History

The female:male ratio is at least 2:1 in patients with an ostium secundum atrial septal defect,⁵⁷ and the gender ratio in sinus venosus defects and in ostium primum defects is approximately equal.¹³ Ostium secundum atrial septal defects are sometimes familial, can recur in a several generations,^65,66 and have been found in identical twins.⁶⁷ Familial scimitar syndrome has been reported.^68,69 Autosomal dominant inheritance is a feature of atrial septal defect with the Holt-Oram syndrome (see section Physical Appearance).⁷⁰ Autosomal dominant inheritance tends to be the mode in inheritance in ostium secundum defects with prolonged atrioventricular conduction.^71–73 In some members of a family, the atrial septal defect occurs with PR interval prolongation; other family members have PR prolongation with an intact atrial septum⁷¹; and still others experience sudden death. Mutations in the NKX2.5 gene have been associated with familial atrial septal defect and progressive prolongation of atrioventricular conduction.⁷⁴ Concordant familial segregation of atrial septal defect has been reported with the Axenfeld-Reiger Anomaly (see section Physical Appearance).⁷⁵

Atrial septal defects may go unrecognized for decades because symptoms are mild or absent and physical signs are subtle.¹³ The soft pulmonary midsystolic flow murmur in children and young adults is often dismissed as innocent (see Chapter 2). Conversely, an atrial septal defect may first come to light in a routine chest x-ray.⁷⁶ An important exception is the symptomatic infant with an ostium secundum atrial septal defect (see Figure 15-46B) and congestive heart failure followed by spontaneous closure (see previous).^26,27,57

About half of patients with a scimitar syndrome are either asymptomatic or only mildly symptomatic when the diagnosis is made, despite varying degrees of hypoplasia of the right lung (see Figures 15-8, 15-9, and 15-10).^36,38 However, a small but important group of patients with scimitar syndrome consists of symptomatic infants with cyanosis and pulmonary hypertension.³⁶ Older children and young adults come to light because an x-ray discloses the scimitar sign and the hypoplastic right lung or because of an atrial tachyarrhythmia, recurrent lower respiratory infections, or a murmur.^36,38,77

Paul Wood remarked, “In any series of geriatric necropsies atrial septal defect is always represented.”⁷⁸ Ostium secundum atrial septal defects are among the most common congenital cardiac malformations in adults and account for 30% to 40% of patients over 40 years of age who have not undergone an operation.^13,79–81 Patients often survive to advanced age, but life expectancy is not normal. Three quarters of patients are alive through the third decade, but three quarters are dead by age 50 years and 90% are dead by age 60 years.⁷⁹ Sporadic survivals have been recorded beyond age 70 years, and rare examples are found of patients in their 80s or 90s (see Figure 15-43B).^80–83 An exceptional case was a patient who died 3 months before his 95th birthday (see Figure 15-43A).⁸⁰ Death is often unrelated to the malformation, but when a relationship exists, cardiac failure is the most common cause.

Figure 15-43 A, X-ray from the 95-year-old acyanotic man with a nonrestrictive ostium secundum atrial septal defect. The electrocardiogram (see Figure 15-32) shows atrial fibrillation. Pulmonary arterial and pulmonary venous vascularity are increased. The pulmonary trunk (PT) is dilated, but the ascending aorta is not border-forming. The right atrium (RA) and the right ventricle (RV) are strikingly enlarged. B, X-ray from an 87-year-old acyanotic woman with a nonrestrictive ostium secundum atrial septal defect, severe tricuspid regurgitation, and atrial fibrillation. Pulmonary vascularity is decreased. The pulmonary trunk (PT) is dilated, and the enlarged right branch contains eggshell calcification. The ascending aorta is not border-forming. The right atrium (RA) and right ventricle (RV) are strikingly enlarged. At necropsy, there was a large thrombus in the dilated right pulmonary artery and a smaller thrombus in the dilated left pulmonary artery.

The clinical course of ostium secundum atrial septal defects spans the reproductive years, and most patients are female. It is therefore reassuring that, despite the gestational increase in cardiac output and stroke volume, young gravida with an atrial septal defect generally endure pregnancy, even multiple pregnancies, without tangible ill effects.⁸⁴ However, brisk hemorrhage during delivery provokes a rise in systemic vascular resistance and a fall in systemic venous return, a combination that augments the left-to-right shunt, sometimes appreciably.⁸⁴ There is also a peripartum risk of paradoxical embolization from leg veins or pelvic veins because emboli carried by the inferior vena cava traverse the atrial septal defect and enter the systemic circulation.⁸⁴

Dyspnea and fatigue are early symptoms of an ostium secundum atrial septal defect. The large left-to-right shunt is responsible for a decrease in pulmonary compliance and an increase in the work of breathing. Orthopnea may be experienced because the supine position increases the work of breathing in patients with reduced lung compliance. Platypnea-orthodeoxia is a rare syndrome characterized by orthostatic provocation of a right-to-left shunt across an atrial septal defect or a patent foramen ovale.^85,86 Platypnea (dyspnea induced by the upright position and relieved by recumbency) and orthodeoxia (arterial desaturation in the upright position with improvement during recumbency) are features of this rare disorder. Clinical suspicion may originate from the patient who reports that dyspnea is provoked by standing upright.

