Lec 2, Congenital Heart Diseases

8/15/2019 Lec 2, Congenital Heart Diseases

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Congenital Heart Diseases

Special Pathology



Congenital heart diseases

• abnormalities of the heart or great vessels that are

present at birth – faulty embryogenesis during gestational weeks 3 through

– ma!or cardiovascular structures develop"

• Congenital malformations of the heart encompass a

broad spectrum of defects# – severe anomalies that cause death in the perinatal period#

– mild lesions that produce only minimal symptoms# even in adultlife"

• $enerally accepted incidence is appro%imately &' of live

births – higher in premature infants and in stillborns"

• (ost common type of heart disease among children"



• Patients surviving with congenital heart disease

is increasing rapidly – )ecause of clinical advances – by *+*+ there will be an estimated ,-+#+++ adults

with congenital heart disease"

• Surgery can correct the hemodynamicabnormalities – repaired heart may still not be completely normal – .lthough adaptive initially# such changes can elicit

late/onset arrhythmias# ischemia# or myocardial

dysfunction# sometimes many years after surgery• (yocardial hypertrophy and a cardiacremodeling brought about by the congenitaldefect may be irreversible"





• Cardiac morphogenesis – involves multiple genes

– tightly regulated to ensure an effective embryoniccirculation"

• 4ey steps involve specifying cardiac cell fate# morphogenesisand looping of the heart tube# segmentation and growth of thecardiac chambers# cardiac valve formation# and connection ofthe great vessels to the heart"

– 2he molecular pathways controlling such cardiacdevelopment

• provide a foundation for understanding the basis of somecongenital heart defects"

– Several congenital heart diseases are associated with

mutations in transcription factors"• (utations of the 2)5- transcription factor cause the atrial and

ventricular septal defects seen in Holt/6ram syndrome"• (utations in the transcription factor 745*"- are associated

with isolated atrial septal defects 1.SDs"



• Since different cardiac structures can share the samedevelopmental pathways# – dissimilar lesions may be related to a common genetic defect

• 2he unifying feature of many outflow tract defects is theabnormal development of neural crest/derived cells# – whose migration into the embryonic heart is re8uired for outflow tract

formation"

• 9n particular# genes located on chromosome ** have ama!or role in forming the conotruncus# the branchial arches#and the human face: – 7ow known that deletions of chromosome **8&&"* underlie &-' to

-+' of outflow tract abnormalities"

– can also cause developmental anomalies of the fourth branchial archand derivatives of the third and fourth pharyngeal pouches

• leading to thymic and parathyroid hypoplasia

• resultant immune deficiency 1Di $eorge syndrome and hypocalcemia"



• 2welve disorders account for -' of

congenital heart disease: their fre8uenciesare shown in 2able"

• Congenital heart diseases can be

subdivided into three ma!or groups; – (alformations causing a left-to-right shunt

– (alformations causing a right-to-left shunt

1cyanotic congenital heart diseases – (alformations causing obstruction



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 77

!oarctation of t"e aorta 4#2

Atrio$entricular septal defect 3#6 4

Aortic stenosis 388 4

Transposition of t"e great arteries 388 4

Truncus arteriosus 136 1

Total anomalous pulmonary $enous connection 120 1

Tricuspid atresia 118 1

T%TA& #77



• Shunt – abnormal communication between chambers or blood vessels" – Depending on pressure relationships# shunts permit the flow of blood

from the left heart to the right heart 1or vice versa"

– Right-to-left shunt • dusky blueness of the skin (cyanosis) results• pulmonary circulation is bypassed• poorly o%ygenated blood enters the systemic circulation"

– Left-to-right shunts • increase pulmonary blood flow

• not associated 1at least initially with cyanosis• e%pose the low/pressure# low/resistance pulmonary circulation to

increased pressure and volume# resulting in right ventricular hypertrophyand/eventually/right/sided failure"

– obstructive congenital heart disease • Some developmental anomalies obstruct vascular flow by narrowing the

chambers# valves# or ma!or blood vessels:

• . complete obstruction is called an atresia. • 9n some disorders 1e"g"# tetralogy of <allot# an obstruction 1pulmonary

stenosis is associated with a shunt 1right/to/left through a ventricularseptal defect =>SD?"



• @eft/to/right shunts: – most common type of congenital cardiac malformation 1<ig"

– atrial and ventricular septal defects# and patent ductus arteriosus.

