2Congenital heart diseases abnormalities of the heart or great vessels that are present at birthfaulty embryogenesis during gestational weeks 3 through 8major 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 adult life.Generally accepted incidence is approximately 1% of live birthshigher in premature infants and in stillborns.Most common type of heart disease among children.
3Patients surviving with congenital heart disease is increasing rapidly Because of clinical advancesby 2020 there will be an estimated 750,000 adults with congenital heart disease.Surgery can correct the hemodynamic abnormalitiesrepaired heart may still not be completely normalAlthough adaptive initially, such changes can elicit late-onset arrhythmias, ischemia, or myocardial dysfunction, sometimes many years after surgeryMyocardial hypertrophy and a cardiac remodeling brought about by the congenital defect may be irreversible.
4General concepts regarding the etiology of congenital malformations unknown in almost 90% of cases.Environmental factors,congenital rubella infection, are causal in many instances.Genetic factors are also clearly involved,as evidenced by familial forms of congenital heart diseasewell-defined associations with certain chromosomal abnormalities (e.g., trisomies 13, 15, 18, and 21 and Turner syndrome).
5Cardiac morphogenesis involves multiple genestightly regulated to ensure an effective embryonic circulation.Key steps involve specifying cardiac cell fate, morphogenesis and looping of the heart tube, segmentation and growth of the cardiac chambers, cardiac valve formation, and connection of the great vessels to the heart.The molecular pathways controlling such cardiac developmentprovide a foundation for understanding the basis of some congenital heart defects.Several congenital heart diseases are associated with mutations in transcription factors.Mutations of the TBX5 transcription factor cause the atrial and ventricular septal defects seen in Holt-Oram syndrome.Mutations in the transcription factor NKX2.5 are associated with isolated atrial septal defects (ASDs).
6Since different cardiac structures can share the same developmental pathways, dissimilar lesions may be related to a common genetic defectThe unifying feature of many outflow tract defects is the abnormal development of neural crest-derived cells,whose migration into the embryonic heart is required for outflow tract formation.In particular, genes located on chromosome 22 have a major role in forming the conotruncus, the branchial arches, and the human face;Now known that deletions of chromosome 22q11.2 underlie 15% to 50% of outflow tract abnormalities.can also cause developmental anomalies of the fourth branchial arch and derivatives of the third and fourth pharyngeal pouchesleading to thymic and parathyroid hypoplasiaresultant immune deficiency (Di George syndrome) and hypocalcemia.
7Congenital heart diseases can be subdivided into three major groups: Twelve disorders account for 85% of congenital heart disease; their frequencies are shown in Table.Congenital heart diseases can be subdivided into three major groups:Malformations causing a left-to-right shuntMalformations causing a right-to-left shunt (cyanotic congenital heart diseases)Malformations causing obstruction
8MalformationIncidence per Million Live Births%Ventricular septal defect448242Atrial septal defect104310Pulmonary stenosis8368Patent ductus arteriosus7817Tetralogy of Fallot5775Coarctation of the aorta492Atrioventricular septal defect3964Aortic stenosis388Transposition of the great arteriesTruncus arteriosus1361Total anomalous pulmonary venous connection120Tricuspid atresia118TOTAL9757Frequencies of Congenital Cardiac Malformations
9Shunt 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 (or vice versa).Right-to-left shuntdusky blueness of the skin (cyanosis) resultspulmonary circulation is bypassedpoorly oxygenated blood enters the systemic circulation.Left-to-right shuntsincrease pulmonary blood flownot associated (at least initially) with cyanosisexpose the low-pressure, low-resistance pulmonary circulation to increased pressure and volume, resulting in right ventricular hypertrophy and-eventually-right-sided failure.obstructive congenital heart diseaseSome developmental anomalies obstruct vascular flow by narrowing the chambers, valves, or major blood vessels;A complete obstruction is called an atresia.In some disorders (e.g., tetralogy of Fallot), an obstruction (pulmonary stenosis) is associated with a shunt (right-to-left through a ventricular septal defect [VSD]).