Recurrent lower respiratory infections are common, especially in children. Although the pulmonary valve is theoretically susceptible to infective endocarditis because of the rapid rate of ejection, only a single case has been reported.⁸⁷

The conditions of older patients deteriorate chiefly on three counts. First, a decrease in left ventricular distensibility associated with aging, ischemic heart disease, systemic hypertension, or acquired calcific aortic stenosis augments the left-to-right shunt.^81,88 Second, an age-related increase in prevalence of paroxysmal atrial tachycardia, atrial fibrillation, and atrial flutter precipitates congestive heart failure (see Figure 15-45).⁸⁹ Third, mild to moderate pulmonary hypertension in older adults occurs with a persistent left-to-right shunt, so the aging right ventricle is doubly beset by both pressure and volume overload. Pulmonary vascular disease with reversed shunt is believed to represent the coincidence of primary pulmonary hypertension with an ostium secundum atrial septal in young females who are predisposed to both lesions (see Figure 15-13; see previous).⁵⁹ Importantly, the outlook is better when primary pulmonary hypertension occurs with an atrial septal defect or a patent foramen ovale that permits the right heart to decompress (see Chapter 14).

Figure 15-45 X-rays from an acyanotic woman with an ostium secundum atrial septal defect before and after the onset of atrial fibrillation. A, At age 49 years, the x-ray shows increased pulmonary arterial vascularity, mild prominence of the pulmonary trunk and its right branch, and a moderate increase in right atrial size. B, After the onset of atrial fibrillation 4 years later, there is a considerable increase in size of the pulmonary trunk, right atrium, and right ventricle.

A patent foramen ovale is the most common remnant of the fetal circulation (see Figure 15-46C); it occurs in 10% to 15% of healthy adults and in 20% to 30% of normal hearts at postmortem.^10,56,90 The patent foramen varies in anatomic and functional size and is implicated in paradoxical embolization, transient ischemic attacks, venoarterial gas embolism, decompression sickness, and platypnea-orthodeoxia (see previous).^56,91

Atrial septal aneurysm is characterized by protrusion beyond the plane of the atrial septum and by rapid, dramatic phasic cardiorespiratory oscillations (see Figure 15-47 and Videos 15-4A through 15-4C).^11,12,92 An atrial septal defect may coexist. Cerebral emboli originate from fibrin-platelet aggregates on the left atrial side of the aneurysm and are dislodged by the phasic excursions.⁹² Atrial septal aneurysms have been incriminated in atrial arrhythmias in children and adults and in the fetus.

Physical Appearance

Children with an atrial septal defect may have a delicate gracile habitus, with weight more affected than height (Figure 15-14A), and may have a left precordial bulge with Harrison’s grooves (Figure 15-14B).⁹³ Newborns subsequently found to have an atrial septal defect are on average smaller than their healthy siblings.⁹⁴ Symptomatic infants may be cyanotic because of the effects of congestive heart failure. Cyanosis also occurs when a large eustachian valve (see previous) selectively channels inferior vena caval blood into the left atrium through an ostium secundum atrial septal defect (see Figure 15-4) or through an inferior vena caval sinus venosus defect (see Figure 15-48).^22,63,64

Figure 15-14 A, Five-year-old boy with a nonrestrictive ostium secundum atrial septal defect and a delicate, gracile appearance, with weight more affected than height. Harrison’s grooves caused by chronic dyspnea are identified by the arrows. B, Six-year-old girl with a nonrestrictive ostium secundum atrial septal defect and Harrison’s grooves (paired arrowheads).

The distinctive physical appearance of the Holt-Oram syndrome heightens suspicion of a coexisting ostium secundum atrial septal defect (Figure 15-15),^70,95,96 less commonly of an ostium primum defect. The thumb is hypoplastic with an accessory phalanx that results in triphalangism, a crooked appearance, and difficulty in apposition of thumb to fingertips. The abnormality becomes more obvious when the palms are supinated (see Figure 15-15B). The thumb may be rudimentary or absent, and the metacarpal bone may be small or absent with hypoplasia extending to the radius (Figure 15-16). The bony anomaly ranges from minor changes identified on x-ray to absence of the arm (abrachia) or absent arms with persistent underdeveloped hands (phocomelia).⁹⁷ Other cardiac malformations occur without prevailing patterns.⁷⁰ Mutations in a gene on chromosome 12q2 play an important role in skeletal and cardiac development and produce a wide range of partial phenotypes of the Holt-Oram syndrome.⁹⁸

Figure 15-15 A 34-year-old woman with Holt-Oram syndrome and an ostium secundum atrial septal defect. A, The left thumb is hypoplastic, and the left arm is shorter than the right. B, Radial hypoplasia prevented supination, but the crooked hypoplastic triphalangeal thumb became apparent. Fingertips of the supinated right hand are erythematous because of a small right-to-left shunt.

Figure 15-16 Photograph from a 26-year-old woman with Holt-Oram syndrome and absent thumb. An ostium secundum atrial septal defect coexisted.