• .trial septal defects are typically associated with increased pulmonaryblood volumes

• ventricular septal defects and patent ductus arteriosus result in bothincreased pulmonary blood flow and pressure"

– 2hese malformations can be asymptomatic or can cause fulminantCH< at birth"

– yanosis is not an early feature of these defects# but it can occurlate#

• Eisenmenger syndrome. – after prolonged left/to/right shunting has produced pulmonary hypertension

sufficient to yield right/sided pressures that e%ceed those on the left and thusresult in a reversal of blood flow through the shunt

– Aationale for early intervention# either surgical or nonsurgical• 6nce significant pulmonary hypertension develops#

• structural defects of congenital heart disease are considered irreversible





• .SDs – normal atrial septation 1<ig"

• begins as an ingrowth of the septum primum from the dorsal wall of thecommon atrial chamber toward the developing endocardial cushion!

– a gap# termed the ostium primum, initially separates the two"• Continued growth and fusion of the septum with the endocardial cushion

ultimately obliterates the ostium primum: however# – a second opening# ostium secundum, now appears in the central area of the

primary septum – allowing continued flow of o%ygenated blood from the right to left atria# essential

for fetal life

• .s the ostium secundum enlarges# the septum secundum makes itsappearance ad!acent to the septum primum" – 2his septum secundum proliferates to form a crescent/shaped structure

overlapping a space termed the foramen ovale.

• 2he foramen ovale is closed on its left side by a flap of tissue derived fromthe primary septum:

– this flap acts as a one/way valve that allows right/to/left blood flow duringintrauterine life"

• .t the time of birth# falling pulmonary vascular resistance and risingsystemic arterial pressure causes left atrial pressures to e%ceed those inthe right atrium:

– result is a functional closure of the foramen ovale"

• 9n most individuals the foramen ovale is permanently sealed by fusion of theprimary and secondary septa# although a

– minor degree of patency persists in about *-' of the general population"





• .bnormalities in this se8uence result in the developmentof the various .SDs:

– three types are recogniBed – ostium secundum "S#

• 2he most common 10+' is the, which

• occurs when the septum secundum does not enlarge sufficiently tocover the ostium secundum

– $stium primum "S#s are• less common 1-' of cases: these

• occur if the septum primum and endocardial cushion fail to fuse andare often associated with abnormalities in other structures derivedfrom the endocardial cushion 1e"g"# mitral and tricuspid valves"

– 2he sinus venosus "S#s

• 1-' of cases are located near the entrance of the superior venacava and have been

• associated with frameshift mutations in the 745*"- transcriptionfactor"







• (orphology – Ostium secundum

• .SDs are typically smooth/walled defects near the foramen ovale#

• usually without other associated cardiac abnormalities" )ecause of the• left/to/right shunt# hemodynamically significant lesions are accompanied byincreased volume load on the right side of the heart

– right atrial and ventricular dilation# right ventricular hypertrophy# and dilation of thepulmonary artery

– Ostium primum • .SDs occur at the lowest part of the atrial septum• can e%tend to the mitral and tricuspid valves# reflecting the close relationship

between development of the septum primum and endocardial cushion"• .bnormalities of the atrioventricular valves are usually present# typically in

the form of a cleft in the anterior leaflet of the mitral valve or septal leaflet ofthe tricuspid valve"

• 9n more severe cases# the ostium primum defect is accompanied by a >SDand severe mitral and tricuspid valve deformities# with a resultant commonatrioventricular canal"

– Sinus venosus • .SDs are located high in the atrial septum• often accompanied by anomalous drainage of the pulmonary veins into the

right atrium or superior vena cava"



• Clinical <eatures – .SDs

• most common defects to be first diagnosed in adults"• less likely to spontaneously close• left/to/right shunts# as a result of the

– lower pressures in the pulmonary circulation and right side of the heart"well tolerated# especially if they are less than & cm in diameter: evenlarger lesions do not usually produce any symptoms in childhood"

• ith time# however# pulmonary vascular resistance can increase#

resulting in pulmonary hypertension" – less than &+' of patients with uncorrected .SD"

• 2he ob!ectives of surgical closure of .SDs are: – reversal of the hemodynamic abnormalities and the – prevention of complications# including heart failure# parado%ical

emboliBation# and irreversible pulmonary vascular disease"

• (ortality is low

– postoperative survival is comparable to that of a normal population"• 6stium primum defects are more likely to be associated with

evidence of CH<# in part because of the high fre8uency ofassociated mitral insufficiency"



• >SDs – 9ncomplete closure of the ventricular septum allows left/to/right

shunting – (ost common congenital cardiac anomaly at birth

– 7ormally formed by the fusion of:• an intraventricular muscular ridge that grows upward from the ape%

of the heart with

• a thinner membranous partition that grows downward from the

endocardial cushion"

