Lilly Chapter 16: Congenital Heart Disease

ASD Physical Exam LOWER LEFT STERNAL BORDER. RV heave (dilated RV contraction) S2 widened, fixed (normal respiratory variation in systemic venous return is countered by reciprocal changes in volume of blood shunted across ASD) Systolic murmur at UPPER LEFT sternal border (increased blood flow across pulmonary valve) Perhaps a Mid-diastolic murmur at LOWER LEFT sternal border (increased flow across tricuspid valve) No murmur from blood through ASD itself (no significant pressure gradient between atria.

A prominent systolic impulse may be palpated along the lower-left sternal border, representing contraction of the dilated RV (termed an RV heave). The second heart sound (S2) demonstrates a widened, fixed splitting pattern (see Chapter 2). This occurs because the normal respiratory variation in systemic venous return is countered by reciprocal changes in the volume of blood shunted across the ASD. In addition, the increased volume of blood flowing across the pulmonary valve often creates a systolic murmur at the upper-left sternal border. A mid-diastolic murmur may also be present at the lower-left sternal border owing to the increased flow across the tricuspid valve. Blood traversing the ASD itself does not produce a murmur because of the absence of a significant pressure gradient between the atria.

2. VSD LEFT TO RIGHT SHUNT from LV to RV MEMBRANOUS portion>>> muscular portion of septum. Rarely, just below aortic valve or adjacent to AV valves.

A ventricular septal defect (VSD) is an abnormal opening in the interventricular septum (Fig. 16-12). VSDs are relatively common, having an incidence of 1.5 to 3.5 per 1,000 live births. They are most often located in the membranous (70%) and muscular (20%) portions of the septum. Rare VSDs occur just below the aortic valve or adjacent to the AV valves.

2. Atrioventricular Valve Development (M + T) FIG 16-9 After endocardial cushions fuse to form septa between R and L AV canals, 1. surrounding subendocardial mesenchymal tissue proliferates, and develops outgrowths similar to those of semilunar valves. 2. Sculpted by PROGRAMMED CELL DEATH (occurs within the inferior surface of nascent leaflets and in the ventricular wall). 3. Leaves behind only a few strands that connect valves to ventricular wall- superior portions degenerate, replaced by strings of dense CT- chordae tendinae.

After the endocardial cushions fuse to form the septa between the right and left AV canals, the surrounding subendocardial mesenchymal tissue proliferates and develops outgrowths similar to those of the semilunar valves. These are also sculpted by programmed cell death that occurs within the inferior surface of the nascent leaflets and in the ventricular wall. This process leaves behind only a few fine muscular strands to connect the valves to the ventricular wall (Fig. 16-9). The superior portions of these strands eventually degenerate and are replaced by strings of dense connective tissue, becoming the chordae tendineae.

Down Syndrome ASDs, VSDs, and PDAs Common AV canal-large primum ASD and VSD and undivided AV valve. Formed by abnormal migration patterns of endocardial cushions and neural crest cells.

Among infants with Down syndrome (trisomy 21), the incidence of congenital heart defects is nearly 40%. Many of these are common abnormalities such as ASDs, VSDs, and PDAs. There is also a high incidence of a rarer condition known as common AV canal, which consists of a large primum ASD and VSD and a common (undivided) AV valve. These central heart structures are usually formed by the ENDOCARDIAL CUSHIONS and cells of NEURAL CREST origin, which are known to have abnormal migration patterns in patients with trisomy 21.

1. ASD a. most common site: Foramen ovale, termed "ostium secundum ASD" causes: inadequate formation of septum secundum, excessive resorption of septum primum, or a combination. b. Less common site: inferior portion of intertribal septum, adjacent to AV valve, termed "ostium PRIMUM" defect. results from failure of SEPTUM PRIMUM to fuse with ENDOCARDIAL CUSHIONS. c. sinus venosus defect closely related to ASDs, morphologically distinct. called an "unroofing defect". No normal tissue between right pulmonary veins and right atrium, but technically not a deficiency of anatomic atrial septum (which is usually intact) d. related. 20% of population has PATENT FORAMEN OVALE. not a true ASD because no tissue is missing. PERSISTENCE OF FETAL ANATOMY, fusion fails to occur. Clinically silent because one way valve is functionally closed because of pressure gradient. If RA pressure becomes elevated (pulmonary HTN, R heart failure), or paradoxical embolism. If an embolism travels through PFO from systemic circulation into RA (AND RA PRESSURES ELEVATED due to valsalva, cough, pulmonary hypertension, sneeze, then EMBOLUS CAN TRANSFER INTO LEFT HEART and cause SYSTEMIC DAMAGE.

An atrial septal defect (ASD) is a persistent opening in the interatrial septum after birth that allows direct communication between the left and right atria. ASDs are relatively common, occurring with an incidence of 1 in 1,500 live births. They can occur anywhere along the atrial septum, but the most common site is at the region of the foramen ovale, termed an ostium secundum ASD (Fig. 16-11). This defect arises from inadequate formation of the septum secundum, excessive resorption of the septum primum, or a combination. Less commonly, an ASD appears in the inferior portion of the interatrial septum, adjacent to the AV valves. Named as ostium primum defect, this abnormality results from the failure of the septum primum to fuse with the endocardial cushions. A third type of atrial septal abnormality is termed a sinus venosus defect and is closely related to ASDs but is morphologically distinct. This condition represents an "unroofing" defect with absence of normal tissue between the right pulmonary vein(s) and the right atrium but is technically not a deficiency of the anatomic atrial septum (i.e., frequently the atrial septum itself is fully intact). As sinus venosus defects are often large and result in flow from the right pulmonary veins and left atrium into the right atrium, the pathophysiology is similar to that of a true ASD. Another distinct condition related to ASDs is patent foramen ovale, which is present in approximately 20% of the general population. It too is not a true ASD (i.e., no atrial septal tissue is "missing") but represents persistence of normal fetal anatomy. As described earlier, the foramen ovale typically functionally closes in the days after birth, and it is permanently sealed by the age of 6 months through fusion of the atrial septa. A PFO remains when this fusion fails to occur. A PFO is usually clinically silent because the one-way valve, though not sealed, remains functionally closed since the left atrial pressure is higher than that in the right atrium. However, a PFO takes on significance if the right atrial pressure becomes elevated (e.g., in states of pulmonary hypertension or right-heart failure), resulting in pathologic right-to-left intracardiac shunting. In that case, deoxygenated blood passes directly into the arterial circulation. Occasionally, a PFO can be implicated in a patient who has suffered a systemic embolism (e.g., a stroke). This situation, termed paradoxical embolism, occurs when thrombus in a systemic vein breaks loose, travels to the right atrium, then passes across the PFO to the left atrium if right-heart pressures are elevated, at least transiently (e.g., during a cough, sneeze, or Valsalva type maneuver), and then into the systemic arterial circulation.

PDA Pathophysiology Normal closure: Smooth muscle of ductus arteriosus usually constricts after birth, because of SUDDEN RISE IN BLOOD OXYGEN TENSION and REDUCTION in level of CIRCULATING PROSTAGLANDINS. Then, intimal proliferation and fibrosis keep it closed. Failed closure: persistent descending aorta and left pulmonary artery shunt. Before birth: pulmonary vascular resistance high, blood diverted away from immature lungs to aorta. Pulmonary resistance drops after birth, shunt reverses direction, and blood flows from AORTA to PULMONARY ARTERY. LEFT TO RIGHT SHUNT. CAUSES: pulmonary circulation, LA, LV become volume overloaded. LV dilation, L sided heart failure. Right heart stays normal unless pulmonary vascular disease ensues. If Eisenmenger syndrome occurs (ie pulmonary vascular disease does ensue), then shunt reverses again, with blood flowing from pulmonary artery to aorta. DESATURATED BLOOD sent to circulation, so cyanosis in LOWER EXTREMITIES. UPPER EXTREMITIES ARE FINE BECAUSE THEY RECEIVE BLOOD form PROXIMAL to ductus.

As described earlier, the smooth muscle of the ductus arteriosus usually constricts after birth owing to the sudden rise in blood oxygen tension and a reduction in the level of circulating prostaglandins. Over the next several weeks, intimal proliferation and fibrosis result in permanent closure. Failure of the ductus to close results in a persistent shunt between the descending aorta and the left pulmonary artery. The magnitude of flow through the shunt depends on the cross-sectional area and length of the ductus itself as well as the relative resistances of the systemic and pulmonary vasculatures. Prenatally, when the pulmonary vascular resistance is high, blood is diverted away from the immature lungs to the aorta. As the pulmonary resistance drops postnatally, the shunt reverses direction, and blood flows from the aorta into the pulmonary circulation instead. Because of this left-to-right shunt, the pulmonary circulation, left atrium, and LV become volume overloaded. This can lead to left ventricular dilatation and left-sided heart failure, whereas the right heart remains normal unless pulmonary vascular disease ensues. If the latter does develop, Eisenmenger syndrome results, with reversal of the shunt causing blood to flow from the pulmonary artery, through the ductus, to the descending aorta. In this case, the resulting flow of desaturated blood to the lower extremities causes cyanosis of the feet; the upper extremities are not cyanotic, because they receive normally saturated blood from the aorta proximal to the ductus.

B. Formation of the Heart Loop FIG 16-3 Constrictions/Dilations develop, the first signs of the primitive heart chambers. trunks arterioles (becomes aorta, pulmonary artery) , the bulbs cords (outlet of ventricles), the primitive ventricle (Inlet of Ventricles), the primitive atrium (R and L Atria), and the sinus venosus (part of right atrium) By day 23, continued growth and elongation in confined pericardial cavity force tube to bend on itself, formed a u-shaped loop on itself with Round end pointing ventrally and to the Right by day 28. RESULT: Atrium and Sinus Venous ABOVE AND BEHIND truncus arteriosus, bulbous cordis, and ventricle. No septa or valves yet. AV canal between primitive atrium and ventricle. AV canal becomes two separate canals: tricuspid and mitral valve. SINUS VENOUS eventually incorporated into RIGHT ATRIUM, forming both CORONARY SINUS and a portion of R Atrial Wall. BULBUS CORDIS and TRUNCUS ARTERIOLES contribute to future ventricular outflow tracts (proximal aorta and pulmonary artery)

As the tubular heart grows and elongates, it develops a series of alternate constrictions and dilations, creating the first sign of the primitive heart chambers—the truncus arteriosus, the bulbus cordis, the primitive ventricle, the primitive atrium, and the sinus venosus (Fig. 16-2). Continued growth and elongation within the confined pericardial cavity force the heart tube to bend on itself on day 23, eventually forming a U-shaped loop with the round end pointing ventrally and to the right by day 28. The result of this looping is placement of the atrium and sinus venosus above and behind the truncus arteriosus, bulbus cordis, and ventricle (Fig. 16-3). At this point, neither definitive septa between the developing chambers nor definitive valvular tissue have formed. The connection between the primitive atrium and ventricle is termed the atrioventricular (AV) canal. In time, the AV canal becomes two separate canals, one housing the tricuspid valve and the other the mitral valve. The sinus venosus is eventually incorporated into the right atrium, forming both the coronary sinus and a portion of the right atrial wall. The bulbus cordis and truncus arteriosus contribute to the future ventricular outflow tracts, forming parts of the proximal aorta and pulmonary artery.