Patau’s syndrome (trisomy 13) is characterized by polydactyly, flexion deformities of the fingers, palmar crease, microcephaly, holoproscencephaly, cleft lip, cleft palate, and low-set malformed ears. Edward’s syndrome (trisomy 18) is characterized by clenched fists, rocker bottom feet, prominent occiput, low-set malformed ears, and micrognathia (see Figures 19-5 and 20-11). The most common congenital cardiac malformations in trisomy 13 and in trisomy 18 are atrial septal defect, ventricular septal defect, and patent ductus arteriosus.⁹⁹ An atrial septal defect is associated with the Axenfeld-Rieger anomaly, a genetically heterogeneous autosomal dominant disorder characterized by ocular abnormalities with glaucoma and nonocular abnormalities that include maxillary hypoplasia, dental anomalies, umbilical hernia, and hypospadias.⁷⁵

Arterial Pulse

The arterial pulse is normal even though left ventricular ejection fraction tends to be decreased. Left ventricular output is maintained during the Valsalva’s maneuver despite a fall in systemic venous return because of the large volume of blood pooled in the lungs. Tachycardia is less pronounced during the straining phase, and there is a smaller decrease in pulse pressure. Bradycardia less is pronounced after cessation of straining, and the systolic overshoot is smaller. These abnormal responses can be identified with palpation of the brachial arterial pulse.

Jugular Venous Pulse

Most important is left atrialization of the jugular venous wave form.¹⁰⁰ The crests of the A and V waves tend to be equal as they are in the left atrium (Figure 15-17) because the two atria are in common communication through a nonrestrictive atrial septal defect. The A wave amplitude varies with heart rate as in healthy subjects.¹⁰¹ When left ventricular compliance decreases, left atrial pressure rises, and with it, the right atrial pressure.^100,101 Pulmonary vascular disease results in an increased force of right atrial contraction and a dominant, if not giant, A wave (Figure 15-18).

Figure 15-17 Sequential pressure pulses recorded as a catheter was withdrawn from right atrium (RA) to left atrium (LA) of an 11-year-old girl with a nonrestrictive ostium secundum atrial septal defect. The crests of A wave and V waves in the right and left atrium are identical because the atrial septal defect was nonrestrictive.

Figure 15-18 Pressure pulses from a cyanotic 34-year-old man with a nonrestrictive ostium secundum atrial septal defect and pulmonary vascular disease. Giant A waves in the right atrium (RA; first panel) were transmitted into the right ventricle (RV) as presystolic distention (second panel, arrows). Elevated right ventricular systolic pressure is shown in the third panel. (BA = brachial artery.)

Precordial Movement and Palpation

In 1934, Roesler⁵ called attention to the conspicuous thrust of the right ventricle in atrial septal defect. The impulse is hyperdynamic but not sustained because the volume-overloaded right ventricle contracts vigorously and empties rapidly into a low-resistance pulmonary vascular bed.^102,103 The impulse is especially prominent at the left sternal border during held exhalation and in the subxyphoid area during held inspiration.¹⁰³ Anterior movement at the left sternal border is accompanied by retraction at the apex because the enlarged right ventricle occupies the apex.^6,103 A dilated pulsatile pulmonary trunk is palpable in the second left intercostal space, but a systolic thrill is seldom present despite hyperkinetic right ventricular ejection into a dilated pulmonary trunk.

Auscultation

Auscultatory signs are the same in all varieties of isolated nonrestrictive atrial septal defects.^104–106 The first heart sound is split at the lower left sternal edge and apex, and the tricuspid component is loud (Figure 15-19).^103,105,107 Increased diastolic flow across the tricuspid valve depresses the bellies of the leaflets into the right ventricle, and vigorous right ventricular contraction causes abrupt cephalad excursion of the leaflets, generating a loud tricuspid component of the first heart sound.^104,107,108 A pulmonary ejection sound is uncommon, despite dilation of the pulmonary trunk (Figure 15-20).^106,109

Figure 15-19 Phonocardiogram from a 13-year-old girl with a nonrestrictive ostium secundum atrial septal defect and a 2.5 to 1 left-to-right shunt. The loud second component of the split first heart sound (T₁) is tricuspid and maximal at the lower left sternal edge (LSE). (M₁ = mitral component.) A soft pulmonary midsystolic murmur (SM) in the second left intercostal space (2 ICS) is followed by wide fixed splitting of the second heart sound. (A₂ = aortic component; P₂ = pulmonary component.)

Figure 15-20 Phonocardiograms from a 26-year-old woman before and after surgical closure of a nonrestrictive ostium secundum atrial septal defect. Before surgery, a grade 3/6 midsystolic pulmonary flow murmur (SM) was followed by wide fixed splitting of the second heart sound. (A₂ = aortic component; P₂ = pulmonary component.) After surgery, the pulmonary systolic murmur virtually disappeared, and the second sound split normally. A pulmonary ejection sound (E) was recorded in the postoperative tracing.