– 2he basal 1membranous region is the site of appro%imately 0+'of >SDs

• last part of the septum to develop

– 6verall incidence in adults is lower than that of .SDs

• more common at birth than .SDs#• most >SDs close spontaneously in childhood#

– Commonly associated with other cardiac malformations• Aoughly 3+' of >SDs occur in isolation







• (orphology

– SiBe and location of >SDs are variable:• minute defects in the muscular or membranous

portions of the septum

• large defects involving virtually the entire septum"

– Defects with a significant left/to/right shunt:• right ventricle is hypertrophied and often dilated

– 2he diameter of the pulmonary artery isincreased:

• increased volume e!ected by the right ventricle" – >ascular changes typical of pulmonary

hypertension are common



• Clinical <eatures – Small >SDs:

• may be asymptomatic• those in the muscular portion of the septum may close

spontaneously during infancy or childhood"

– @arger defects:• severe left/to/right shunt#

• often complicated by pulmonary hypertension and CH<"• Progressive pulmonary hypertension:

– resultant reversal of the shunt and cyanosis#

– earlier and more common in patients with >SDs than .SDs:

– 7eeds early surgical correction

– Small/ or medium/siBed defects:• produce !et lesions in the right ventricle

• prone to superimposed infective endocarditis"



• Patent ductus arteriosus – During intrauterine life:

• blood flow from the pulmonary artery to the aorta

• bypassing the uno%ygenated lungs – Shortly after birth: the ductus constricts in response to:

• increased arterial o%ygenation#

• decreased pulmonary vascular resistance# and

• declining local levels of prostaglandin *"

– 9n healthy term infants• functionally nonpatent within & to * days after birth:

• complete# structural obliteration occurs within the first few months ofe%trauterine life to form the ligamentum arteriosum.

– Ductal closure is often delayed 1or even absent in infants withhypo%ia

• resulting from respiratory distress or heart disease – PD.s account for about ,' of cases of congenital heart lesions:

• 0+' are isolated defects

• remaining occur with other congenital defects# most commonly >SDs"







• (orphology

– 2he ductus arteriosus arises from the left

pulmonary artery and !oins the aorta !ust distal tothe origin of the left subclavian artery"

– Pro%imal pulmonary arteries# left atrium# andventricle can become dilated

• 9n PD.s some of the o%ygenated blood flowing outfrom the left ventricle is shunted back to the lungs

• resultant volume overload

– Aight heart hypertrophy and dilation"

• ith the development of pulmonary hypertension#

• atherosclerosis of the main pulmonary arteries andproliferative changes in more distal pulmonary vessels



• Clinical <eatures – PD.s:

• high/pressure left/to/right shunts#

• audible as harsh Emachinery/likeE murmurs" – . small PD. / no symptoms – larger bore defects / lead to the isenmenger syndrome

with cyanosis and CH<" – 2he high/pressure shunt also predisposes affected

individuals to infective endocarditis – 2here is general agreement that isolated PD.s should be

closed as early in life as is feasible# – Preservation of ductal patency

• by administering prostaglandin

• critically important for infants with various forms of congenitalheart disease wherein the• PD. is the only means to provide systemic or pulmonary blood

flow 1e"g"# aortic or pulmonic atresia"

– 9ronically# then# the ductus can be either life threateningor lifesaving"



• Aight/to/@eft Shunts – Cardiac malformations associated with right/to/left shunts

are distinguished by

• cyanosis at or near the time of birth. • poorly o%ygenated blood from the right side of the heart isintroduced directly into the arterial circulation"

– 2wo of the most important conditions associated withcyanotic congenital heart disease are:

• tetralogy of %allot

• transposition of the great vessels 1<ig" – Clinical findings associated with severe# long/standing

cyanosis:• clubbing of the fingertips (hypertrophic osteoarthropathy) and

polycythemia

– 9n addition# right/to/left shunts permit venous emboli tobypass the lungs and directly enter the systemiccirculation

• parado&ical embolism



• 2etralogy of <allot – -' of all congenital cardiac malformations# tetralogy of %allot

– most common cause of cyanotic congenital heart disease – 2he four features of the tetralogy are:

1& >SD#

1* obstruction to the right ventricular outflow tract 1subpulmonicstenosis#

13 an aorta that overrides the >SD# and

1F right ventricular hypertrophy

– .ll of the features result from anterosuperior displacement of theinfundibular septum# so that there is

• abnormal division into the pulmonary trunk and aortic root"

– ven untreated# some tetralogy patients can survive into adult

life – Clinical severity largely depends on the degree of the pulmonary

outflow obstruction"