2. Septation of the Ventricles and the Ventricular Outflow Tracts (two arterial channels-pulmonary artery and aorta, divided by aorticopulmonary septum). FIG 16-8 1. End of week 4: Primitive ventricle begins to grow. Leaves median muscular ridge, the primitive IV septum. 2. Early increase in height of septum results from DILATION OF the TWO NEW VENTRICLES FORMING ON EITHER SIDE OF IT. Only LATER does NEW cell growth contribute to septum size. 3. Free edge of muscular IV septum does NOT FUSE with endocardial cushions. Opening Interventricular Foramen remains open, communication allowed between RV and LV. Open UNTIL 7th week of gestation. 4. 7th WEEK: R and L bulbar ridges and ENDOCARDIAL CUSHIONS FORMS MEMBRANOUS PORTION of IV septum. 5. During week 5: Neural crest derived mesenchymal cells occurring in the BULBUS CORDIS and TRUNCUS ARTErIOSUS create BULBAR RIDGES (pair of protrusions). These ridges fuse in midland, spiral 180 degrees, form AorticoPulmonary Septum, dividing BULBIS CORDIS and TRUNCUS ARTERIOSUS into TWO ARTERIAL CHANNELS (pulmonary artery and aorta).

At the end of the 4th week, the primitive ventricle begins to grow, leaving a median muscular ridge, the primitive interventricular septum. Most of the early increase in height of the septum results from dilation of the two new ventricles forming on either side of it. Only later does new cell growth in the septum itself contribute to its size. The free edge of the muscular interventricular septum does not fuse with the endocardial cushions; the opening that remains and allows communication between the right ventricle (RV) and left ventricle (LV) is the interventricular foramen (Fig. 16-7). This remains open until the end of the 7th week of gestation, when the fusion of tissue from the right and left bulbar ridges and the endocardial cushions forms the membranous portion of the interventricular septum. During the 5th week, neural crest-derived mesenchymal proliferation occurring in the bulbus cordis and truncus arteriosus creates a pair of protrusions known as the bulbar ridges (Fig. 16-8). These ridges fuse in the midline and undergo a 180-degree spiraling process, forming the aorticopulmonary septum. This septum divides the bulbus cordis and the truncus arteriosus into two arterial channels, the pulmonary artery and the aorta, the former continuous with the RV and the latter with the LV.

AS Physical Examination HARSH CRESCENDO DECRESCENDO MURMUR at BASE OF HEART (up near aortic region ie R 2nd ICS) Often preceded by ejection click, especially with a bicuspid vale. Present from birth, *UNLIKE ASD, VSD, PDA. Does not depend on decline of pulmonary vascular resistance. severe diseasE: LONGER murmur, peaks later in systole. paradoxical split of S2 (A2 preceeds P2)

Auscultation reveals a harsh crescendo-decrescendo systolic murmur, loudest at the base of the heart with radiation toward the neck. It is often preceded by a systolic ejection click (see Chapter 2), especially when a bicuspid valve is present. Unlike the murmurs of ASD, VSD, or PDA, the murmur of congenital AS is characteristically present from birth because it does not depend on the postnatal decline in pulmonary vascular resistance. With advanced disease, the ejection time becomes longer, causing the peak of the murmur to occur later in systole. In severe disease, the significantly prolonged ejection time causes a delay in closure of the aortic valve such that A2 occurs after P2—a phenomenon known as reversed splitting (also termed "paradoxical splitting") of S2 (see Chapter 2).

CA Pathophysiology aortic narrowing in coarctation INCREASES LV AFTERLOAD. Blood flow to head and upper body OK because branch off aorta BEFORE OBSTRUCTION. Flow to descending aorta and lower body sometimes diminished. COMPENSATORY ALTERATIONS: 1. LVH 2. DILATATION OF COLLATERAL BLOOD VESSELS from INTERCOSTAL ARTERIES that bypass coarctation and provide blood to more distal descending aorta. Can ENLARGE SO MUCH THEY DAMAGE THE RIBS.

Because of the impedance of aortic narrowing in coarctation, the LV faces an increased afterload. Blood flow to the head and upper extremities is preserved because the vessels supplying these areas usually branch off the aorta proximal to the obstruction, but flow to the descending aorta and lower extremities may be diminished. If coarctation is not corrected, compensatory alterations include (1) development of left ventricular hypertrophy and (2) dilatation of collateral blood vessels from the intercostal arteries that bypass the coarctation and provide blood to the more distal descending aorta. Eventually, these collateral vessels enlarge and can erode the undersurface of the ribs

AS Pathophysiology Narrowed orifice. LV systolic pressure must rise above aorta's. causes LVH. High velocity sharp stream of blood from LV into aorta may damage aorta and contribute to dilatation.

Because the valvular orifice is significantly narrowed, left ventricular systolic pressure must increase to pump blood across the valve into the aorta. In response to this increased pressure load, the LV hypertrophies (Fig. 16-14). The high-velocity jet of blood that passes through the stenotic valve may impact the proximal aortic wall and contribute to dilatation of that vessel.

TofF Treatment CREATE anatomic communicaitons between aorta to pulmonary artery ( inducing a LEFT to RIGHT shunt, to increase pulmonary blood flow. ) Done in patients who will get a procedure when older. complete surgical correction: closure of VSD, enlargement of subpulmonary infundibulum by pericardial patch. 6-12 months recommended, decrease likelihood of future complications. Most who get repaired become normal adults. Antibiotic prophylaxis to prevent endocarditis is sometimes required in some.

Before definitive surgical correction of tetralogy of Fallot was developed, several forms of palliative therapy were undertaken. These involved creating anatomic communications between the aorta (or one of its major branches) to the pulmonary artery, establishing a left-to-right shunt to increase pulmonary blood flow. Such procedures are occasionally used today in infants for whom definitive repair is planned at an older age. Complete surgical correction of tetralogy of Fallot involves closure of the VSD and enlargement of the subpulmonary infundibulum with the use of a pericardial patch. Elective repair is usually recommended at 6 to 12 months of age to decrease the likelihood of future complications. Most patients who have undergone successful repair grow to become asymptomatic adults. However, antibiotic prophylaxis to prevent endocarditis is required in some patients (see Chapter 8).

VSD Treatment 50% by age 2 close spontaneously. with heart failure or PHTN: surgical repair. L to R shunt can correct later. Catheter based in selected patients.

By age 2, at least 50% of small and moderate-sized VSDs undergo sufficient partial or complete spontaneous closure to make intervention unnecessary. Surgical correction of the defect is recommended in the first few months of life for children with accompanying heart failure or pulmonary vascular hypertension. Moderate-sized defects without pulmonary vascular disease but with significant left-to-right shunting can be corrected later in childhood. Less-invasive catheter-based treatments are also used in selected patients.

II. Normal Development of the Cardiovascular System

By the 3rd week of gestation, the nutrient and gas exchange needs of the rapidly growing embryo can no longer be met by diffusion alone, and the tissues begin to rely on the developing cardiovascular system to deliver these substances over long distances.

CHARGE COLOBOMA (congenital absence of portions of eyes) Heart defects choanal atresia (nasal passage obstruction) Retardation of growth and development Genitoruinary malformation Ear abnormalities Autosomal DOMINANT disorder. Cardiac abnormalities including INTERRUPTED AORTIC ARCH TEETRALOGY of FALLOt Double outlet right ventricle AV septal defects. CHD7 gene deltion, protein product of which is transcription regulator associated with several tissue-specific target genes.

CHARGE syndrome (the acronym for coloboma [congenital absence of portions of eye structures], heart defects, choanal atresia [nasal passage obstruction], retardation of growth and development, genitourinary malformation, ear abnormalities) is an autosomal dominant disorder that includes some or all of the listed components. Associated cardiac abnormalities include interrupted aortic arch, tetralogy of Fallot, double outlet right ventricle, and AV septal defects. The incidence of the syndrome is approximately 1:10,000 children, and most are found to have a mutation or microdeletion in the CHD7 gene, the protein product of which is a transcription regulator associated with several tissue-specific target genes.

TofF Diagnostic Studies CxR: RV enlarged. DECREASED main pulmonary artery segment. BOOT SHAPED HEART. Pulmonary vascular markings DIMINISHED b/c decreased flow through pulmonary circulation. ECG: RVH, R axis deviation. Echo: RV outflow tract anatomy, malaligned VSD, RVH, associated defects, as does cardiac cath.

Chest radiography demonstrates prominence of the RV and decreased size of the main pulmonary artery segment, giving the appearance of a "boot-shaped" heart. Pulmonary vascular markings are typically diminished because of decreased flow through the pulmonary circulation. The ECG shows right ventricular hypertrophy with right axis deviation. Echocardiography details the right ventricular outflow tract anatomy, the malaligned VSD, right ventricular hypertrophy, and other associated defects, as does cardiac catheterization.

Eisenmenger Syndrome Diagnostic Studies CXR: Proximal pulmonary artery dilatation, peripheral tapering. Calcification of pulmonary vasculature. ECG: RVH, RA Enlargement. Echo with doppler: underlying cardiac defect, quantitate pulmonary artery systolic pressure.

Chest radiography in Eisenmenger syndrome is notable for proximal pulmonary artery dilatation with peripheral tapering. Calcification of the pulmonary vasculature may be seen. The ECG demonstrates right ventricular hypertrophy and right atrial enlargement. Echocardiography with Doppler studies can usually identify the underlying cardiac defect and quantitate the pulmonary artery systolic pressure.

TGA Diagnostic Studies CXR: Heart base may be narrow (more anteiror posterior orientaiton of AORTA and PULMONARY ARTERY) ECG: RVH, (RV is systemic high pressure pump chamber) Echo: abnormal orientation of great vessels. Definitive.

Chest radiography is usually normal, although the base of the heart may be narrow owing to the more anterior-posterior orientation of the aorta and pulmonary artery. The ECG demonstrates right ventricular hypertrophy, reflecting the fact that the RV is the systemic "high-pressure" pumping chamber. The definitive diagnosis of transposition can be made by echocardiography, which demonstrates the abnormal orientation of the great vessels.

PS Symptoms mild/moderate: asymptomatic. severe: some dyspnea with exertion, exercise intolerance, symptoms of R heart failure (abdominal fullness, pedal edema)

Children with mild or moderate pulmonary stenosis are asymptomatic. The diagnosis is often first made on discovery of a murmur during a routine physical examination. Severe stenosis may cause manifestations such as dyspnea with exertion, exercise intolerance, and with decompensation, symptoms of right-sided heart failure such as abdominal fullness and pedal edema.