The pulmonary midsystolic flow murmur begins immediately after the first heart sound because right ventricular isovolumetric contraction is short. The murmur is grade 2/6 or 3/6, is maximal in the second left intercostal space over the pulmonary trunk, is impure and superficial because of proximity of the dilated pulmonary trunk to the chest wall, and is crescendo-decrescendo, peaking in early or mid systole and ending well before the second heart sound (Figures 15-21 and 15-22).^6,93,104,105 Origin in the pulmonary trunk has been confirmed with intracardiac phonocardiography (see Figure 15-22)¹⁰⁴ and with phonocardiograms recorded from the surface of the pulmonary trunk during surgery. The murmur radiates to the apex because the right ventricle occupies the apex.¹⁰⁵ A louder murmur is reserved for coexisting pulmonary valve stenosis. Systolic murmurs widely distributed in the right chest, axillae, and back are generated by rapid flow through peripheral pulmonary arteries (see Figure 15-21).^110,111

Figure 15-21 Phonocardiograms from a 21-year-old man with a nonrestrictive ostium secundum atrial septal defect. A grade 3/6 pulmonary midsystolic murmur (SM) in the second left intercostal space (2 LICS) is followed by wide splitting of second heart sound. (A₂ = aortic component; P₂ = pulmonary component.) Prominent systolic murmurs in the left axilla, right axilla, and right back were the result of rapid flow through peripheral pulmonary arteries. (S₁ = first heart sound.)

Figure 15-22 Intracardiac phonocardiograms from a 14-year-old boy with a nonrestrictive ostium secundum atrial septal defect and a 2.7 to 1 left-to-right shunt. A short midsystolic flow murmur (SM) was recorded in the main pulmonary artery (PUL ART). In the right ventricular outflow tract (RV), an early diastolic murmur of pulmonary regurgitation (EDM) was recorded despite normal pulmonary arterial pressure.

The pulmonary component of the second sound is prominent because of proximity of the dilated pulmonary trunk to the chest wall and because of brisk elastic recoil (Figure 15-23).¹⁰⁵ Wide fixed splitting is an auscultatory hallmark of atrial septal defect.^105,112,113 The aortic and pulmonary components are widely split during expiration, and the degree of splitting does not change during inspiration (Figures 15-20, 15-21, and 15-24) or during the Valsalva’s maneuver (Figure 15-25). Wide splitting is caused by a delay in the pulmonary component associated with an increase in pulmonary vascular capacitance and an increase in “hangout interval” between the descending limbs of the pulmonary arterial and right ventricular pressure pulses.^114–117 With a rise in pulmonary arterial pressure, the hangout interval decreases. The split then becomes a function of the relative duration of right and left ventricular electromechanical systole, which is the same in both ventricles because a potential increase in duration of right ventricular systole from volume overload is countered by accelerated ejection.¹¹⁶ A healthy child examined in the supine position may exhibit relatively wide but not fixed splitting of the second heart sound, but in the sitting position, respiratory splitting is normal.^103,118 The duration of diastole affects the degree of splitting by influencing the relative volumes of the right and left ventricles.¹¹⁹ As diastole shortens, the split narrows, and as diastole lengthens, the split widens,¹¹⁹ patterns that are evident in the beat-to-beat variations in cycle length with atrial fibrillation in which splitting tends to vary inversely with the duration of the preceding diastole.

Figure 15-23 Intracardiac phonocardiogram from an 8-year-old girl with a nonrestrictive ostium secundum atrial septal defect and 3 to 1 left-to-right shunt. In the inflow tract of the right ventricle, just distal to the tricuspid valve, the microphone recorded a mid-diastolic flow murmur (DM) and a loud tricuspid component of the first heart sound (T). (S₂ = second heart sound; RV = right ventricle.)

Figure 15-24 Tracings from a 28-year-old woman with a nonrestrictive ostium secundum atrial septal defect and a 2.3 to 1 left-to-right shunt. A, The grade 2/6 pulmonary midsystolic murmur (SM) is followed by wide splitting of the second heart sound. The pulmonary component (P₂) coincides with the dicrotic notch of the pulmonary artery pressure pulse (DN). B, The aortic component of the second sound (A₂) coincides with the dicrotic notch (DN) of the carotid pulse (CAR).

Figure 15-25 Phonocardiogram in the second left interspace during and after Valsalva’s maneuver in a 17-year-old girl with a nonrestrictive ostium secundum atrial septal defect. Splitting of the second heart sound remained wide and fixed. (S₁ = first heart sound; SM = pulmonary midsystolic murmur.)

Fixed splitting means that the width of the split remains constant throughout active respiration and during the Valsalva’s maneuver. Persistent splitting means that the split widens during inspiration and narrows during expiration. Atrial septal defect is characterized by splitting of the second heart sound that is wide and fixed (see Figure 15-20). During inspiration, the aortic and pulmonary components are equally delayed or do not move at all.¹²⁰ In the normal heart, inspiratory splitting is chiefly the result of a delay in the pulmonary component of the second sound because the increase in pulmonary capacitance during inspiration is accompanied by an increase in the hangout interval (Figure 15-26). The high pulmonary capacitance in atrial septal defect precludes an additional increase during inspiration, so there is no inspiratory delay in the pulmonary component of the second sound. Normal phasic changes in systemic venous return during respiration are associated with reciprocal changes in volume of the left-to-right shunt, which minimize the respiratory variations in right and left ventricular filling.^112,113,121 Inspiration is accompanied by an increase in systemic venous return, so right ventricular filling is maintained or increased while the left-to-right shunt decreases reciprocally; thus, left ventricular filling is maintained or is increased by the same amount. An inspiratory decrease in left-to-right shunt has been shown in experimental animals¹¹² and in human subjects.¹²² Wide fixed splitting is unlikely in neonates because there is little or no shunt in either direction.¹²³