• (orphology – 2he heart is large and Eboot shapedE in tetralogy of

<allot as a result of:• right ventricular hypertrophy:• the pro%imal aorta is typically larger than normal# with a

diminished pulmonary trunk"• 2he left/sided cardiac chambers are normal siBed# while the

right ventricular wall is markedly thickened and may even

e%ceed that of the left"• 2he >SD lies in the vicinity of the membranous portion of theinterventricular septum# and the aortic valve lies immediatelyover the >SD

• 2he pulmonary outflow tract is narrowed# and# in a fewcases# the pulmonic valve may be stenotic

– .dditional abnormalities are present in many cases#including PD. or .SD:• actually beneficial in many respects# because they permit

pulmonary blood flow"



• Clinical <eatures – 2he hemodynamic conse8uences of tetralogy of <allot are:

• right/to/left shunting#

• decreased pulmonary blood flow#• increased aortic volumes"

– 'he e&tent of shunting 1and the clinical severity is determined by theamount of right ventricular outflo obstruction.

• 9f the pulmonic obstruction is mild# the condition resembles an isolated >SD# – because the high left/sided pressures on the left side cause a left/to/right shunt

with no cyanosis"

• (ore commonly# marked stenosis causes significant right/to/left shunting – conse8uent cyanosis early in life"

• .s patients with tetralogy grow# the pulmonic orifice does not enlarge#despite an overall increase in the siBe of the heart"

– Hence# the degree of stenosis typically worsens with time resulting in increasingcyanosis"

• 2he lungs are protected from hemodynamic overload by the pulmonicstenosis# so that pulmonary hypertension does not develop"

– .s with any cyanotic heart disease# patients develop erythrocytosis withattendant hyperviscosity# and hypertrophic osteoarthropathy: the right/to/left shunting also increases the risk for infective endocarditis#systemic emboli# and brain abscesses"

– Surgical correction of this defect is now possible in most instances"



• 2ransposition of the $reat .rteries – Discordant connection of the ventricles to

their vascular outflow

– 2he embryologic defect• abnormal formation of the truncal and

aortopulmonary septa:

• aorta arises from the right ventricle and the• pulmonary artery emanates from the left ventricle

1<ig"

– 2he atrium/to/ventricle connections are

normal 1concordant• right atrium !oining right ventricle and

• left atrium emptying into left ventricle"





• 2he functional outcome:

– separation of the systemic and pulmonarycirculations

– a condition incompatible with postnatal life• shunt e%ists for ade8uate mi%ing of blood and

delivery of o%ygenated blood to the aorta"

– stable shunt 13-'• Patients with 2$. and a >SD

– unstable shunts 1G-'• Patients with only a patent foramen ovale or PD.

• can close and often re8uire surgical interventionwithin the first few days of life"



• (orphology

– 2$. has many variants:

• abnormal origin of the pulmonary trunk and aorticroot

• patients surviving beyond the neonatal period:

– >arying combinations of .SD# >SD# and PD.

• Aight ventricular hypertrophy:

– functions as the systemic ventricle

• @eft ventricle becomes somewhat atrophic: – support the low/resistance pulmonary circulation



• Clinical <eatures – arly cyanosis

• predominant manifestation of 2$.

– 2he outlook for neonates with 2$. depends on:• the degree of the shunting

• the magnitude of the tissue hypo%ia

• the ability of the right ventricle to maintain systemic pressures"

– Procedures that enhance arterial o%ygen saturation:• 9nfusions of prostaglandin *

– maintain patency of the ductus arteriosus

• .trial septostomy – create .SDs

– ven with stable shunting# most uncorrected 2$.patients still die within the first months of life"

– Conse8uently# affected individuals usually undergocorrective surgery 1switching the great arteries withinweeks of birth"



• Congenital 6bstructive @esions

– 6bstruction to blood flow can occur at the

level of the heart valves or within a greatvessel"

– 6bstruction can also occur within a chamber

• subpulmonic stenosis in tetralogy of <allot"

– Aelatively common e%amples of congenitalobstruction include:

• pulmonic valve stenosis#

• aortic valve stenosis or atresia• coarctation of the aorta"



• .ortic Coarctation – relatively common structural anomaly – most important form of obstructive congenital heart

disease" – (ales are affected twice as often as females:

• females with 2urner syndrome fre8uently have aortic coarctation

– 2wo classic forms have been described 1<ig;• EinfantileE form with hypoplasia of the aortic arch pro%imal to a

PD.# and an• EadultE form in which there is a discrete ridgelike infolding of the

aorta# !ust opposite the ligamentum arteriosum distal to the archvessels"