10Left-to-right shunts; most common type of congenital cardiac malformation (Fig.)atrial and ventricular septal defects, and patent ductus arteriosus.Atrial septal defects are typically associated with increased pulmonary blood volumesventricular septal defects and patent ductus arteriosus result in both increased pulmonary blood flow and pressure.These malformations can be asymptomatic or can cause fulminant CHF at birth.Cyanosis is not an early feature of these defects, but it can occur late,Eisenmenger syndrome.after prolonged left-to-right shunting has produced pulmonary hypertension sufficient to yield right-sided pressures that exceed those on the left and thus result in a reversal of blood flow through the shuntRationale for early intervention, either surgical or nonsurgicalOnce significant pulmonary hypertension develops,structural defects of congenital heart disease are considered irreversible
12ASDs normal atrial septation (Fig.) begins as an ingrowth of the septum primum from the dorsal wall of the common 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 septumallowing continued flow of oxygenated blood from the right to left atria, essential for fetal lifeAs the ostium secundum enlarges, the septum secundum makes its appearance adjacent to the septum primum.This septum secundum proliferates to form a crescent-shaped structure overlapping a space termed the foramen ovale.The foramen ovale is closed on its left side by a flap of tissue derived from the primary septum;this flap acts as a one-way valve that allows right-to-left blood flow during intrauterine life.At the time of birth, falling pulmonary vascular resistance and rising systemic arterial pressure causes left atrial pressures to exceed those in the right atrium;result is a functional closure of the foramen ovale.In most individuals the foramen ovale is permanently sealed by fusion of the primary and secondary septa, although aminor degree of patency persists in about 25% of the general population.
14Abnormalities in this sequence result in the development of the various ASDs; three types are recognizedostium secundum ASDThe most common (90%) is the, whichoccurs when the septum secundum does not enlarge sufficiently to cover the ostium secundumOstium primum ASDs areless common (5% of cases); theseoccur if the septum primum and endocardial cushion fail to fuse and are often associated with abnormalities in other structures derived from the endocardial cushion (e.g., mitral and tricuspid valves).The sinus venosus ASDs(5% of cases) are located near the entrance of the superior vena cava and have beenassociated with frameshift mutations in the NKX2.5 transcription factor.
15Pathophysiology of atrial septal defect Pathophysiology of atrial septal defect. The net left-to-right shunt through the atrial septal defect results in volume overload of the right atrium, right ventricle, and pulmonary circulation. The volume of the shunt can be calculated from cardiac output and the amount of increase in oxygen saturation occurring at right atrial level. In the early stages, the pressures in the right side of the heart are not increased. With time, pulmonary vascular changes may occur, leading to increasing pulmonary arterial pressure. Reversal of the direction of flow through the shunt may occur with severe pulmonary hypertension.
17Morphology Ostium secundum Ostium primum Sinus venosus ASDs are typically smooth-walled defects near the foramen ovale,usually without other associated cardiac abnormalities. Because of theleft-to-right shunt, hemodynamically significant lesions are accompanied by increased volume load on the right side of the heartright atrial and ventricular dilation, right ventricular hypertrophy, and dilation of the pulmonary arteryOstium primumASDs occur at the lowest part of the atrial septumcan extend to the mitral and tricuspid valves, reflecting the close relationship between development of the septum primum and endocardial cushion.Abnormalities 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 of the tricuspid valve.In more severe cases, the ostium primum defect is accompanied by a VSD and severe mitral and tricuspid valve deformities, with a resultant common atrioventricular canal.Sinus venosusASDs are located high in the atrial septumoften accompanied by anomalous drainage of the pulmonary veins into the right atrium or superior vena cava.
18Clinical Features ASDs most common defects to be first diagnosed in adults.less likely to spontaneously closeleft-to-right shunts, as a result of thelower pressures in the pulmonary circulation and right side of the heart. well tolerated, especially if they are less than 1 cm in diameter; even larger lesions do not usually produce any symptoms in childhood.With time, however, pulmonary vascular resistance can increase, resulting in pulmonary hypertension.less than 10% of patients with uncorrected ASD.The objectives of surgical closure of ASDs are;reversal of the hemodynamic abnormalities and theprevention of complications, including heart failure, paradoxical embolization, and irreversible pulmonary vascular disease.Mortality is lowpostoperative survival is comparable to that of a normal population.Ostium primum defects are more likely to be associated with evidence of CHF, in part because of the high frequency of associated mitral insufficiency.