Figure 15-26 Respiratory behavior of the second heart sound in the normal heart and in the presence a nonrestrictive atrial septal defect with a left-to-right shunt. Normal inspiratory splitting (Insp.) is chiefly the result of a delay in the pulmonary component (P₂), less the result of movement of the aortic component (A₂) in the opposite direction. In an atrial septal defect, the second sound is widely split during expiration (Exp.) because the pulmonary component (P₂) is late. The split remains fixed during active inspiration and expiration because both components move equally and in the same direction, or do not move at all. (SM = systolic murmur.)

These patterns of splitting do not apply when partial anomalous pulmonary venous connection occurs with an intact atrial septum (Figure 15-27).^113,124 Increased venous return during inspiration is not accompanied by a reciprocal fall in left-to-right shunt because the atrial septum is intact. Accordingly, the aortic component of the second heart sound moves toward the first heart sound and the pulmonary component moves away, so the split widens with inspiration and narrows with expiration (see Figure 15-27).

Figure 15-27 Phonocardiograms and carotid pulse (CAR) from a 16-year-old girl with anomalous pulmonary venous connection of the entire right lung to the inferior vena cava and an intact atrial septum (see Figure 15-9). The second heart sound is persistently split, but the split is not fixed. (A₂ = aortic component; P₂ = pulmonary component; SM = systolic murmur; 2 LSE = second intercostal space left sternal edge; Insp./Exp. = inspiration and expiration.)

Rarely, an opening sound of the tricuspid valve follows the pulmonary component of the second heart sound.^105,107 Echocardiographic timing confirms that the sound coincides with abrupt arrest of the opening movement of the tricuspid valve in early diastole.¹⁰⁷ Mid-diastolic murmurs are the result of augmented tricuspid flow.^{104,105,125,126} Origin of the flow murmur at the tricuspid orifice has been shown experimentally in animals and with intracardiac phonocardiography in human subjects (Figure 15-28).^104,127 Tricuspid flow murmurs are medium frequency, impure, soft, short, presystolic or mid-diastolic, and localized at the lower left sternal border and do not increase with inspiration despite their right-sided origin. Intracardiac phonocardiograms identify low-intensity inaudible diastolic murmurs within the atrial septal defect itself.^125–127 The combination of superficial impure presystolic and mid-diastolic murmurs together with a superficial impure midsystolic murmur occasionally creates the impression of a pericardial rub. Occasionally, a rub in fact does occur, and attention has been called to roughened pericardium in patients with an atrial septal defect (Figure 15-29).^128,129 A diastolic murmur of low-pressure pulmonary regurgitation is uncommon (see Figure 15-22) and is reserved for aneurysmal dilation of the pulmonary trunk.¹³⁰ Continuous murmurs through restrictive atrial septal defects are rare.¹³¹ Atrial septal defects with pulmonary vascular disease and reversed shunts are accompanied by auscultatory signs of pulmonary hypertension (Figures 15-30 and 15-31; see Chapter 14).^105,132,133

Figure 15-28 Tracings from a 4-year-old boy with a nonrestrictive ostium secundum atrial septal defect and a 2.3 to 1 left-to-right shunt. A, The pulmonary component (P₂) of the split second sound is loud even though the pulmonary arterial pressure was normal as shown in panel. B, (S₁ = first heart sound; A₂ = aortic component of the second sound; SM = systolic murmur; FA = femoral artery pulse; PA = pulmonary artery pulse.)

Figure 15-29 A, Lateral x-ray from a 65-year-old man with a nonrestrictive ostium secundum atrial septal defect and large pericardial and pleural effusions. B, The effusions were benign transudates that decreased appreciably after pericardiocentesis. Thickened pericardium was identified at surgery for closure of the atrial septal defect.

Figure 15-30 Tracings from a 28-year-old cyanotic woman with a nonrestrictive ostium secundum atrial septal defect and pulmonary vascular disease. A pulmonary ejection sound (E) introduced a soft short midsystolic murmur (SM) in the second left intercostal space (2 LICS). The second heart sound (S₂) is loud and single and introduced a decrescendo Graham Steell murmur (DM). (S₁ = first heart sound; 4 LICS = fourth left intercostal space; CAR = carotid pulse.)

Figure 15-31 Tracings from a 32-year-old woman with a nonrestrictive ostium secundum atrial septal defect, pulmonary vascular disease, a 1.4 to 1 left-to-right shunt, and a small right-to-left shunt. Pulmonary artery systolic pressure was 90 mm Hg, and systemic systolic pressure was 110 mm Hg. A, The first heart sound (S₁) is followed by a prominent pulmonary ejection sound (E). (2 LICS = second left intercostal space.) The second heart sound remained split. The loud pulmonary component (P₂) was transmitted to the apex. (A₂ = aortic component.) B, The ejection sound and the loud pulmonary component of the second sound transmitted to the third left intercostal space (3 LICS). A prominent fourth heart sound (S₄) was present at the lower left sternal border.