PDA Symptoms Asymptomatic. Large Left to Right shunts: Moderate lesions: AFIB- due to LA dilatation. Turbulent flow- endarteritis (infection)

Children with small PDAs are generally asymptomatic. Those with large left-to-right shunts develop early congestive heart failure with tachycardia, poor feeding, slow growth, and recurrent lower respiratory tract infections. Moderate-sized lesions can present with fatigue, dyspnea, and palpitations in adolescence and adult life. Atrial fibrillation may occur owing to left atrial dilatation. Turbulent blood flow across the defect can set the stage for endovascular infection, similar to endocarditis but more accurately termed endarteritis.

TofF Physical Examination PS outflow obstruction from RV = prognostic marker. TofF and moderate pulmonary stenosis: cyanosis of lips, mucus membranes, digits. Sever: profound cyanosis in first few days of life. Right to Left shunt chronic: clubbing fingers, toes. RVH- palpable HEAVE on LEFT STERNAL BORDER. S2 single of Aortic component. Pulmonary component dull and inaudible. EJECTION MURMUR SYSTOLIC at LEFT STERNAL BORDER caused by turbulent blood flow through stenotic RV outflow No DISTINCT VSD murmur, because SO LARGE

Children with tetralogy of Fallot and moderate pulmonary stenosis often have mild cyanosis, most notably of the lips, mucous membranes, and digits. Infants with severe pulmonary stenosis may present with profound cyanosis in the first few days of life. Chronic hypoxemia caused by the right-to-left shunt commonly results in clubbing of the fingers and toes. Right ventricular hypertrophy may be appreciated on physical examination as a palpable heave along the left sternal border. The S2 is single, composed of a normal aortic component; the pulmonary component is soft and usually inaudible. A systolic ejection murmur heard best at the upper left sternal border is created by turbulent blood flow through the stenotic right ventricular outflow tract. There is usually no distinct murmur related to the VSD, because it is typically large and thus generates little turbulence.

TofF Symptoms SPELLS following exertion, feeding, crying when systemic vasodilation results in INCREASED RIGHT TO LEFT SHUNT. SQUATTING INCREASES systemic vascular RESISTANCE by kinking femoral arteries, decreasing R to L shunt, directing more blood from RV to lungs (overcomming VSD and PS)

Children with tetralogy of Fallot often experience dyspnea on exertion. "Spells" may occur following exertion, feeding, or crying when systemic vasodilatation results in an increased right-to-left shunt. Manifestations of such spells include irritability, cyanosis, hyperventilation, and occasionally syncope or convulsions. Children learn to alleviate their symptoms by squatting down, which is thought to increase systemic vascular resistance by "kinking" the femoral arteries, thereby decreasing the right-to-left shunt and directing more blood from the RV to the lungs.

6. Coarctation of the Aorta discrete narrowing of aortic lumen. Commonly associated with bicuspid aortic valve. TURNER SYNDROME MOST are just next to the ductus arteriosus (juxtaductal) Possible causes: 1. Less forward flow through left side of heart and ascending aorta during fetal life leads to hypoplastic development of aorta (no flow no grow) 2. Ectopic muscular ductus arteriosus tissue extends into aorta during fetal life, constricts following birth at same time ductus closed. 3. One manifestation of more diffuse aortic disease.

Coarctation of the aorta typically consists of a discrete narrowing of the aortic lumen (Fig. 16-16). This anomaly has an incidence of 1 in 6,000 live births, and the most common associated cardiac abnormality is a bicuspid aortic valve. Aortic coarctation often occurs in patients with Turner syndrome (45, XO). In the past, coarctations were described as either "preductal" (infantile) or "postductal" (adult-type) based on the location of the aortic narrowing in relation to the ductus arteriosus. These terms have been largely abandoned because the vast majority of coarctations are actually juxtaductal (i.e., "next to" the ductus) and etiologic differences between the preductal and postductal categories have not been substantiated. While the actual pathogenesis of aortic coarctation has not been defined, one theory contends that reduced antegrade blood flow through the left side of the heart and ascending aorta during fetal life leads to hypoplastic development of the aorta ("no flow, no grow"). Another theory is that ectopic muscular ductus arteriosus tissue extends into the aorta during fetal life and constricts following birth at the same time the ductus is caused to close. More recent evidence suggests that aortic coarctation may be just one manifestation of a more diffuse aortic disease.

4. Congenital Aortic Stenosis Cause: abnormal structural development of valve leaflets. 20% have additional congenital heart defect. USUALLY A BICUSPID AORTIC VALVE, causing eccentric stenotic opening. MOST nonobstructive at birth, only rarely cause CONGENITAL AS. More often progressively stenotic over great many years, as leaflets progressively fibrose and calcify. A common cause of AS in adults.

Congenital aortic stenosis (AS) is most often caused by abnormal structural development of the valve leaflets. It occurs in 5 of 10,000 live births and is four times as common in males as in females. Twenty percent of patients have an additional abnormality, most commonly coarctation of the aorta (discussed later). The aortic valve in congenital AS usually has a bicuspid leaflet structure instead of the normal three-leaflet configuration, causing an eccentric stenotic opening through which blood is ejected. Most bicuspid aortic valves are actually nonobstructive at birth and therefore only rarely result in congenital AS. More often, bicuspid valves become progressively stenotic over a great many years, as the leaflets progressively fibrose and calcify, and represent a common cause of AS in adults (see Chapter 8).

IV. Common Congenital Heart Lesions Do not present before birth because shunt through ductus arteriosus and foramen ovale, bypassing most defects. Cyanotic: : RIGHT to LEFT shunts (bypass lungs) Blue purple discolored skin and mucus membranes. Elevated deoxyHb, with 80-85% O2 sat. Cyanotic: LEFT TO RIGHT shunts ( stenoses, regurgitation, etc. ) Eisenmanger syndrome: LEFT TO RIGHT shunt, large, over time, cause PULMONARY ARTERY VOL and PRESSURE TO INCREASE, can be associated with later pulmonary arteriolar HYPERTROPHY and resistance to flow..... causing original direction of shunt to REVERSE...RIGHT TO LEFT supervenes, causing hypoxemia and cyanosis. Congenital Heart Diseases also subject to increased risk of infective endocarditis

Congenital heart defects are generally well tolerated before birth. The fetus benefits from shunting of blood through the ductus arteriosus and the foramen ovale, allowing the bypass of most defects. It is only after birth, when the neonate has been separated from the maternal circulation and the oxygenation it provides, and the fetal shunts have closed, that congenital heart defects usually become manifest. Congenital heart lesions can be categorized as cyanotic or acyanotic. Cyanosis refers to a blue-purple discoloration of the skin and mucous membranes caused by an elevated blood concentration of deoxygenated hemoglobin (usually >4 g/dL, which corresponds to an arterial O2 saturation of approximately 80% to 85% in a neonate with a normal total hemoglobin level). In congenital heart disease, cyanosis results from defects that allow poorly oxygenated blood from the right side of the heart to be shunted to the left side, bypassing the lungs. Acyanotic lesions include intracardiac or vascular stenoses, valvular regurgitation, and defects that result in left-to-right shunting of blood. Large left-to-right shunts at the atrial, ventricular, or great vessel level (all described in the following sections) cause the pulmonary artery volume and pressure to increase and can be associated with the later development of pulmonary arteriolar hypertrophy and subsequently increased resistance to flow. Over time, the elevated pulmonary resistance may force the direction of the original shunt to reverse, causing right-to-left flow to supervene, accompanied by the physical findings of hypoxemia and cyanosis. The development of pulmonary vascular disease as a result of a chronic large left-to-right shunt is known as Eisenmenger syndrome and is described later in the chapter. Patients with congenital heart disease are susceptible to infective endocarditis. Chapter 8 describes the pathophysiology of endocarditis and summarizes the appropriate selection of patients for antibiotic prophylaxis prior to procedures that can result in bacteremia.

I. Introduction Most common form of birth defects, most common cause of death from birth defects in first year of life. Mild defects may escape detection for weeks, months, or years. Genetic mutations, environmental factors, maternal illness, ingestion of toxins during pregnancy can contribute to cardiac malformations. Formation of CV system starts in week 3.

Congenital heart diseases are the most common form of birth defects and are the leading cause of death from birth abnormalities in the first year of life. These conditions affect approximately 8 of 1,000 live births, and an estimated 1 million people in the United States have congenital heart lesions. Some abnormalities are severe and require immediate medical attention, whereas many are less pronounced and have minimal clinical consequences. Although congenital heart defects are present at birth, milder defects may remain inapparent for weeks, months, or years and may even escape detection until adulthood. The past half-century has witnessed tremendous advances in the understanding of the pathophysiology of congenital heart diseases and substantial improvements in the ability to evaluate and treat those afflicted. Research has shown that genetic mutations, environmental factors, maternal illness, or ingestion of toxins during pregnancy can contribute to cardiac malformations. However, specific etiologies remain unknown in most cases. The survival of children with congenital heart disease has also improved dramatically in recent decades, largely because of better diagnostic and interventional techniques. However, the lifelong needs of affected patients include guidance regarding physical activity, pregnancy, and employment. Formation of the cardiovascular system begins during the 3rd week of embryonic development. Soon after, a unique circulation develops that allows the fetus to mature in the uterus, using the placenta as the primary organ of gas, nutrient, and waste exchange. At birth, the fetal lungs inflate and become functional, making the placenta unnecessary and dramatically altering circulation patterns to allow the neonate to adjust to life outside the womb. Given the remarkable complexity of these processes, it is easy to envision ways that cardiovascular malfunctions could develop. This chapter begins with an overview of fetal cardiovascular development and then describes the most common forms of congenital heart disease.

DiGeorge Syndrome PHARYNGEAL defects hyPOcalcemia due to absent PARATHYROID GLANDs T cell dysfunction secondary to HYPOPLASIA OF THYMUS Cardia coutlfow tract ABNORMALITIES: TETRALLOGY OF FALLOt TRUNCUS ARTRERIOSUS (large VSD) interrupted aortic arch. MICRODELETION IN CHROMOME 22: 22q11. TBX1 gene is in this region. developmental patterning of cardiac outflow tracts.

DiGeorge syndrome (characterized by pharyngeal defects, hypocalcemia due to absent parathyroid glands, and T-cell dysfunction secondary to hypoplasia of the thymus) is associated with congenital abnormalities of the cardiac outflow tracts, including tetralogy of Fallot, truncus arteriosus (a large VSD over which a single large outflow vessel arises), and interrupted aortic arch. Most patients with DiGeorge syndrome have a microdeletion within chromosome 22 (22q11), a region that contains the TBX1 gene. This gene encodes a transcription factor that appears to play a critical role in developmental patterning of the cardiac outflow tracts.

