Congenital Heart Diseases

1. Congenital Heart Diseases Special Pathology

2. Congenital heart diseases • abnormalities of the heart or great vessels that are present at birth • faulty embryogenesis during gestational weeks 3 through 8 • major 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 births • higher in premature infants and in stillborns. • Most common type of heart disease among children.

3. Patients surviving with congenital heart disease is increasing rapidly • Because of clinical advances • by 2020 there will be an estimated 750,000 adults with congenital heart disease. • Surgery can correct the hemodynamic abnormalities • repaired heart may still not be completely normal • Although adaptive initially, such changes can elicit late-onset arrhythmias, ischemia, or myocardial dysfunction, sometimes many years after surgery • Myocardial hypertrophy and a cardiac remodeling brought about by the congenital defect may be irreversible.

4. General 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 disease • well-defined associations with certain chromosomal abnormalities (e.g., trisomies 13, 15, 18, and 21 and Turner syndrome).

5. Cardiac morphogenesis • involves multiple genes • tightly 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 development • provide 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).

6. Since different cardiac structures can share the same developmental pathways, • dissimilar lesions may be related to a common genetic defect • The 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 pouches • leading to thymic and parathyroid hypoplasia • resultant immune deficiency (Di George syndrome) and hypocalcemia.

7. 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 shunt • Malformations causing a right-to-left shunt (cyanotic congenital heart diseases) • Malformations causing obstruction

9. 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 (or vice versa). • Right-to-left shunt • dusky blueness of the skin (cyanosis) results • pulmonary circulation is bypassed • poorly oxygenated blood enters the systemic circulation. • Left-to-right shunts • increase pulmonary blood flow • not associated (at least initially) with cyanosis • expose 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 disease • Some 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]).

10. Left-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 volumes • ventricular 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 shunt • Rationale for early intervention, either surgical or nonsurgical • Once significant pulmonary hypertension develops, • structural defects of congenital heart disease are considered irreversible

12. ASDs • 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 septum • allowing continued flow of oxygenated blood from the right to left atria, essential for fetal life • As 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 a • minor degree of patency persists in about 25% of the general population.

14. Abnormalities in this sequence result in the development of the various ASDs; • three types are recognized • ostium secundum ASD • The most common (90%) is the, which • occurs when the septum secundum does not enlarge sufficiently to cover the ostium secundum • Ostium primum ASDs are • less common (5% of cases); these • occur 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 been • associated with frameshift mutations in the NKX2.5 transcription factor.

17. Morphology • Ostium secundum • ASDs are typically smooth-walled defects near the foramen ovale, • usually without other associated cardiac abnormalities. Because of the • left-to-right shunt, hemodynamically significant lesions are accompanied by increased volume load on the right side of the heart • right atrial and ventricular dilation, right ventricular hypertrophy, and dilation of the pulmonary artery • Ostium primum • ASDs occur at the lowest part of the atrial septum • can 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 venosus • ASDs are located high in the atrial septum • often accompanied by anomalous drainage of the pulmonary veins into the right atrium or superior vena cava.

18. Clinical Features • ASDs • 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 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 the • prevention of complications, including heart failure, paradoxical embolization, and irreversible pulmonary vascular disease. • Mortality is low • postoperative 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.

19. VSDs • Incomplete closure of the ventricular septum allows left-to-right shunting • Most common congenital cardiac anomaly at birth • Normally formed by the fusion of; • an intraventricular muscular ridge that grows upward from the apex of the heart with • a thinner membranous partition that grows downward from the endocardial cushion. • The basal (membranous) region is the site of approximately 90% of VSDs • last part of the septum to develop • Overall incidence in adults is lower than that of ASDs • more common at birth than ASDs, • most VSDs close spontaneously in childhood, • Commonly associated with other cardiac malformations • Roughly 30% of VSDs occur in isolation

22. Morphology • Size and location of VSDs 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 • The diameter of the pulmonary artery is increased; • increased volume ejected by the right ventricle. • Vascular changes typical of pulmonary hypertension are common

23. Clinical Features • Small VSDs; • may be asymptomatic • those 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 correction • Small- or medium-sized defects; • produce jet lesions in the right ventricle • prone to superimposed infective endocarditis.

24. Patent ductus arteriosus • During intrauterine life; • blood flow from the pulmonary artery to the aorta • bypassing the unoxygenated lungs • Shortly after birth; the ductus constricts in response to; • increased arterial oxygenation, • decreased pulmonary vascular resistance, and • declining local levels of prostaglandin E2. • In healthy term infants • functionally 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 hypoxia • resulting from respiratory distress or heart disease • PDAs account for about 7% of cases of congenital heart lesions; • 90% are isolated defects • remaining occur with other congenital defects, most commonly VSDs.