Electrocardiogram

Sinus node dysfunction has been identified as early as age 2 to 3 years,^134–136 and accelerated atrial rhythms have been recorded on 24-hour ambulatory electrocardiograms in 35% of children with an atrial septal defect.¹³⁴ The incidence of atrial fibrillation, atrial flutter, and supraventricular tachycardia increases in the fourth decade (Figures 15-32 and 15-33).^89,136 Interestingly, sinus arrhythmia does not occur in adults with an atrial septal defect and is minimal or absent in children (see Figure 15-33). Sinus arrhythmia requires separation of the systemic and pulmonary venous returns. With an atrial septal defect, the two venous returns are by definition not separated.¹³⁷

Figure 15-32 Electrocardiogram from an acyanotic man with a nonrestrictive ostium secundum atrial septal defect who died 3 months before his 95th birthday. The rhythm was atrial fibrillation. Left axis deviation was the result of acquired left anterior fascicular block. The right ventricular conduction defect was peripheral, not central.

Figure 15-33 A, Leads 3, aVF, and V₃ from a 60-year-old woman with an ostium secundum atrial septal defect and a 2.6 to 1 left-to-right shunt. The rhythm is atrial flutter (paired arrows) with an irregular ventricular response. B, The upper rhythm strip (lead 2) illustrates absence of sinus arrhythmia in a 19-year-old woman with a nonrestrictive ostium secundum atrial septal defect. The lower rhythm strip illustrates typical sinus arrhythmia that appeared after surgical closure of the atrial septal defect. The rsr prime in lead V₁ remained unchanged.

Atrioventricular conduction defects are intrinsic components of atrial septal defects and are usually age related.^134,136,138 The PR interval tends to be prolonged.¹³⁹ Atrioventricular node dysfunction begins in older children and is less frequent than sinus node dysfunction.^135,136 Advanced first-degree atrioventricular nodal block occurs with familial or, less commonly, nonfamilial atrial septal defect and occasionally culminates in complete heart block.^71–74 Some family members have an ostium secundum atrial septal defect and first-degree heart block, and others have PR prolongation with an intact atrial septum.⁷¹ In the Holt-Oram syndrome (see Figures 15-15 and 15-16), PR interval prolongation, sinus bradycardia, and ectopic atrial rhythms are relatively common.⁷⁰

Abnormal right atrial P waves are peaked rather than tall (Figure 15-34), but P wave configurations are usually normal (Figure 15-35).¹⁴⁰ Prolonged P wave duration occurs when the terminal force is written by an enlarged right atrium.^141–143 The P wave axis with an ostium secundum atrial septal defect is inferior and to the left with upright P waves in leads 2, 3, and aVF (see Figures 15-34 and 35). With a superior vena vaval sinus venosus atrial septal defect, the atrial pacemaker is ectopic because the defect occupies the site of the sinoatrial node. The P wave axis is then leftward, and the P waves are inverted in leads 2, 3, and aVF and upright in lead aVL (Figure 15-36). Superior vana caval sinus venosus defects are occasionally accompanied by shifts from sinus rhythm with a normal P axis to an ectopic atrial rhythm with a leftward P axis.

Figure 15-34 Electrocardiogram from a 5-year-old boy with a nonrestrictive ostium secundum atrial septal defect and a 3.5 to 1 shunt. P waves are peaked and tall in lead 2 and V₃R and in leads V_1–2. The QRS axis is vertical. Depolarization is clockwise, so Q waves appear in leads 2, 3, and aVF. There is an rsR prime pattern in leads V₁ and V₃R.

Figure 15-35 Electrocardiogram from a 24-year-old woman with a nonrestrictive ostium secundum atrial septal defect and a 2 to 1 left-to-right shunt. P waves are normal. The QRS axis is vertical with clockwise depolarization and Q waves in leads 2, 3, and aVF. The terminal QRS forces are directed upward, to the right and anterior, and are slightly prolonged, so an rSr prime appears in lead V₁, a slurred terminal R wave appears in lead aVR, and slurred S waves appear in left precordial leads.

Figure 15-36 Electrocardiogram from a 25-year-old woman with a superior vena caval sinus venosus atrial septal defect. The P wave axis is leftward and markedly superior, so P waves are inverted in leads 2, 3, and aVF; are isoelectric in lead 1; and are slightly positive in lead aVR. Intracardiac electrophysiologic investigation identified an ectopic left atrial pacemaker. The QRS pattern is typical of a left-to-right shunt at atrial level, namely, a vertical QRS axis and prolonged terminal forces directed to the right, superior and anterior, with an rSR prime in lead V₁ and S waves in left precordial leads.

