmonary or systemic outflow tracts

Ø   VSD

Ø   Coarctation of aorta

Ø   Pulmonary valve stenosis

Ø   Aortic valve stenosis

Ø   Preservation of patency essential

§    Prostaglandin E

 

AVSD

§    Endocardial cushions of AV canal fail to fuse

§    Partial

§    Complete

Ø   30% Down syndrome

RIGHT TO LEFT SHUNTS

Tetralogy of Fallot

§    Anterosuperior displacement of infundibular septum

§    4 cardinal features

Ø   Large VSD

Ø   Aorta overriding left and right ventricles

Ø   Right ventricular outflow tract obstruction

§    Subpulmonic valve/infundibular stenosis

§    Determines clinical consequences

Ø   RVH

§    Boot-shaped heart d/t RVH esp. at apex

§    85% sporadic

Ø   NKX2.5

Ø   TBX1

§    15% assoc. syndromes

Ø   Down

Ø   Alagille (JAGGED1)

Ø   DiGeorge

Ø   Velocardiofacial

Transposition of great arteries

§    Abnormal truncal and aortopulmonary septa

§    Discordant ventriculoarterial connections

Ø   Aorta arises from RV (anterior and to right of PA)

Ø   PA arises from LV

§    Concordant AV connections

Ø   RA joins RV

Ø   LA joins LV

§    Separate systemic and pulmonary circulations

§    Incompatible with life unless shunt present for mixing of blood

Ø   VSD: stable shunt

Ø   Patent foramen ovale: unstable shunt

Ø   Patent ductus arteriosus: unstable shunt

§    RVH and LV atrophy

 

Persistent truncus arteriosus

§    Failure of truncus arteriosus to separate into aorta and pulmonary artery

§    Single great artery receives blood from both ventricles

Ø   Systemic, pulmonary, coronary circulations

§    + VSD

Tricuspid atresia

§    Unequal division of AV canal

§    Complete occlusion of tricuspid valve orifice

§    Large MV

§    Hypoplastic RV

§    R-to-L shunt required to maintain circulation

Ø   ASD

Ø   Patent foramen ovale

Ø   VSD

OBSTRUCTIVE CONGENITAL ANOMALIES

Coarctation of aorta

Ø  Upper extremities HTN

Ø  Lower extremities weak pulses, hypotension, and arterial insufficiency

§    Claudication, coldness

Ø  Collateral circulation between pre-coarctation arterial branches and post-coarctation arteries through enlarged intercostal and internal mammary arteries

Ø  Visible erosions/notching of rib under-surfaces

Ø  Infantile form

§    Tubular hypoplasia of aortic arch proximal to a patent ductus arteriosus

§    Symptomatic in early childhood

Ø  Adult form

§    Discrete ridge-like infolding of aorta

§    Opposite to closed ductus arteriosus (ligamentum arteriosum)

§    Distal to arch vessels

Ø  50% bicuspid aortic valve

 

Pulmonary stenosis or atresia

Aortic stenosis or atresia

§    80% isolated

§    Less severe degrees of congenital aortic stenosis may be compatible with long survival

§    Valvular

Ø   Hypoplastic (small), dysplastic (thickened, nodular), or abnormal in number (acommissural or unicommissural) cusps

Ø   Hypoplastic LV and ascending aorta

Ø   Porcelain-like left ventricular endocardial fibroelastosis (if severe)

§    Subaortic stenosis

Ø   Thickened ring (discrete type) or collar (tunnel type) of dense endocardial fibrous tissue below level of cusps

§    Supravalvular aortic stenosis

Ø   Inherited form of aortic dysplasia

§    Elastin gene deleted

Ø   Ascending aorta greatly thickened

§    Luminal constriction

Ø   Other features: hypercalcemia, cognitive abnormalities, and hallmark facial anomalies

 

COMPLICATIONS OF VALVULAR DISEASE INCLUDING MVP

§    arrhythmias à leading to sudden death

§    thromboemboli à leading to ischemia or stroke in distal organs

§    valvular incompetence

§    infective endocarditis

INDICATIONS FOR ENDOMYOCARDIAL BIOPSY

§    Cardiomyopathies in general

Ø   To differentiate constrictive vs restrictive

Ø   Myocarditis[1]

Ø   Infiltrative lesions[2]

§    Arrhythmias

§    Drug toxicities[3]

§    Neoplasias

§    Transplant rejection surveillance (no1)

§    Metabolic disorders[4]

§

ADJUNCTIVE STUDIES FOR ENDOMYOCARDIAL BIOPSY

MYOCYTE DISARRAY

§    Fabry?

§    Hypertrophic CMP

§    Some congenital heart disease

CAUSES OF NON-ATHEROSCLEROTIC CAD

§    Dissection[5]

§    Vasculitis

§    Congenital coronary artery anomalies

§    Coronary fistula

§    High take-off position of coronary ostia

§    Infectious

§    Kawasaki

§    Metabolic disorders

§    Metastasis

§    Drugs (cocaine)

§    Myocardial bridges

§    Aneurysm[6]

§    Emboli

§    Spasm (Prinzmetal)

3 MOST COMMON CAUSES OF ACUTE CORONARY INTRALUMINAL OBSTRUCTION

§    Atheromatous thin cap plaques

§    Plaque erosion

§    Calcified nodule[7]

CAUSES OF CALCIFICATION IN VALVES

§    Age-related degenerative changes

§    Metastatic calcification (hyperPTH)

CAUSES OF SUDDEN CARDIAC DEATH

§    Unexpected death from cardiac cause in individual without symptomatic heart disease or early after symptom onset (usually within 1 hour)

§    Most SCD not associated with acute MI

§    Usually d/t lethal arrhythmia on a background of ischemic heart disease

Ø   Asystole

Ø   Ventricular fibrillation

§    Acute myocardial ischemia is the most common trigger for fatal arrhythmias

§    Fatal arrhythmias usually result from acute ischemia-induced electrical instability of myocardium that is distant from the conduction system

§    Scars of previous infarcts and subendocardial myocyte vacuolization indicative of severe chronic ischemia are common in such patients

§    Arrhythmogenic foci are often located adjacent to scars left by old MIs

§    80-90% with critical stenosis (>75%) involving one or more of three coronary artery vessels

§    10-20% are of nonatherosclerotic origin

§    Non-atherosclerotic conditions associated with SCD:

Ø   Congenital structural or coronary arterial abnormalities

Ø   Aortic valve stenosis

Ø   Mitral valve prolapse

Ø   Myocarditis

Ø   Dilated or hypertrophic cardiomyopathy

Ø   Pulmonary hypertension

Ø   Hereditary or acquired cardiac arrhythmias

Ø   Cardiac hypertrophy of any cause (e.g., hypertension)

Ø   Systemic metabolic and hemodynamic alterations

Ø   Catecholamines

Ø   Drugs

§    Cocaine

§    Methamphetamine

§    Heritable conditions

Ø   Intervention in surviving family members

Ø   Some associated with recognizable anatomic abnormalities (e.g., congenital anomalies, hypertrophic cardiomyopathy, mitral valve prolapse)

Ø   Some have no gross abnormalities

Ø   Channelopathies

Ø   Long QT syndrome

§    KCNQ1 gene (most frequently mutated)

Ø   Brugada syndrome

Ø   Short QT syndrome

Ø   Catecholaminergic polymorphic ventricular tachycardia

Ø   Wolff-Parkinson-White syndrome

Ø   Congenital sick sinus syndrome

§    Implantation of a pacemaker or an automatic cardioverter defibrillator, which senses and electrically counteracts an episode of ventricular fibrillation.