V. Eisenmenger Syndrome Severe pulmonary obstruction results FROM CHRONIC LEFT TO RIGHT SHUNTING through a congenital defect (acyanotics) Elevated pulmonary vascular resistance causes reversal of original shunt ( TO RIGHT TO LEFT) and systemic cyanosis.

Eisenmenger syndrome is the condition of severe pulmonary vascular obstruction that results from chronic left-to-right shunting through a congenital cardiac defect. The elevated pulmonary vascular resistance causes reversal of the original shunt (to the right-to-left direction) and systemic cyanosis.

Summary

Formation of the cardiovascular system begins during the 3rd week of embryonic development; soon after, a unique circulation develops that allows the fetus to mature in the uterus, using the placenta as the primary organ of gas, nutrient, and waste exchange. At birth, the fetal lungs inflate and become functional, making the placenta unnecessary and altering circulation patterns to allow the neonate to adjust to life outside the womb. Cardiac malformations occur in 0.8% of live births, representing the most common form of birth defects and the leading cause of death from birth abnormalities in the first year of life. Congenital heart lesions can be grouped into cyanotic or acyanotic defects, depending on whether the abnormality results in right-to-left shunting of blood. Acyanotic defects often result in either volume overload (ASD, VSD, PDA) or pressure overload (AS, pulmonic stenosis, coarctation of the aorta). Chronic volume overload resulting from a large left-to-right shunt can ultimately result in increased pulmonary vascular resistance, reversal of the direction of shunt flow, and subsequent cyanosis (Eisenmenger syndrome). Among the most common cyanotic defects are tetralogy of Fallot and transposition of the great arteries.

1. Septation of the AV Canal Fig 16-6 Endocardial cushion growth contributes to ATRIAL SEPTATION. (also contributes to IV septum) Endocardial cushions begin as gelatinous CT layer swellings WITHIN AV CANAL. Migrating cells from primitive ENDOCARDIUM move into them, and transform into MESENCHYMAL CELLS. This tissue grows on HORIZONTAL PLANE, resulting in septation of AV canal through continued growth of lateral, superior, inferior endocardial cushions, closing off all but 2 canals: L and R AV canals that later become tricuspid and mitral orifices later.

Growth of the endocardial cushions contributes to atrial septation and, as described later, to the membranous portion of the interventricular septum. Endocardial cushions initially begin as swellings of the gelatinous connective tissue layer within the AV canal. They are then populated by migrating cells from the primitive endocardium and subsequently transform into mesenchymal tissue. Tissue growth occurs primarily in the horizontal plane, resulting in septation of the AV canal through the continued growth of the lateral, superior, and inferior endocardial cushions (Fig. 16-6). Septation creates the right and left canals that later give rise to the tricuspid and mitral orifices, respectively.

B. Transitional Circulation Ductus venous, foramen ovale, ductus arteriosus are all supposed to close. 1. UMBILICAL CORD IS CLAMPED: low resistance placental flow removed from ARTERIAL SYSTEM, causing INCREASE IN SYSTEMIC VASCULAR RESISTANCE. 2. At the same time, pulmonary vascular resistance falls for 2 reasons: a. mechanical inflation of lungs stretches tissues, causing pulmonary artery expansion and wall thinning b. vasodilation of pulmonary vasculature occurs in response to rise in blood oxygen tension accompanying aeration of lungs. 3. reduced pulmonary resistance--------INCREASED PULMONARY BLOOD FLOW. most pronounced in first day, continues for several weeks. 4. Pulmonary resistance falls and more blood travels to lungs through pulmonary artery, VENOUS RETURN FROM PULMONARY VEINS to LEFT ATRIUM also increases, causing LEFT ATRIAL PRESSURE to rise. 5. Also, umbilical venous flow (INTO FETUS) has stopped, and constriction of ductus venous occurs. BOTH CAUSE FALL IN IVC and RIGHT ATRIAL PRESSURES. so... LEFT ATRIAL PRESSURE BECOMES GREATER THAN RIGHT ATRIAL PRESSURE, FORAMEN OVALE VALVE CLOSES, eliminating right to left shunt. the valve fuses with IA septum eventually. 6. oxygenation occurring in newborn lungs, ductus arteriosus closes as it is superfluous. In the womb, high PROSTAGLANDIN E1 in response to HYPOXIA is present at birth, vasodilation keeps ductus arteriosus open. PGE1 levels decline after birth, o2 tension rises, ductus constricts (hours to days). Failure to constrict (low responsively to vasoactive substances) more common in premature infants. PDA Anatomic separation of circulatory paths of R and L sides of heart complete. LV increases SV RV decreases SV, equalizing CO from both. LV higher pressure, hypertrophies.

Immediately following birth, the neonate rapidly adjusts to life outside the womb. The newly functioning lungs replace the placenta as the organ of gas exchange, and the three shunts (ductus venosus, foramen ovale, and ductus arteriosus) that operated during gestation ultimately close. This shift in the site of gas exchange and the resulting changes in cardiovascular architecture allow the newborn to survive independently. As the umbilical cord is clamped or constricts naturally, the low-resistance placental flow is removed from the arterial system, resulting in an increase in systemic vascular resistance. Simultaneously, pulmonary vascular resistance falls for two reasons: (1) the mechanical inflation of the lungs after birth stretches the lung tissues, causing pulmonary artery expansion and wall thinning, and (2) vasodilatation of the pulmonary vasculature occurs in response to the rise in blood oxygen tension accompanying aeration of the lungs. This reduction in pulmonary resistance results in a dramatic rise in pulmonary blood flow. It is most marked within the first day after birth but continues for the next several weeks until adult levels of pulmonary resistance are achieved. As pulmonary resistance falls and more blood travels to the lungs through the pulmonary artery, venous return from the pulmonary veins to the left atrium also increases, causing left atrial pressure to rise. At the same time, cessation of umbilical venous flow and constriction of the ductus venosus cause a fall in IVC and right atrial pressures. As a result, the left atrial pressure becomes greater than that in the right atrium, and the valve of the foramen ovale is forced against the septum secundum, eliminating the previous flow between the atria (see Fig. 16-5). Failure of the valve to permanently fuse to the septum secundum results in a patent foramen ovale (PFO), as described later in this chapter. With oxygenation now occurring in the newborn lungs, the ductus arteriosus becomes superfluous and closes. During fetal life, a high circulating level of prostaglandin E1 (PGE1) is generated in response to relative hypoxia, which causes the smooth muscle of the ductus arteriosus to relax, keeping it patent. After birth, PGE1 levels decline as the oxygen tension rises and the ductus therefore constricts. In a healthy full-term infant, this occurs during the first hours to days after delivery. The responsiveness of the ductus to vasoactive substances depends on the gestational age of the fetus, and it often fails to constrict in premature infants. This results in the congenital anomaly known as patent ductus arteriosus (PDA) (described below). With the anatomic separation of the circulatory paths of the right and left sides of the heart now complete, the stroke volume of the LV increases and that of the RV decreases, equalizing the cardiac output from both ventricles. The augmented pressure and volume load placed on the LV induces the myocardial cells of that chamber to hypertrophy, while the decreased pressure and volume loads on the RV result in gradual regression of RV wall thickness.

CA Diagnostic Studies CXR: NOTCHING of interior surface of posterior ribs because of COLLATERAL INTERCOSTAL CIRCULATION. An indented aorta at site of coarctation. ECG: LVH because pressure overload. Doppler echo: coarctation, assess pressure gradient across lesion. MR or CT: demonstrates length and severity of coarctation.

In adults with uncorrected coarctation of the aorta, chest radiography generally reveals notching of the inferior surface of the posterior ribs owing to enlarged intercostal vessels supplying collateral circulation to the descending aorta. An indented aorta at the site of coarctation may also be visualized. The ECG shows left ventricular hypertrophy resulting from the pressure load placed on that chamber. Doppler echocardiography confirms the diagnosis of coarctation and assesses the pressure gradient across the lesion. Magnetic resonance (or CT) imaging demonstrates in detail the length and severity of coarctation (see Fig. 16-17). Diagnostic catheterization and angiography are rarely necessary.

Williams Syndrome Mental retardation hyrPERcalcemia Renovascular hypertension facial abnormalities short stature SUPRAVALVULAR AS DIFFUSE ARTERIOPATHY OF AORTA and PULMONARY ARTERY OBSTRUCTION. Chromosome 7 DELETION, region including elastin gene, critical in arterial wall.

In contrast, discrete gene abnormalities have been identified in other syndrome-associated forms of congenital heart disease. Many patients with Williams syndrome (characterized by mental retardation, hypercalcemia, renovascular hypertension, facial abnormalities, and short stature) have supravalvular AS, and some have a more diffuse arteriopathy of the aorta as well as pulmonary artery obstruction. The genetic abnormality in Williams syndrome is a deletion on chromosome 7 (7q11.23), a region that includes the elastin gene. Abnormalities in the production of elastin, a critical component of the arterial wall, may be responsible for the observed arteriopathy.

A. Fetal Circulation FIG 16-10 !!!!! Placenta- Umbilical Vein- 1/2: Ductus venous-(bypass liver)IVC 1/2: Portal vein and hepatic veins-IVC (IVC blood = mixture of well and de oxygenated blood. Higher oxygen in IVC stream to RA than in SVC stream to RA. These two streams are partially separated WITHIN THE RA, to allow: -MOST blood: high oxygen blood to go to heart and brain (from RA to LA via patent FORAMEN OVALE to LV to aortic arch proximal to ductus arteriosus. This portion of aorta remains high oxygen, sent upward), -and low oxygen blood to divert to placenta via descending aorta and umbilical arteries(via from RA to RV and into Pulmonary arteries through patent ductus arteriosus into DESCENDING AORTA 1. Passage of well oxygenated blood from Right to Left Atrium is facilitated by CRISTA DIVIDENS, the inferior border of the septum secundum, which overrides IVC opening into Right Atrium. 2. THIS SHUNTED blood mixes with small amounts of OXYGEN POOR blood returning through the LEFT ATRIUM from fetal pulmonary veins (lungs in utero consume oxygen). 3. LA to LV 4. Pumped out of aortic valve into ascending aorta. Well oxygenated blood distributed to (9%) coronary arteries, (62%) carotid/subclavian to upper body and brain, (29%) descending aorta and fetal body (mixed with venous blood from patent ductus arteriosus. Remaining WELl oxygenated IVC blood enters RA mixes with deoxygenated blood from SVC, passes to RV. RV IS WORK HOUSE IN FETUS. 2/3 of TOTAL CARDIAC OUTPUT. FLOWS INTO PULMONARY ARTERY and 1. into lungs or 2. through ductus arteriosus into descending aorta, mixing with LV well oxygenated blood. EFFICIENT. Lungs bypassed because fetal lungs incapable of gas exchange, fluid filled. ow oxygen tension of fluid causes constriction of pulmonary vessels. INCREases pulmonary vascular resistance, facilitates shunt through ductus arteriosus to systemic circulation. From descending aorta, blood distributed to lower body and umbilical arteries-back to placenta for gas exchange.