The QRS duration is slightly prolonged in atrial septal defects because of slurring of the terminal force (see Figure 15-35). The duration increases with age and may culminate in a pattern that resembles complete right bundle branch block (see Figure 15-32). The QRS axis is vertical with clockwise depolarization that writes q waves in leads 2, 3, and aVF (see Figures 15-34 and 15-35). Right axis deviation is reserved for infants with symptomatic pulmonary hypertension or for young females with pulmonary vascular disease. Left axis deviation is exceptional and represents acquired left anterior fascicular block in older adults (see Figure 15-32).¹⁴⁴

An electrocardiographic hallmark of atrial septal defect is an rSr prime or an rsR prime in right precordial leads (see Figures 15-34 and 15-35).^6,145,146 The r prime in lead V₁ and aVR is slurred in contrast to thin terminal r waves in 5% of normal electrocardiograms. Q waves are small or absent in left precordial leads because the shunt does not traverse the left ventricle (see Figures 15-34, 15-35, and 15-36). The outflow tract of the right ventricle is the last portion of the heart to depolarize. Enlargement and increased thickness caused by right ventricular volume overload are responsible for the rightward superior and anterior direction of the terminal force of the QRS and for increased QRS duration.^147–149 The term incomplete right bundle branch block is a misnomer.¹⁴⁹

A notch near the apex of the R waves in inferior leads of ostium secundum and sinus venosus atrial septal defects has been called crochetage¹⁵⁰ because the notch resembles the work of a crochet needle (Figure 15-37).¹⁵¹ Crochetage is independent of the terminal force direction of the QRS, but when the rSr prime pattern occurs with crochetage in each of the inferior limb leads, the specificity of the electrocardiographic diagnosis of atrial septal defect is remarkably high.¹⁵⁰ Although crochetage has been correlated with shunt severity, the pattern has also been reported with a patent foramen ovale and has been suggested as an electrocardiographic marker of a patent foramen.¹⁵²

Figure 15-37 Electrocardiogram from a 32-year-old woman with a nonrestrictive ostium secundum atrial septal defect and a 2.6 to1 left-to-right shunt. Crochetage is represented by notches on the R waves in leads 2, 3, and aVF.

X-Ray

Increased pulmonary arterial vascularity extends to the periphery of the lung fields (Figures 15-38 and 15-39). The pulmonary trunk and its proximal branches are dilated (see Figure 15-39). The left branch is usually obscured by an enlarged pulmonary trunk (see Figure 15-39), but the lateral view discloses dilation of both branches (Figures 15-39 and 15-40). The ascending aorta is seldom border forming because the intracardiac shunt does not traverse the aortic root (see Figures 15-38 and 15-39).^5,153 However, angiographic and echocardiographic assessments indicate that the intrinsic caliber of the ascending aorta is not significantly reduced. A sinus venosus atrial septal defect may be accompanied by localized ampullary dilation of the superior vena cava proximal to its attachment to the right atrium (Figure 15-41).¹⁵ Infants with large left-to-right shunts exhibit both pulmonary arterial and pulmonary venous vascularity with enlargement of all four cardiac chambers.¹²³ In older adults with moderate pulmonary hypertension and persistent left-to-right shunt, the pulmonary trunk and proximal branches are occasionally aneurysmal (Figure 15-42). In young adults with pulmonary vascular disease and a balanced or reversed shunt, the pulmonary trunk and its branches are strikingly enlarged and calcified (see Figures 15-11 and 15-13).

Figure 15-38 X-ray from a 5-year-old boy with a nonrestrictive ostium secundum atrial septal defect and a 2.5 to 1 left-to-right shunt. Pulmonary vascularity is increased and the pulmonary trunk and its right branch are prominent, but the ascending aorta is inconspicuous. The right atrium occupies the lower right cardiac border, and a dilated right ventricle occupies the apex.

Figure 15-39 X-rays from a 31-year-old woman with a nonrestrictive ostium secundum atrial septal defect and a 3.2 to 1 left-to-right shunt. The frontal projection shows increased pulmonary arterial vascularity that extends to the periphery of the lung fields (enhanced by breast tissue). The pulmonary trunk and its right branch are dilated in contrast to the non–border-forming ascending aorta. An enlarged right atrium occupies the lower right cardiac border, and an enlarged right ventricle occupies the apex. In the lateral projection, arrows bracket a dilated right pulmonary artery, which was obscured in the frontal projection by the dilated pulmonary trunk. The retrosternal space is obliterated by enlargement of the right atrium and right ventricle despite an increase in anteroposterior chest dimension caused by bowing of the sternum. In the barium esophagram, the left atrium is not enlarged.

Figure 15-40 Lateral x-ray from a 48-year-old man with a nonrestrictive ostium secundum atrial septal defect and a 2.5 to 1 left-to-right shunt. The end-on right pulmonary artery (RPA) is dilated, and the left pulmonary artery (LPA) appears as a large comma-like shadow. The right ventricle (RV) encroaches on the retrosternal space. The left atrium is not enlarged.

Figure 15-41 X-ray from a 26-year-old woman with a superior vena caval sinus venosus atral septal defect and a 2 to 1 left-to-right shunt. Arrows bracket subtle localized dilation of the superior vena cava as it joins the right atrium. The x-ray otherwise resembles an ostium secundum atrial septal defect of equilavent size.