19VSDsIncomplete closure of the ventricular septum allows left-to-right shuntingMost common congenital cardiac anomaly at birthNormally formed by the fusion of;an intraventricular muscular ridge that grows upward from the apex of the heart witha thinner membranous partition that grows downward from the endocardial cushion.The basal (membranous) region is the site of approximately 90% of VSDslast part of the septum to developOverall incidence in adults is lower than that of ASDsmore common at birth than ASDs,most VSDs close spontaneously in childhood,Commonly associated with other cardiac malformationsRoughly 30% of VSDs occur in isolation
20Pathophysiology of ventricular septal defect Pathophysiology of ventricular septal defect. The defect results in a left-to-right shunt at the ventricular level, resulting in increased volume and pressure in the right ventricle, the magnitude of which depends on the size of the defect. The right ventricle undergoes hypertrophy because of volume and pressure overload. The left ventricle, which must handle the shunted blood in addition to the normal output into the aorta, also undergoes hypertrophy and dilation. Pulmonary arterial pressure may increase with time as a result of changes occurring in the pulmonary vasculature. This causes a progressive decrease in shunt volume and, if severe enough, may result in shunt reversal.
22Morphology Size and location of VSDs are variable; minute defects in the muscular or membranous portions of the septumlarge defects involving virtually the entire septum.Defects with a significant left-to-right shunt;right ventricle is hypertrophied and often dilatedThe diameter of the pulmonary artery is increased;increased volume ejected by the right ventricle.Vascular changes typical of pulmonary hypertension are common
23Clinical Features Small VSDs; Larger defects; may be asymptomaticthose in the muscular portion of the septum may close spontaneously during infancy or childhood.Larger defects;severe left-to-right shunt,often complicated by pulmonary hypertension and CHF.Progressive pulmonary hypertension;resultant reversal of the shunt and cyanosis,earlier and more common in patients with VSDs than ASDs;Needs early surgical correctionSmall- or medium-sized defects;produce jet lesions in the right ventricleprone to superimposed infective endocarditis.
24Patent ductus arteriosus During intrauterine life;blood flow from the pulmonary artery to the aortabypassing the unoxygenated lungsShortly after birth; the ductus constricts in response to;increased arterial oxygenation,decreased pulmonary vascular resistance, anddeclining local levels of prostaglandin E2.In healthy term infantsfunctionally nonpatent within 1 to 2 days after birth;complete, structural obliteration occurs within the first few months of extrauterine life to form the ligamentum arteriosum.Ductal closure is often delayed (or even absent) in infants with hypoxiaresulting from respiratory distress or heart diseasePDAs account for about 7% of cases of congenital heart lesions;90% are isolated defectsremaining occur with other congenital defects, most commonly VSDs.
25Pathophysiology of patent ductus arteriosus Pathophysiology of patent ductus arteriosus. Blood is shunted from the aorta to the main pulmonary artery via the patent ductus. This results in increased pressure and volume in the pulmonary artery, the magnitude of which depends on the size of the shunt. Pulmonary hypertension causes right ventricular hypertrophy. The left ventricle, which pumps a volume equal to the shunt plus the systemic output, also undergoes hypertrophy. Increasing pulmonary hypertension due to secondary pulmonary vascular changes may result in shunt reversal.
27MorphologyThe ductus arteriosus arises from the left pulmonary artery and joins the aorta just distal to the origin of the left subclavian artery.Proximal pulmonary arteries, left atrium, and ventricle can become dilatedIn PDAs some of the oxygenated blood flowing out from the left ventricle is shunted back to the lungsresultant volume overloadRight heart hypertrophy and dilation.With the development of pulmonary hypertension,atherosclerosis of the main pulmonary arteries and proliferative changes in more distal pulmonary vessels
28Clinical Features PDAs; A small PDA - no symptoms high-pressure left-to-right shunts,audible as harsh "machinery-like" murmurs.A small PDA - no symptomslarger bore defects - lead to the Eisenmenger syndrome with cyanosis and CHF.The high-pressure shunt also predisposes affected individuals to infective endocarditisThere is general agreement that isolated PDAs should be closed as early in life as is feasible,Preservation of ductal patencyby administering prostaglandin Ecritically important for infants with various forms of congenital heart disease wherein thePDA is the only means to provide systemic or pulmonary blood flow (e.g., aortic or pulmonic atresia).Ironically, then, the ductus can be either life threatening or lifesaving.