In fetal life, oxygenated blood leaves the placenta through the umbilical vein (Fig. 16-10). Approximately half of this blood is shunted through the fetal ductus venosus, bypassing the hepatic vasculature and proceeding directly into the inferior vena cava (IVC). The remaining blood passes through the portal vein to the liver and then into the IVC through the hepatic veins. IVC blood is therefore a mixture of well-oxygenated umbilical venous blood and the blood of low oxygen tension returning from the systemic veins of the fetus. Because of this mixture, the oxygen tension of inferior vena caval blood is higher than that of blood returning to the fetal right atrium from the superior vena cava. This distinction is important because these two streams of blood are partially separated within the right atrium to follow different circulatory paths. The consequence of this separation is that the fetal brain and myocardium receive blood of relatively higher oxygen content, whereas the more poorly oxygenated blood is diverted to the placenta (via the descending aorta and umbilical arteries) for subsequent oxygenation. Most IVC blood entering the right atrium is directed to the left atrium through the foramen ovale. This intracardiac shunt of relatively well-oxygenated blood is facilitated by the inferior border of the septum secundum, termed the crista dividens, which is positioned such that it overrides the opening of the IVC into the right atrium. This shunted blood then mixes with the small amount of poorly oxygenated blood returning to the left atrium through the fetal pulmonary veins (remember that the lungs are not ventilated in utero; the developing pulmonary tissues actually remove oxygen from the blood). From the left atrium, blood flows into the LV and is then pumped into the ascending aorta. This well-oxygenated blood is distributed primarily to three territories: (1) approximately 9% enters the coronary arteries and perfuses the myocardium, (2) 62% travels in the carotid and subclavian vessels to the upper body and brain, and (3) 29% passes into the descending aorta to the rest of the fetal body. The remaining well-oxygenated inferior vena caval blood entering the right atrium mixes with poorly oxygenated blood from the superior vena cava and passes to the RV. In the fetus, the RV is the actual "workhorse" of the heart, providing two thirds of the total cardiac output. This output flows into the pulmonary artery and from there either into the lungs (12% of RV output), or through the ductus arteriosus into the descending aorta (88% of RV output), where it mixes with the better oxygenated blood from the LV described in the previous paragraph. This unequal distribution of right ventricular outflow is actually quite efficient. Bypassing the lungs is desired because the fetal lungs are filled with amniotic fluid and are incapable of gas exchange. The low oxygen tension of this fluid causes constriction of the pulmonary vessels, which increases pulmonary vascular resistance and facilitates shunting of blood through the ductus arteriosus to the systemic circulation. From the descending aorta, blood is distributed to the lower body and to the umbilical arteries, leading back to the placenta for gas exchange.

AS Treatment Mild: follow. Severe: transcatheter balloon valvuloplasty = FIRST LINE. inflate and break calcifications. Surgical repair considered if it fails or causes regurgitation. Palliative only, must be repeated again

In its milder forms, congenital AS does not need to be corrected but should be followed closely as the degree of stenosis may worsen over time. Severe obstruction of the aortic valve during infancy may mandate immediate repair. Transcatheter balloon valvuloplasty is the first line of intervention, but surgical repair may be necessary if valvuloplasty fails to relieve the obstruction or if significant aortic regurgitation results from balloon dilation. Often, valvuloplasty in infancy is only palliative, and repeat catheter balloon dilation or surgical revision is needed later.

CA Treatment PGE infusion to keep DA patent, maintaining blood flow to descending aorta before surgery is undertaken. elective repair in children to prevent HTN: excision of narrowed segment and end to end re-enneastemosis . or direct repair using synthetic patch. Older children, adults, trans catheter, balloon dilatation with or without stent is successful.

In neonates with severe obstruction, prostaglandin infusion is administered to keep the ductus arteriosus patent, thus maintaining blood flow to the descending aorta before surgery is undertaken. In children, elective repair is usually performed to prevent systemic hypertension. Several effective surgical procedures are available, including excision of the narrowed aortic segment with end-to-end reanastomosis and direct repair of the coarctation, sometimes using synthetic patch material. For older children, adults, and patients with recurrent coarctation after previous repair, transcatheter interventions (balloon dilatation with or without stent placement) are usually successful.

PDA Treatment Without other cardiac birth defects or pulmonary vascular disease, PDA occluded. Many spontaneously close in first few months, but rarely afterward. Endarteritis constant risk. Referred for closure. PGE inhibitors can be given to constrict the ductus (INDOMETHACIN) Surgical division or ligation or transcatheter techniques with an occluding device.

In the absence of other congenital cardiac abnormalities or severe pulmonary vascular disease, a PDA should generally be therapeutically occluded. Although many spontaneously close during the first months after birth, this rarely occurs later. Given the constant risk of endarteritis and the minimal complications of corrective procedures, even a small asymptomatic PDA is commonly referred for closure. For neonates and premature infants with congestive heart failure, a trial of prostaglandin synthesis inhibitors (e.g., indomethacin) can be administered in an attempt to constrict the ductus. Definitive closure can be accomplished by surgical division or ligation of the ductus or by transcatheter techniques in which an occluding device is placed.

ASD Pathophysiology uncomplicated: Left to Right shunt. normal babies: shortly after birth, RV becomes MORE COMPLIANT than LV (hypertrophy), which facilitates R to L shunt even more. Complications arise if RV compliance decreases over time (excessive load) or if pulmonary vascular disease occurs (eisenmanger syndrome), reversal of shunt.

In the case of an uncomplicated ASD, oxygenated blood from the left atrium is shunted into the right atrium, but not vice versa. Flow through the defect is a function of its size and the filling properties (compliance) of the ventricles into which the atria pass their contents. Normally after birth, the RV becomes more compliant than does the LV, owing to the regression of right ventricular wall thickness and an increase in LV thickness, facilitating the left-to-right directed shunt at the atrial level. The result is volume overload and enlargement of the right atrium and RV (see Fig. 16-11B). If right ventricular compliance diminishes over time (because of the excessive load), the left-to-right shunt may lessen. Occasionally, if severe pulmonary vascular disease develops (e.g., Eisenmenger syndrome), the direction of the shunt may actually reverse (causing right-to-left flow), such that desaturated blood enters the systemic circulation, resulting in hypoxemia and cyanosis.

A. Development of the Heart Tube FIG 16-1,2 mid-3rd week. MESODERMAL cells proliferate at cranial end of early embryonic disc. Eventually, these mesodermal cells form two longitudinal cell clusters known are ANGIOBLASTIC CORDS. These angioblastic cords canalize and become paired ENDOTHELIAL HEART TUBES. Lateral embryonic folding gradually causes these two tubes to oppose one another, allows them to FUSE IN VENTRAL MIDLINE, forming a SINGLE ENDOCARDIAL TUBE by day 22. LAYERS OF IT, inside to outside: endothelial lining that becomes ENDOCARDIUM, layer of gelatinous connective tissue (cardiac jelly), and a thick muscular layer derived from splanchnic mesoderm that develops into the MYOCARDIUM. Endocardial tube is continuous with aortic arch system rostrally, and the venous system caudally. Heart beat around day 22 or 23, with blood circulation beginning 4th week. The space overlying the developing cardiac area eventually becomes pericardial cavity-eventually housing the future hear.t

In the middle of the 3rd week of embryogenesis, mesodermal cells proliferate at the cranial end of the early embryonic disc. They eventually form two longitudinal cell clusters known as angioblastic cords. These cords canalize and become paired endothelial heart tubes (Fig. 16-1). Lateral embryonic folding gradually causes these two tubes to oppose one another and allows them to fuse in the ventral midline, forming a single endocardial tube by day 22. From inside to outside, the layers of this primitive heart tube are an endothelial lining that becomes the endocardium, a layer of gelatinous connective tissue (cardiac jelly), and a thick muscular layer that is derived from the splanchnic mesoderm and develops into the myocardium. The endocardial tube is continuous with the aortic arch system rostrally and with the venous system caudally. The primitive heart begins to beat around day 22 or 23, causing blood to circulate by the beginning of the 4th week. The space overlying the developing cardiac area eventually becomes the pericardial cavity, housing the future heart.

2. Transposition of the Great Arteries Each great vessel inappropriately arises from the opposite ventricle. ie. Aorta from RV. Pulmonary artery from LV. TGA most common cause of cyanosis in NEONATAL period. (cf Tetralogy of Fallot causes cyanosis after infancy) Theories: 1. Failure of aorticopulmonary septum to spiral in normal fashion during fetal development 2. abnormal growth and absorption of subpulmonary and subaortic infundibuli during truncus arteriosus division. Normally, reabsorption of subaortic infundibulum places forming aortic valve posterior and inferior to pulmonary valve, and in continuity with LV. TGA: process of infundibular reabsoprtion reversed, placing pulmonary valve over Lv instead.

In transposition of the great arteries (TGAs), each great vessel inappropriately arises from the opposite ventricle; that is, the aorta originates from the RV and the pulmonary artery originates from the LV (Fig. 16-19). This anomaly accounts for approximately 7% of congenital heart defects, affecting 40 of 100,000 live births. Whereas tetralogy of Fallot is the most common etiology of cyanosis after infancy, TGA is the most common cause of cyanosis in the neonatal period. The precise cause of transposition remains unknown. One theory contends that failure of the aorticopulmonary septum to spiral in a normal fashion during fetal development is the underlying problem. It has also been suggested that the defect may be the result of abnormal growth and absorption of the subpulmonary and subaortic infundibuli during the division of the truncus arteriosus. Normally, reabsorption of the subaortic infundibulum places the forming aortic valve posterior and inferior to the pulmonary valve and in continuity with the LV. In TGA, the process of infundibular reabsorption may be reversed, placing the pulmonary valve over the LV instead.

TofF Pathophysiology Subvalvular pulmonic stenosis increases resistance. Causes deox blood from system to DIVERT FROM RV through VSD TO LV. INTO SYSTEMIC CIRCULATION AGAIN, causing hypoxemia and cyanosis. Severity of stenosis determines amount of shunt. Resistances may effect it as well.

Increased resistance by the subvalvular pulmonic stenosis causes deoxygenated blood returning from the systemic veins to be diverted from the RV, through the VSD to the LV, and into the systemic circulation, resulting in systemic hypoxemia and cyanosis. The magnitude of shunt flow across the VSD is primarily a function of the severity of the pulmonary stenosis, but acute changes in systemic and pulmonary vascular resistances can affect it as well.

TGA Symptoms and Physical Examination BLUE on first day of life, gets worse as DA closes. RV HEAVE at lower sternal border as RV faces systemic procedures. Accentuated S2, closure of ANTERIORALLY placed AORTIC VALVE just under chest wall. No murmurs. Murmurs suggest an additional defect.