– Coarctation of the aorta may occur as a solitary defect – more than -+' of cases# it is accompanied by a bicuspid

aortic valve"• Congenital aortic stenosis# .SD# >SD# or mitral regurgitation may

also occur"• 9n some cases berry aneurysms in the circle of illis coe%ist"





• (orphology – Preductal 1EinfantileE coarctation:

• tubular narrowing of the aortic segment between the left

subclavian artery and the ductus arteriosus• usually patent• main source of blood delivered to the distal aorta"• )ecause the right side of the heart must perfuse the body distal

to the narrowing# the – right ventricle is typically hypertrophied and dilated

– pulmonary trunk is also dilated to accommodate the increased bloodflow"

– Postductal 1EadultE coarctation:• more common• sharply constricted by a ridge of tissue at or !ust distal to the

ligamentum arteriosum

– made up of smooth muscle and elastic fibers that are continuouswith the aortic media and are lined by a thickened layer of intima"

• 2he ductus arteriosus is closed"• Pro%imal to the coarct# the aortic arch and its branch vessels are

dilated and# in older patients# often atherosclerotic• left ventricle is hypertrophic"



• Clinical <eatures – depend almost entirely on the severity of the narrowing and the patency

of the ductus arteriosus" – reductal coarctation of the aorta ith a #"!

• usually leads to manifestations early in life# hence the older designation ofinfantile coarctation

• cause signs and symptoms immediately after birth"• delivery of poorly o%ygenated blood through the ductus arteriosus produces

cyanosis localiBed to the lower half of the body"• <emoral pulses are almost always weaker than those of the upper

e%tremeties"

• (any such infants do not survive the neonatal period without intervention – ostductal coarctation of the aorta ithout a #"!

• usually asymptomatic# and the disease may go unrecogniBed until well intoadult life

• upper e%tremity hypertension# due to poor perfusion of the kidneys# but weakpulses and a lower blood pressure in the lower e%tremities"

• Claudication and coldness of the lower e%tremeties result from arterial

insufficiency"• .dults tend to show e%uberant collateral circulation EaroundE the coarctationinvolving markedly enlarged intercostal and internal mammary arteries:

• e%pansion of the flow through these vessels leads to radiographically visibleEnotchingE of the ribs"



S((.AI

• Congenital Heart Disease – Defects of cardiac chambers or the great vessels: – Shunting of blood between the right and left circulation or cause outflow

obstructions" – @eft/to/right shunts

• most common and typically involve• .SDs# >SDs# or a PD." 2hese lesions• result in chronic right/sided pressure and volume overload that eventually

causes pulmonary hypertension with reversal of flow and right/to/left shuntswith cyanosis 1isenmenger syndrome"

– Aight/to/left shunts• tetralogy of <allot or transposition of great vessels•

cyanotic lesions from the outset and are associated with polycythemia#hypertrophic osteoarthropathy# and parado%ical emboli"

– 6bstructive lesions include aortic coarctation: the• clinical severity of the lesion depends the degree of stenosis and the

patency of the ductus arteriosus"



Congenital Heart Disease

. general term to describe abnormalities of

the heart or great vessels that are presentfrom birth"



Congenital Heart Disease

2hree ma!or categories;*.left-to-right shunt

("cyanotic heart disease)

+.right-to-left shunt(yanotic heart disease)

.obstruction(Stenosis "tresia)



.cyanotic Heart Disease

.trial Septal Defect 1.SD#

>entricular Septal Defect 1>SD#

Patent Ductus .rteriosus 1PD .# and

.trioventricular Septal Defect

1.>SD"



>entricular Septal Defect 1>SD

Atrial Septal Defect



Atrial Septal Defect

(ASD)



Cyanotic Heart Disease

Tetralogy of <allot 126<

Transposition of great arteries12$.

Truncus .rteriosus

Tricuspid .tresiaTotal .nomalous Pulmonary

>enous Connection 12.P>C

T t l f F ll t



Tetralogy of Fallot



Transposition of the Great Arteries

Tricuspid Atresia



Tricuspid Atresia

Truncus Arteriosus



Truncus Arteriosus



ObstructiveCongenitalAnomalies

&" Coarctation of .orta

*" Pulmonary Stenosis and

.tresia

3" .ortic Stenosis and .tresia

ulmonary !alve



ulmonary !alve

Stenosis and Atresia

Hypoplastic "eft Heart



Hypoplastic "eft Heart

Syndrome



• Teachers

open thedoor but you

must walkthrough ityourself.





2hanks

Documents

Lec 2, Congenital Heart Diseases