29Right-to-Left ShuntsCardiac malformations associated with right-to-left shunts are distinguished bycyanosis at or near the time of birth.poorly oxygenated blood from the right side of the heart is introduced directly into the arterial circulation.Two of the most important conditions associated with cyanotic congenital heart disease are;tetralogy of Fallottransposition of the great vessels (Fig.)Clinical findings associated with severe, long-standing cyanosis;clubbing of the fingertips (hypertrophic osteoarthropathy) and polycythemiaIn addition, right-to-left shunts permit venous emboli to bypass the lungs and directly enter the systemic circulationparadoxical embolism
30Tetralogy of Fallot5% of all congenital cardiac malformations, tetralogy of Fallotmost common cause of cyanotic congenital heart diseaseThe four features of the tetralogy are;(1) VSD,(2) obstruction to the right ventricular outflow tract (subpulmonic stenosis),(3) an aorta that overrides the VSD, and(4) right ventricular hypertrophyAll of the features result from anterosuperior displacement of the infundibular septum, so that there isabnormal division into the pulmonary trunk and aortic root.Even untreated, some tetralogy patients can survive into adult lifeClinical severity largely depends on the degree of the pulmonary outflow obstruction.
31Tetralogy of Fallot. The marked narrowing of the pulmonary outflow tract results in a right-to-left shunt through the ventricular septal defect, resulting in central cyanosis. The right ventricle is hypertrophied.
33MorphologyThe heart is large and "boot shaped" in tetralogy of Fallot as a result of;right ventricular hypertrophy;the proximal aorta is typically larger than normal, with a diminished pulmonary trunk.The left-sided cardiac chambers are normal sized, while the right ventricular wall is markedly thickened and may even exceed that of the left.The VSD lies in the vicinity of the membranous portion of the interventricular septum, and the aortic valve lies immediately over the VSDThe pulmonary outflow tract is narrowed, and, in a few cases, the pulmonic valve may be stenoticAdditional abnormalities are present in many cases, including PDA or ASD;actually beneficial in many respects, because they permit pulmonary blood flow.
34Clinical FeaturesThe hemodynamic consequences of tetralogy of Fallot are;right-to-left shunting,decreased pulmonary blood flow,increased aortic volumes.The extent of shunting (and the clinical severity) is determined by the amount of right ventricular outflow obstruction.If the pulmonic obstruction is mild, the condition resembles an isolated VSD,because the high left-sided pressures on the left side cause a left-to-right shunt with no cyanosis.More commonly, marked stenosis causes significant right-to-left shuntingconsequent cyanosis early in life.As patients with tetralogy grow, the pulmonic orifice does not enlarge, despite an overall increase in the size of the heart.Hence, the degree of stenosis typically worsens with time resulting in increasing cyanosis.The lungs are protected from hemodynamic overload by the pulmonic stenosis, so that pulmonary hypertension does not develop.As with any cyanotic heart disease, patients develop erythrocytosis with attendant 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.
35Transposition of the Great Arteries Discordant connection of the ventricles to their vascular outflowThe embryologic defectabnormal formation of the truncal and aortopulmonary septa;aorta arises from the right ventricle and thepulmonary artery emanates from the left ventricle (Fig.)The atrium-to-ventricle connections are normal (concordant)right atrium joining right ventricle andleft atrium emptying into left ventricle.
37The functional outcome; separation of the systemic and pulmonary circulationsa condition incompatible with postnatal lifeshunt exists for adequate mixing of blood and delivery of oxygenated blood to the aorta.stable shunt (35%)Patients with TGA and a VSDunstable shunts (65%)Patients with only a patent foramen ovale or PDAcan close and often require surgical intervention within the first few days of life.