Infants with transposition appear blue, with the intensity of the cyanosis dependent on the degree of intermixing between the parallel circuits. In most cases, generalized cyanosis is apparent on the first day of life and progresses rapidly as the ductus arteriosus closes. Palpation of the chest reveals a right ventricular impulse at the lower sternal border as the RV faces systemic pressures. Auscultation may reveal an accentuated S2, which reflects closure of the anteriorly placed aortic valve just under the chest wall. Prominent murmurs are uncommon and may signal an additional defect.

PS Treatment mild- nothing moderate/severe: transcatheter balloon valvuloplasty. RVH usually regresses afterwards. Long term results not excellent uniformly.

Mild pulmonic stenosis usually does not progress or require treatment. Moderate or severe valvular obstruction at the valvular level can be relieved by dilating the stenotic valve by means of transcatheter balloon valvuloplasty. Long-term results of this procedure have been uniformly excellent, and right ventricular hypertrophy usually regresses subsequently.

ASD Symptoms murmur during childhood or adolescence. Asymptomatic at birth. TIRED, SICK. Dyspnea on exertion, fatigue, recurrent lower respiratory tract infections. BUTTERFLY. palpitations due to atrial tachyarrhythmias resulting from right atrial enlargement.

Most infants with ASDs are asymptomatic. The condition may be detected by the presence of a murmur on routine physical examination during childhood or adolescence, but the exam findings are subtle and 25% of ASDs are not diagnosed until adulthood. If symptoms do occur, they include dyspnea on exertion, fatigue, and recurrent lower respiratory tract infections. The most common symptoms in adults are decreased stamina and palpitations due to atrial tachyarrhythmias resulting from right atrial enlargement.

ASD Treatment Elective surgery if volume of blood is significant. To prevent heart failure/chronic pulmonary vascular disease. Use direct suture or pericardial/synthetic patch. Percutaneous repair: closure device via intravenous catheter= for selected SECUNDUM ASDS.

Most patients with ASDs remain asymptomatic. However, if the volume of shunted blood is hemodynamically significant (even in the absence of symptoms), elective surgical repair is recommended to prevent the development of heart failure or chronic pulmonary vascular disease. The defect is repaired by direct suture closure or with a pericardial or synthetic patch. In children and young adults, morphologic changes in the right heart often return to normal after repair. Percutaneous ASD repair, using a closure device deployed via an intravenous catheter, is a less invasive alternative to surgery in selected patients with secundum ASDs.

5. Pulmonic Stenosis congenitally fused valve commisures, RV outflow tract, pulmonary artery all can produce narrowing of RV outlet.

Obstruction to right ventricular outflow may occur at the level of the pulmonic valve (e.g., from congenitally fused valve commissures), within the body of the RV (i.e., in the RV outflow tract), or in the pulmonary artery. Valvular pulmonic stenosis is the most frequent form (Fig. 16-15).

ASD Diagnostic Studies CXR: Enlarged heart RA and RV dilatation. Pulmonary artery prominent with increased pulmonary vascular marking. ECG: RVH, RA enlargement, incomplete or complete RBBB. In Ostium Primum type: LEFT AXIS DEVIATION is common-result of displacement and hypoplasia of LBB anterior fascicle. Echo: R A and V enlarged. Translatorial shunt and magnitude and direction of flow seen by Doppler. Cardiac cath rarely necessary. pulmonary vascular resistance, coronary artery disease concurrently. O2 sat: RA=SVC in ASD: RA>>>>SVC because L to R shunt of well-oxygenated blood.

On chest radiograph, the heart is usually enlarged because of right atrial and right ventricular dilatation, and the pulmonary artery is prominent with increased pulmonary vascular markings. The electrocardiogram (ECG) shows right ventricular hypertrophy, often with right atrial enlargement and incomplete or complete right bundle branch block. In patients with the ostium primum type of ASD, left axis deviation is common and is thought to be a result of displacement and hypoplasia of the left bundle branch's anterior fascicle. Echocardiography demonstrates right atrial and right ventricular enlargement; the ASD may be visualized directly, or its presence may be implied by the demonstration of a transatrial shunt by Doppler flow assessment. The magnitude and direction of shunt flow and an estimation of right ventricular systolic pressure can also be determined by echo Doppler measurements. Given the high sensitivity of echocardiography, it is rarely necessary to perform cardiac catheterization to confirm the presence of an ASD. However, catheterization may be useful to assess pulmonary vascular resistance and to diagnose concurrent coronary artery disease in older adults. In a normal person undergoing cardiac catheterization, the oxygen saturation measured in the right atrium is similar to that in the superior vena cava. However, an ASD with left-to-right shunting of well-oxygenated blood causes the saturation in the right atrium to be much greater than that of the superior vena cava.

VSD Diagnostic Studies CXR: normal with small defect, Large defects: cardiomegaly and prominent pulmonary vascular markings With pulmonary vascular resistance disease: enlarged pulmonary arteries, peripheral tapering ECG: LA, LV enlargement with LARGE SHUNT. RVH if PULMONARY vascular disease has developed. Location and amount of VSD, RVSystolic pressure: echo with doppler. O2 Sat: cardiac cath RV >> RA because highly oxygenated blood is shunted from LV into RV.

On chest radiographs, the cardiac silhouette may be normal in patients with small defects, but in those with large shunts, cardiomegaly and prominent pulmonary vascular markings are present. If pulmonary vascular disease has developed, enlarged pulmonary arteries with peripheral tapering may be evident. The ECG shows left atrial enlargement and left ventricular hypertrophy in those with a large shunt, and right ventricular hypertrophy is usually evident if pulmonary vascular disease has develop ped. Echocardiography with Doppler studies can accurately determine the location of the VSD, identify the direction and magnitude of the shunt, and provide an estimate of right ventricular systolic pressure. Cardiac catheterization demonstrates increased oxygen saturation in the RV compared with the right atrium, the result of shunting of highly oxygenated blood from the LV into the RV.

Eisenmenger Syndrome Physical Examination Cyanotic Digital clubbing a wave in JVP (R Pressure HIGH during contraaction) Loud P2 Murmur of INCITING LEFT TO RIGHT shunt is ABSENT because original pressure gradient is negated by elevated right Heart Pressures

On examination, a patient with Eisenmenger syndrome appears cyanotic with digital clubbing. A prominent a wave in the jugular venous pulsation reflects elevated right-sided pressure during atrial contraction. A loud P2 is common. The murmur of the inciting left-to-right shunt is usually absent, because the original pressure gradient across the lesion is negated by the elevated right-heart pressures.

CA Physical Examination WEAK FEMORAL PULSES, DELAYED. ELEVATED BP IN UPPER BODY coarctation proximal to L subclavian takeoff from aorta, SBP in RIGHT ARM HIGHER. coarctation distal to L subclavian takeoff from aorta, SBP in ARMS HIGHER THAN LEGS vs. normal, when legs higher than arms. MIDSYSTOLIC EJECTION MURMUR turbulent flow through coarctation OVER THE CHEST OR BACK Tortuous collateral arterial circulation may create continuous murmurs over the chest in adults.

On examination, the femoral pulses are weak and delayed. An elevated blood pressure in the upper body is the most common finding. If the coarctation occurs distal to the takeoff of the left subclavian artery, the systolic pressure in the arms is greater than that in the legs. If the coarctation occurs proximal to the takeoff of the left subclavian artery, the systolic pressure in the right arm may exceed that in the left arm. A systolic pressure in the right arm that is 15 to 20 mm Hg greater than that in a leg is sufficient to suspect coarctation, because normally the systolic pressure in the legs is higher than that in the arms. A midsystolic ejection murmur (caused by turbulent flow through the coarctation) may be audible over the chest and/or back. A prominent tortuous collateral arterial circulation may create continuous murmurs over the chest in adults.

CA Symptoms Severe: heart failure shortly after birth. PDA ALONG WITH COARCTATION OF AORTA: upper body well perfused lower body gets blood from right to left flow of poorly oxygenated blood from pulmonary artery across PDA, into descending aorta beyond the coarctation. Could be asymptomatic with mild. Later in life, upper extremity hypertension.

Patients with severe coarctation usually present very shortly after birth with symptoms of heart failure. Infants may also exhibit differential cyanosis if the ductus arteriosus fails to constrict and remains patent. The upper half of the body, supplied by the LV and the ascending aorta, is perfused with well-oxygenated blood; however, the lower half appears cyanotic because it is largely supplied by right-to-left flow of poorly oxygenated blood from the pulmonary artery, across the PDA, and into the descending aorta, beyond the coarctation. When the coarctation is less severe, a patient may be asymptomatic or experience only mild weakness or pain in the lower extremities following exercise (i.e., claudication). In asymptomatic cases, coarctation may be suspected by the finding of upper extremity hypertension later in life (see Chapter 13).

VSD Symptoms small: asymptomatic. Large: heart failure, etc as an infant in 10% With Eisenmenger: cyanosis and dyspnea. Bacterial endocarditis can occur, regardless of SIZE.

Patients with small VSDs typically remain symptom free. Conversely, 10% of infants with VSDs have large defects and develop early symptoms of heart failure, including tachypnea, poor feeding, failure to thrive, and frequent lower respiratory tract infections. Patients with VSDs complicated by pulmonary vascular disease and reversed shunts may present with dyspnea and cyanosis. Bacterial endocarditis (see Chapter 8) can develop, regardless of the size of the VSD.

C. Septation Weeks 4-6 Simultaneous septation of atria and ventricles.

Septation of the developing atrium, AV canal, and ventricle occurs between the 4th and 6th weeks. Although these events are described separately here, they actually occur simultaneously.

Holt-Oram Syndrome TBX5, transcription factor gene, HOLT ORAM SYNDROME- aka HEART HAND SYNDROME AUTOSOMAL DOMINANT, secundum ASDs, VSDs. Nkx2.5 transcription factor gene(heritable ASDs) GATA4 transcription factor gene (familial septal defect syndromes)

Several other transcription factors involved in heart development likely contribute to congenital heart disease. Some families with heritable forms of ASDs have mutations in the transcription factor gene Nkx2.5. An associated transcription factor gene GATA4 appears to collaborate with Nkx2.5 and has also been implicated in familial septal defect syndromes. Mutations in TBX5, yet another transcription factor gene, are responsible for Holt-Oram syndrome (also known as the heart-hand syndrome), an autosomal dominant disorder whose characteristic cardiac defects include secundum ASDs and VSDs.

TGA Treatment Emergency! Maintain DA by PGE infusion. Create interatrial communication via balloon catheter (Rashkind procedure)....until surgery Arterial switch operation, just above semilunar valves, arteries are moved. coronary arteries relocated to new aorta as well.

TGA is a medical emergency. Initial treatment includes maintenance of the ductus arteriosus by prostaglandin infusion and creation of an interatrial communication using a balloon catheter (termed the Rashkind procedure). Such intervention allows adequate mixing of the two circulations until definitive corrective surgery can be performed. The current corrective procedure of choice is the "arterial switch" operation (Jatene procedure), which involves transection of the great vessels above the semilunar valves and origin of the coronary arteries. The great vessels are then reversed to the natural configuration, so the aorta arises from the LV and the pulmonary artery arises from the RV. The coronary arteries are then relocated to the new aorta.