27. Morphology • The 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 dilated • In PDAs some of the oxygenated blood flowing out from the left ventricle is shunted back to the lungs • resultant volume overload • Right heart hypertrophy and dilation. • With the development of pulmonary hypertension, • atherosclerosis of the main pulmonary arteries and proliferative changes in more distal pulmonary vessels

28. Clinical Features • PDAs; • high-pressure left-to-right shunts, • audible as harsh "machinery-like" murmurs. • A small PDA - no symptoms • larger bore defects - lead to the Eisenmenger syndrome with cyanosis and CHF. • The high-pressure shunt also predisposes affected individuals to infective endocarditis • There is general agreement that isolated PDAs should be closed as early in life as is feasible, • Preservation of ductal patency • by administering prostaglandin E • critically important for infants with various forms of congenital heart disease wherein the • PDA 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.

29. Right-to-Left Shunts • Cardiac malformations associated with right-to-left shunts are distinguished by • cyanosis 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 Fallot • transposition of the great vessels (Fig.) • Clinical findings associated with severe, long-standing cyanosis; • clubbing of the fingertips (hypertrophic osteoarthropathy) and polycythemia • In addition, right-to-left shunts permit venous emboli to bypass the lungs and directly enter the systemic circulation • paradoxical embolism

30. Tetralogy of Fallot • 5% of all congenital cardiac malformations, tetralogy of Fallot • most common cause of cyanotic congenital heart disease • The 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 hypertrophy • All of the features result from anterosuperior displacement of the infundibular septum, so that there is • abnormal division into the pulmonary trunk and aortic root. • Even untreated, some tetralogy patients can survive into adult life • Clinical severity largely depends on the degree of the pulmonary outflow obstruction.

33. Morphology • The 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 VSD • The pulmonary outflow tract is narrowed, and, in a few cases, the pulmonic valve may be stenotic • Additional abnormalities are present in many cases, including PDA or ASD; • actually beneficial in many respects, because they permit pulmonary blood flow.

34. Clinical Features • The 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 shunting • consequent 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.

35. Transposition of the Great Arteries • Discordant connection of the ventricles to their vascular outflow • The 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 (Fig.) • The atrium-to-ventricle connections are normal (concordant) • right atrium joining right ventricle and • left atrium emptying into left ventricle.

37. The functional outcome; • separation of the systemic and pulmonary circulations • a condition incompatible with postnatal life • shunt exists for adequate mixing of blood and delivery of oxygenated blood to the aorta. • stable shunt (35%) • Patients with TGA and a VSD • unstable shunts (65%) • Patients with only a patent foramen ovale or PDA • can close and often require surgical intervention within the first few days of life.

38. Morphology • TGA has many variants; • abnormal origin of the pulmonary trunk and aortic root • patients surviving beyond the neonatal period; • Varying combinations of ASD, VSD, and PDA • Right ventricular hypertrophy; • functions as the systemic ventricle • Left ventricle becomes somewhat atrophic; • support the low-resistance pulmonary circulation

39. Clinical Features • Early cyanosis • predominant manifestation of TGA • The outlook for neonates with TGA depends on; • the degree of the shunting • the magnitude of the tissue hypoxia • the ability of the right ventricle to maintain systemic pressures. • Procedures that enhance arterial oxygen saturation; • Infusions of prostaglandin E2 • maintain patency of the ductus arteriosus • Atrial septostomy • create ASDs • Even 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.

40. Congenital 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 chamber • subpulmonic stenosis in tetralogy of Fallot. • Relatively common examples of congenital obstruction include; • pulmonic valve stenosis, • aortic valve stenosis or atresia • coarctation of the aorta.

41. Aortic 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 coarctation • Two 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 defect • more 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.

43. Morphology • Preductal ("infantile") 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. • Because 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 blood flow. • Postductal ("adult") coarctation; • more common • sharply constricted by a ridge of tissue at or just distal to the ligamentum arteriosum • made 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 atherosclerotic • left ventricle is hypertrophic.

44. Clinical Features • depend 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 coarctation • cause 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 intervention • Postductal coarctation of the aorta without a PDA; • usually asymptomatic, and the disease may go unrecognized until well into adult life • upper 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.

45. SUMMARY • 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 shunts • most common and typically involve • ASDs, VSDs, or a PDA. These lesions • result 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 shunts • tetralogy of Fallot or transposition of great vessels • cyanotic lesions from the outset and are associated with polycythemia, hypertrophic osteoarthropathy, and paradoxical emboli. • Obstructive lesions include aortic coarctation; the • clinical severity of the lesion depends the degree of stenosis and the patency of the ductus arteriosus.

46. Congenital Heart Disease A general term to describe abnormalities of the heart or great vessels that are present from birth.

47. Congenital Heart Disease Three major categories: • left-to-right shunt (Acyanotic heart disease) • right-to-left shunt (Cyanotic heart disease) • obstruction (Stenosis / Atresia)

48. Acyanotic Heart Disease • Atrial Septal Defect (ASD), • Ventricular Septal Defect (VSD), • Patent Ductus Arteriosus (PDA), and • Atrioventricular Septal Defect (AVSD).

49. Ventricular Septal Defect (VSD)

50. Atrial Septal Defect (ASD)