38Morphology TGA has many variants; abnormal origin of the pulmonary trunk and aortic rootpatients surviving beyond the neonatal period;Varying combinations of ASD, VSD, and PDARight ventricular hypertrophy;functions as the systemic ventricleLeft ventricle becomes somewhat atrophic;support the low-resistance pulmonary circulation
39Clinical Features Early cyanosis predominant manifestation of TGAThe outlook for neonates with TGA depends on;the degree of the shuntingthe magnitude of the tissue hypoxiathe ability of the right ventricle to maintain systemic pressures.Procedures that enhance arterial oxygen saturation;Infusions of prostaglandin E2maintain patency of the ductus arteriosusAtrial septostomycreate ASDsEven with stable shunting, most uncorrected TGA patients still die within the first months of life.Consequently, affected individuals usually undergo corrective surgery (switching the great arteries) within weeks of birth.
40Congenital Obstructive Lesions Obstruction to blood flow can occur at the level of the heart valves or within a great vessel.Obstruction can also occur within a chambersubpulmonic stenosis in tetralogy of Fallot.Relatively common examples of congenital obstruction include;pulmonic valve stenosis,aortic valve stenosis or atresiacoarctation of the aorta.
41Aortic Coarctation relatively common structural anomaly most important form of obstructive congenital heart disease.Males are affected twice as often as females;females with Turner syndrome frequently have aortic coarctationTwo classic forms have been described (Fig):"infantile" form with hypoplasia of the aortic arch proximal to a PDA, and an"adult" form in which there is a discrete ridgelike infolding of the aorta, just opposite the ligamentum arteriosum distal to the arch vessels.Coarctation of the aorta may occur as a solitary defectmore than 50% of cases, it is accompanied by a bicuspid aortic valve.Congenital aortic stenosis, ASD, VSD, or mitral regurgitation may also occur.In some cases berry aneurysms in the circle of Willis coexist.
43Morphology Preductal ("infantile") coarctation; tubular narrowing of the aortic segment between the left subclavian artery and the ductus arteriosususually patentmain source of blood delivered to the distal aorta.Because the right side of the heart must perfuse the body distal to the narrowing, theright ventricle is typically hypertrophied and dilatedpulmonary trunk is also dilated to accommodate the increased blood flow.Postductal ("adult") coarctation;more commonsharply constricted by a ridge of tissue at or just distal to the ligamentum arteriosummade up of smooth muscle and elastic fibers that are continuous with the aortic media and are lined by a thickened layer of intima.The ductus arteriosus is closed.Proximal to the coarct, the aortic arch and its branch vessels are dilated and, in older patients, often atheroscleroticleft ventricle is hypertrophic.
44Clinical Featuresdepend almost entirely on the severity of the narrowing and the patency of the ductus arteriosus.Preductal coarctation of the aorta with a PDA;usually leads to manifestations early in life, hence the older designation of infantile coarctationcause signs and symptoms immediately after birth.delivery of poorly oxygenated blood through the ductus arteriosus produces cyanosis localized to the lower half of the body.Femoral pulses are almost always weaker than those of the upper extremeties.Many such infants do not survive the neonatal period without interventionPostductal coarctation of the aorta without a PDA;usually asymptomatic, and the disease may go unrecognized until well into adult lifeupper extremity hypertension, due to poor perfusion of the kidneys, but weak pulses and a lower blood pressure in the lower extremities.Claudication and coldness of the lower extremeties result from arterial insufficiency.Adults tend to show exuberant collateral circulation "around" the coarctation involving markedly enlarged intercostal and internal mammary arteries;expansion of the flow through these vessels leads to radiographically visible "notching" of the ribs.
45SUMMARY Congenital Heart Disease Defects of cardiac chambers or the great vessels;Shunting of blood between the right and left circulation or cause outflow obstructions.Left-to-right shuntsmost common and typically involveASDs, VSDs, or a PDA. These lesionsresult in chronic right-sided pressure and volume overload that eventually causes pulmonary hypertension with reversal of flow and right-to-left shunts with cyanosis (Eisenmenger syndrome).Right-to-left shuntstetralogy of Fallot or transposition of great vesselscyanotic lesions from the outset and are associated with polycythemia, hypertrophic osteoarthropathy, and paradoxical emboli.Obstructive lesions include aortic coarctation; theclinical severity of the lesion depends the degree of stenosis and the patency of the ductus arteriosus.
46Congenital Heart Disease A general term to describe abnormalities of the heart or great vessels that are present from birth.
47Congenital Heart Disease Three major categories:left-to-right shunt (Acyanotic heart disease)right-to-left shunt (Cyanotic heart disease)obstruction (Stenosis / Atresia)47