TGA Pathophysiology TGA separates pulmonary and systemic circulations by placing two circuits in parallel rather than series. deoxygenated blood stays in systemic circulation (SVC/IVC to RA to RV to AORTA to system to SVC/IVC) FORCES DESATURATED BLOOD FROM SYSTEMIC VENOUS SYSTEM to pass through RV then return to systemic circulation through aorta WITHOUT OXYGENATION IN LUNGS. OXYGENATED BLOOD stays in pulmonic circulation (Pulmonary veins to LA to LV to Pulmonary artery to lungs to pulmonary veins) SEVERELY HYPOXIC CYANOTIC NEONATE. lethal without intervention. OK In uterus because flow through Ductus arteriosus and foramen ovale allows communication between the two circulations. Oxygenated fetal blood flows form placenta through umbilical vein to RA, where MOST FLOWS THROUGH FORAMEN OVALE TO LA...... to LV to pulmonary artery. From pulmonary artery, most goes through ductus arteriosus into the aorta (avoiding high resistance pulmonary vessels)= so systemic tissues receive oxygenated blood. At birth, physiological closure of FO and DA eliminates shunt between parallel circulations. If either remains patent (naturally or with exogenous PGEs or surgery), kiddo survives.

TGA separates the pulmonary and systemic circulations by placing the two circuits in parallel rather than in series. This arrangement forces desaturated blood from the systemic venous system to pass through the RV and then return to the systemic circulation through the aorta without undergoing normal oxygenation in the lungs. Similarly, oxygenated pulmonary venous return passes through the LV and then back through the pulmonary artery to the lungs without imparting oxygen to the systemic circulation. The result is an extremely hypoxic, cyanotic neonate. Without intervention to create mixing between the two circulations, TGA is a lethal condition. TGA is compatible with life in utero because flow through the ductus arteriosus and foramen ovale allows communication between the two circulations. Oxygenated fetal blood flows from the placenta through the umbilical vein to the right atrium, and then most of it travels into the left atrium through the foramen ovale. The oxygenated blood in the left atrium passes into the LV and is pumped out the pulmonary artery. Most of the pulmonary artery flow travels through the ductus arteriosus into the aorta, instead of the high-resistance pulmonary vessels, such that oxygen is provided to the developing tissues. After birth, normal physiologic closure of the ductus and the foramen ovale eliminates the shunt between the parallel circulations and, without intervention, would result in death because oxygenated blood does not reach the systemic tissues. However, if the ductus arteriosus and foramen ovale remain patent (either naturally or with exogenous prostaglandins or surgical intervention), communication between the parallel circuits is maintained, and sufficiently oxygenated blood may be provided to the brain and other vital organs.

1. Tetralogy of Fallot CAUSE: an abnormal anterior and cephalad displacement of the INFUNDIBULAR(outflow tract) portion of the INTERVENTRICULAR septum. 4 anomalies occur as a consequence: 1. VSD (anterior malalignment of IVS) 2. Subvalvular pulmonic stenosis (obstruction from displaced infundibular septum, often with valvular pulmonic stenosis) 3. Overriding aorta, receives blood from BOTH VENTRICLES 4. RVH (High pressure load on RV by pulmonic stenosis) MOST common form of cyanotic congenital heart disease. microdeletion in chromosome 22 (22q11) in all patients with a syndrome that includes tofF as one of the CV manifestations.

Tetralogy of Fallot results from a single developmental defect: an abnormal anterior and cephalad displacement of the infundibular (outflow tract) portion of the interventricular septum. As a consequence, four anomalies arise that characterize this condition, as shown in Figure 16-18: (1) a VSD caused by anterior malalignment of the interventricular septum, (2) subvalvular pulmonic stenosis because of obstruction from the displaced infundibular septum (often with valvular pulmonic stenosis), (3) an overriding aorta that receives blood from both ventricles, and (4) right ventricular hypertrophy owing to the high-pressure load placed on the RV by the pulmonic stenosis. Tetralogy of Fallot is the most common form of cyanotic congenital heart disease after infancy, occurring in 5 of 10,000 live births and is often associated with other cardiac defects, including a right-sided aortic arch (25% of patients), ASD (10% of patients), and less often, an anomalous origin of the left coronary artery. A microdeletion in chromosome 22 (22q11) has been identified in patients with a syndrome that includes tetralogy of Fallot as one of the cardiovascular manifestations (see Box 16-1).

PS Diagnostic Studies CXR: enlarged RA and RV. Post-stenotic pulmonary artery dilation. caused by high velocity jet of blood weakening portion of pulmonary artery. ECG: RVH, right axis deviation. Echo with doppler: pulmonary valve morphology, RVH, pressure gradient across obstruction.

The chest radiograph may demonstrate an enlarged right atrium and ventricle with poststenotic pulmonary artery dilation (thought to be caused by the impact of the high-velocity jet of blood against the wall of the pulmonary artery). The ECG shows right ventricular hypertrophy with right axis deviation. Echocardiography with Doppler imaging assesses the pulmonary valve morphology, determines the presence of right ventricular hypertrophy, and accurately measures the pressure gradient across the obstruction.

AS Diagnostic Studies CXR: enlarged LV and dilated ascending aorta. ECG: LVH Echo: abnormal aortic valve, degree of LVH. Doppler- pressure gradienta cross stenotic valve, allow calculation of valve area. Cardiac cath. confirms pressure gradient across valve.

The chest radiograph of an infant with AS may show an enlarged LV and a dilated ascending aorta. The ECG often shows left ventricular hypertrophy. Echocardiography identifies the abnormal structure of the aortic valve and the degree of left ventricular hypertrophy. Doppler assessment can accurately measure the pressure gradient across the stenotic valve and allow calculation of the valve area. Cardiac catheterization confirms the pressure gradient across the valve.

AS Symptoms Less than 10% HF before age 1. Most AS children develop normally.

The clinical picture of AS depends on the severity of the lesion. Fewer than 10% of infants experience symptoms of heart failure before age 1, but if they do, they manifest tachycardia, tachypnea, failure to thrive, and poor feeding. Most older children with congenital AS are asymptomatic and develop normally. When symptoms do occur, they are similar to those of adult AS and include fatigue, exertional dyspnea, angina pectoris, and syncope (see Chapter 8).

PS Pathophysiology leads to increased RV pressures, and thus RVH. mild generally stays constant. severe can cause R sided heart failure.

The consequence of pulmonic stenosis is impairment of right ventricular outflow, which leads to increased RV pressures and chamber hypertrophy. The clinical course is determined by the severity of the obstruction. Although mild pulmonic stenosis rarely progresses and is unlikely to affect RV function, untreated severe pulmonic stenosis typically results in right-sided heart failure

3. Patent Ductus Arteriosus LEFT TO RIGHT SHUNT (after birth, and before pulmonary disease involvement=aorta to pulmonary artery) Fetally, connects pulmonary artery to descending aorta. Fails to close after birth: connection of great vessels.... Rubella, prematurity, birth at high altitude are risk factors.

The ductus arteriosus is the vessel that connects the pulmonary artery to the descending aorta during fetal life. PDA results when the ductus fails to close after birth, resulting in a persistent connection between the great vessels (Fig. 16-13). It has an overall incidence of about 1 in 2,500 to 5,000 live term births. Risk factors for its presence include first trimester maternal rubella infection, prematurity, and birth at a high altitude.

III. Fetal and Transitional Circulations

The fetal circulation elegantly serves the needs of in utero development. At birth, the circulation automatically undergoes modifications that establish the normal blood flow pattern of a newborn infant.

VSD Pathophysiology Relative resistances to flow and consequences: small: defect itself>>pulmonary or systemic vasculatures, shunting largely prevented. larger nonrestrictive defects: pulmonary or systemic vasculatures may be > defect itself, shunting volume determined by these resistances. BEFORE birth, largely determined by pulmonary resistance, which is equal to systemic resistance. AFTER BIRTH, pulmonary vascular resistance FALLS, INCREASING LEFT TO RIGHT SHUNT. WHEN shunt is large: RV, pulm circ, LA, and LV all volume overloaded.!!!!!!!WHOLE HEART INCREASED BLOOD RETURN to LV augments stroke volume via Frank-Starling. But eventually, increased vol load results in progressive chamber dilatation, systolic dysfunction, symptoms of heart failure. As pulmonary vascular resistance rises because of augmented circulation through pulmonary.... Eisenmenger may occur.

The hemodynamic changes and magnitude of the shunt that accompany VSDs depend on the size of the defect and the relative resistances of the pulmonary and systemic vasculatures. In small VSDs, the defect itself offers more resistance to flow than the pulmonary or systemic vasculature, thereby preventing a significant quantity of left-to-right shunting. Conversely, with larger "nonrestrictive" defects, the volume of the shunt is determined by the relative pulmonary and systemic vascular resistances. In the perinatal period, the pulmonary vascular resistance approximates the systemic vascular resistance, and minimal shunting occurs between the two ventricles. After birth, however, as the pulmonary vascular resistance falls, an increasing left-to-right shunt through the defect develops. When this shunt is large, the RV, pulmonary circulation, left atrium, and LV experience a relative volume overload. Initially, the increased blood return to the LV augments stroke volume (via the Frank-Starling mechanism); but over time, the increased volume load can result in progressive chamber dilatation, systolic dysfunction, and symptoms of heart failure. In addition, the augmented circulation through the pulmonary vasculature can cause pulmonary vascular disease as early as 2 years of age. As pulmonary vascular resistance eventually approaches or exceeds systemic resistance, the intracardiac shunt may reverse its direction (i.e., Eisenmenger syndrome), leading to systemic hypoxemia and cyanosis.

Eisenmanger Syndrome Pathophysiology Histology: Pulmonary arteriolar media hypertrophies, intima proliferates, reducing cross-sectional area of pulmonary vascular bed. Over time, essels become thrombosed, resistance of pulmonary vasculature rises, original LEFT TO RIGHT SHUNT DECREASES, eventually, the resistance exceeds the sytemic vasculatrue, and direction of shunt flow reverses.

The mechanism by which increased pulmonary flow causes this condition is unknown. Histologically, the pulmonary arteriolar media hypertrophies and the intima proliferates, reducing the cross-sectional area of the pulmonary vascular bed. Over time, the vessels become thrombosed, and the resistance of the pulmonary vasculature rises, causing the original left-to-right shunt to decrease. Eventually, if the resistance of the pulmonary circulation exceeds that of the systemic vasculature, the direction of shunt flow reverses.

PDA Physical Examination CONTINUOUS MACHINE LIKE MURMUR at left SUBCLAVICULAR REGION. Throughout cardiac cycle. Pressure gradient between pulmonary artery and aorta in both systole and diastole. If pulmonary vessels become diseased-diminished gradient because pulmonary resistance increases, diminishing the murmur (diastolic portion may disappear) If Eisenmenger syndrome develops: cyanosis, clubbing in lower extremity.

The most common finding in a patient with a left-to-right shunt through a PDA is a continuous, machine-like murmur (see Fig. 2-10), heard best at the left subclavicular region. The murmur is present throughout the cardiac cycle because a pressure gradient exists between the aorta and pulmonary artery in both systole and diastole. However, if pulmonary vascular disease develops, the gradient between the aorta and the pulmonary artery decreases, leading to diminished flow through the PDA, and the murmur becomes shorter (the diastolic component may disappear). If Eisenmenger syndrome develops, lower extremity cyanosis and clubbing may be present as poorly oxygenated blood is shunted to the descending aorta.

VSD Physical Examination HARSH HOLOCYSTOLIC MURMUR at LEFT STERNAL BORDER. (NOT APEX like MR???) As pulmonary vascular disease develops, pressure gradient between LV and RV (raised due to increased pulmonary pressure) is less dramatic, so murmur quiets. This will increase SIZE OF RIGHT HEART. Smaller defects = LOUDER MURMURS Mid-systolic rumbling murmur can often be heard at apex owing to increased flow across mitral valve (because more blood is returned to the left side of the heart from the pulmonary circulation(because more was sent that way originally by leaking through VSD)) ?????????

The most common physical finding is a harsh holosystolic murmur that is best heard at the left sternal border. Smaller defects tend to have the loudest murmurs because of the great turbulence of flow that they cause. A systolic thrill can commonly be palpated over the region of the murmur. In addition, a mid-diastolic rumbling murmur can often be heard at the apex owing to the inc reased flow across the mitral valve. If pulmonary vascular disease develops, the holosystolic murmur diminishes as the pressure gradient across the defect decreases. In such patients, an RV heave, a loud pulmonic closure sound (P2), and cyanosis may be evident.

PS Physical Examination if accompanied by RVH: prominent JV "a wave" and an RV HEAVE. Loud, late peaking CRESCENDO DECRESCENDO SYSTOLIC ejection murmur at UPPER LEFT STERNAL BORDER, often with a palpable thrill. Widened splitting of S2 and soft P2 because DELAYED CLOSURE OF STENOTIC PULMONARY VALVE. pulmonic ejection click follows S2, precedes systolic murmur during early phase of RV contraction as stenotic valve leaflets suddenly reach max level of ascend into pulmonary artery, just before blood ejection. *Unlike other Right sided sounds and murmurs, this sound DIMINISHES WITH INSPIRATION (augmented R sided filling elevates leaflets into pulmonary artery prior to RV contraction, preempting rapid tensing in early systole that produces the sound.

The physical findings in pulmonic stenosis depend on the severity of the obstruction. If the stenosis is severe with accompanying right ventricular hypertrophy, a prominent jugular venous a wave can be observed (see Chapter 2) and an RV heave is palpated over the sternum. A loud, late-peaking, crescendo-decrescendo systolic ejection murmur is heard at the upper left sternal border, often associated with a palpable thrill. Widened splitting of the S2 with a soft P2 component is caused by the delayed closure of the stenotic pulmonary valve. In more moderate stenosis, a pulmonic ejection sound (a high-pitched "click") follows S1 and precedes the systolic murmur. It occurs during the early phase of right ventricular contraction as the stenotic valve leaflets suddenly reach their maximum level of ascent into the pulmonary artery, just before blood ejection. Unlike other sounds and murmurs produced by the right side of the heart, the pulmonic ejection sound diminishes in intensity during inspiration. This occurs because with inspiration, the augmented right-sided filling elevates the leaflets into the pulmonary artery prior to RV contraction, preempting the rapid tensing in early systole that is thought to produce the sound.

Septation of Atria FIG 16-4 1. SEPTUM PRIMUM (the primary atrial septum) Begins as a RIDGE of tissue on roof of common atrium that grows DOWNWARD, leaving a large opening OSTIUM PRIMUM BETWEEN CRESCENT SHAPED LEADING EDGE OF SEPTUM and THE ENDOCARDIAL CUSHIONS SURROUNDING THE AV CANAL. This allows passage of blood between atria. 2. OSTIUM SECUNDUM is coalesced hole formed from many small openings that form in the center of the septum primum as it is closing off. This leaves communication between atria. 3. septum primum fuses with superior endocardial cushions. 4. SEPTUM SECUNDUM, more muscular, second membrane develops to the RIGHT of the superior aspect of the septum primum. Overlaps ostium secundum. 5. Septum secundum fuses with endocardial cushions, leaving the FORAMEN OVALE open. Superior edge of septum primum regresses, leaving a flap like valve that allows only Right to Left flow through foramen ovale. In fetal heart: RA(higher pressure) to LA (lower pressure). Pressures reverse at birth, causing valve to close. FIG 16-5

The primary atrial septum, also known as the septum primum, begins as a ridge of tissue on the roof of the common atrium that grows downward into the atrial cavity (Fig. 16-4). As the septum primum advances, it leaves a large opening known as the ostium primum between the crescent-shaped leading edge of the septum and the endocardial cushions surrounding the AV canal. The ostium primum allows passage of blood between the forming atria. Eventually, the septum primum fuses with the superior aspect of the endocardial cushions (described in more detail in the next section), obliterating the ostium primum. However, before closure of the ostium primum is complete, small perforations appear in the center of the septum primum that ultimately coalesce to form the ostium secundum, preserving a pathway for blood flow between the atria (see Fig. 16-4). Following closure of the ostium primum, a second, more muscular membrane, the septum secundum, begins to develop immediately to the right of the superior aspect of the septum primum. This septum grows downward and overlaps the ostium secundum. The septum secundum eventually fuses with the endocardial cushions, although only in a partial fashion, leaving an oval-shaped opening known as the foramen ovale. The superior edge of the septum primum then gradually regresses, leaving the lower edge to act as a "flap-like" valve that allows only right-to-left flow through the foramen ovale (Fig. 16-5). During gestation, blood passes from the right atrium to the left atrium because the pressure in the fetal right atrium is greater than that in the left atrium. This pressure gradient changes direction postnatally, causing the valve to close, as described later.

1. Semilunar Valve Development (A + P) FIG 16-9 Start just before aorticopulmonary septum is complete. 1. begins as three outgrowths of SUBENDOCARDIAL MESENCHYMAL TISSUE form around both aortic and pulmonary orifices. 2. They are shaped and excavated by: PROGRAMMED CELL DEATH and BLOOD FLOW. Create the three thin-walled cusps of the aortic and pulmonary valves. 3. including degeneration of myocardium and replacement by connective tissue that forms the chordae tendineae; their muscular attachments to the ventricular wall are the papillary muscles.

The semilunar valves start to develop just before the completion of the aorticopulmonary septum. The process begins when three outgrowths of subendocardial mesenchymal tissue form around both the aortic and pulmonary orifices. These growths are ultimately shaped and excavated by the joint action of programmed cell death and blood flow to create the three thin-walled cusps of both the aortic and pulmonary valves.

Eisenmenger Syndrome Treatment Avoid exacerbation of RIGHT TO LEFT SHUNT: PA, altitude, peripheral vasodilator drugs, pregnancy. Prompt treatment of infections, rhythm disturbances, phlebotomy with erythrocytosis. Pulmonary vasodilators perhaps. ENDOTHELIN RECEPTOR ANTAGONISTs, PROSTACYCLIN ANALOGS, PDE Inhibitors. Lung or heart lung transplantation is only definitive long term strategy.

Treatment includes the avoidance of activities that can exacerbate the right-to-left shunt. These include strenuous physical activity, high altitude, and the use of peripheral vasodilator drugs. Pregnancy is especially dangerous; the rate of spontaneous abortion is 20% to 40%, and the incidence of maternal mortality is approximately 45%. Supportive measures for Eisenmenger syndrome include prompt treatment of infections, management of rhythm disturbances, and phlebotomy for patients with symptomatic erythrocytosis. lthough there are no remedies that reverse the disease process in Eisenmenger syndrome, pulmonary vasodilator therapy can provide symptomatic relief and improve the patient's quality of life. Effective agents include endothelin receptor antagonists, prostacyclin analogs, and phosphodiesterase inhibitors (see Chapter 17). The only effective long-term strategy for severely affected patients is lung or heart-lung transplantation. Fortunately, with the dramatic advances that have been made in the detection and early correction of severe congenital heart defects, Eisenmenger syndrome has become less common.

Turner Syndrome Left sided obstructive congenital heart lesions: Bicuspid aortic valve Coarctation of aorta Occasional hypoplastic left heart syndrome (underdeveloped LV and aorta).

Turner syndrome (45, XO) is another heritable condition associated with congenital heart disease. Left-sided obstructive congenital heart lesions are common in patients with this syndrome, including bicuspid aortic valve, coarctation of the aorta, and occasionally hypoplastic left heart syndrome (underdevelopment of the LV and aorta). The specific genes responsible for these abnormalities have not yet been elucidated.

PDA Diagnostic Studies CXR: ENLARGEED CARDIAC SILHOUETTE ( LA and LV enlargement) Prominent pulmonary vascular markings. Calcificaiton of ductus may be visualize.d ECG: LA enlargement, LVH with a large shunt.. Echo: doppler visualize defect, estimate R sided systolic pressures, see flow through it. Cath unnecessary for diatnostic. O2 sat: in ANY LEFT TO RIGHT SHUNT: Pulmonary artery > RV

With a large PDA, the chest radiograph shows an enlarged cardiac silhouette (left atrial and left ventricular enlargement) with prominent pulmonary vascular markings. In adults, calcification of the ductus may be visualized. The ECG shows left atrial enlargement and left ventricular hypertrophy when a large shunt is present. Echocardiography with Doppler imaging can visualize the defect, demonstrate flow through it, and estimate right-sided systolic pressures. Cardiac catheterization is usually unnecessary for diagnostic purposes. When performed in patients with a left-to-right shunt, it demonstrates a step up in oxygen saturation in the pulmonary artery compared with the RV, and angiography shows the abnormal flow of blood through the PDA.

Eisenmenger Syndrome Symptoms Hypoxemia, dyspnea fatigue. Reduced Hb sat makes more bone marrow RBCs, leading to hyperviscosity: fatigue, headaches, stroke. Infarction or rupture of pulmonary vessels- hemoptysis.

With reversal of the shunt to the right-to-left direction, symptoms arise from hypoxemia, including exertional dyspnea and fatigue. Reduced hemoglobin saturation stimulates the bone marrow to produce more red blood cells (erythrocytosis), which can lead to hyperviscosity, symptoms of which include fatigue, headaches, and stroke (caused by cerebrovascular occlusion). Infarction or rupture of the pulmonary vessels can result in hemoptysis.