Right atrial enlargement is characteristic (Figures 15-39A and 15-43), but the left atrium seldom enlarges despite a left-to-right shunt (see Figure 15-39B) because a major portion of pulmonary venous return enters the right atrium directly owing to the proximity of the right pulmonary veins to the rim of the ostium secundum atrial septal defect (see previous).^54,154 Left atrial enlargement is reserved for older adults with atrial fibrillation.^89,155 Volume elastic properties of the right and left atrium also play a role in determining relative enlargement. For equal increments in volume, the right atrium is more distensible than the left.¹⁵⁴

An enlarged right ventricle occupies the apex and forms an acute angle with the left hemidiaphragm (see Figure 15-38). Dilation of the outflow tract causes smooth continuity with the enlarged pulmonary trunk above (see Figure 15-38). In the lateral projection, the dilated right ventricle encroaches on the retrosternal space (see Figures 15-39B and 15-40), and displaces the left ventricle posteriorly. The size of the left ventricle is normal because its stroke volume is normal or reduced. The relationship between the inferior vena caval shadow and the left ventricular shadow in the lateral projection distinguishes posterior displacement of the left ventricle from intrinsic dilation (Figure 15-44).¹⁵⁶ The lateral projection in adults often shows disproportionate anterior bowing of the upper third of the sternum (see Figure 15-39B). A progressive and often dramatic increase in heart size is initiated by atrial tachyarrhythmias, especially atrial fibrillation with congestive heart failure (Figures 15-12 and 15-45).¹⁵⁵

Figure 15-44 A, The relationship of the inferior vena cava (IVC) and the posterior silhouette of an enlarged left ventricle (LV) when the right ventricle is normal. At the level of the diaphragm, the caval shadow lies within the left ventricular silhouette. B, The relationship of the inferior vena cava to the posterior silhouette of a normal left ventricle that is retrodisplaced by an enlarged right ventricle. At the level of the diaphragm, the caval shadow lies behind the left ventricle.

(Modified from Keats TE, Rudhe U, Foo GW. Inferior vena caval position in the differential diagnosis of atrial and ventricular septal defects. Radiology 83:616, 1964.)

In the scimitar syndrome, the confluence of right pulmonary veins forms a distinctive shadow parallel to or behind the right cardiac silhouette as the anomalous venous channels course downward to join the inferior vena cava (see Figures 15-8, 15-9, and 15-10).^28,37,157 The heart is displaced into the right hemithorax because of hypoplasia of the right lung, but the anomalous venous channels usually remain visible (see Figures 15-9 and 15-10).

Echocardiogram

Echocardiography with color flow imaging and Doppler interrogation establishes the location and size of an atrial septal defect and its physiologic consequences.²¹ Transesophageal echocardiography has refined the anatomic assessment of the interatrial septum^9,158 and identifies partial anomalous pulmonary venous connections.^62,159,160 Pulsed Doppler imaging can identify anomalous pulmonary venous connections in the fetus.¹⁶¹ Real-time three-dimensional transesophageal echocardiography has optimized assessment of atrial septal defects.¹⁶² An ostium secundum atrial septal defect is represented by an echo-free space in the mid portion of the atrial septum (see Figure 15-5A). Color flow imaging confirms that the echo-free space is a true tissue defect, and pulsed Doppler imaging characterizes instantaneous flow patterns across the defect (see Figure 15-5B). A foramen ovale can be identified (Figure 15-46C and Video 15-2C), and color flow determines its patency.^90,163 An in utero patent foramen can be distinguished from an ostium secundum atrial septal defect.²⁷ Transthoracic and transesophageal echocardiography establish the diagnosis of atrial septal aneurysm (Figure 15-47A and Video 15-4A), and color flow imaging or echocontrast determines whether an atrial septal defect coexists (Figure 15-47B and Video 15-4B).^12,164

Transesophageal echocardiography identifies a divided right atrium that consists of a shelf that separates an anterior supratricuspid component from a posterior systemic venous sinus, to which the cava are connected.¹⁶⁵ A rare double atrial septum is imaged as a midline chamber between the left and right atrium.¹⁶⁶

Real-time imaging discloses a dilated hyperkinetic right ventricle with paradoxical motion of the ventricular septum^51,167 and vigorous pulsations of the pulmonary trunk and its branches. The size, shape, and functional reserve of the left ventricle can be determined (see Figure 15-46B).^52,53

A superior vena caval sinus venosus defect lies near the junction of the superior cava and the right atrium (Figure 15-48A),^21,158 and an inferior vena caval sinus venosus defect lies just beyond the rim of the inferior vena cava.¹⁶³ An unroofed coronary sinus is identified by dilation of the sinus and by a defect between the sinus and left atrium.

Summary

Ostium secundum atrial septal defects predominate in females and often come to light in asymptomatic children or young adults. Patients usually reach their fourth decade with little or no handicap. Preadolescents sometimes appear delicate and gracile. Dyspnea, fatigue, and recurrent lower respiratory infections are common. The left-to-right shunt in older adults is augmented by ischemic heart disease, systemic hypertension, and acquired calcific aortic stenosis that decrease left ventricular compliance. Atrial tachyarrhythmias, especially atrial fibrillation, precipitate congestive heart failure. The crests of the jugular venous A and V waves are equal (left atrialization). The right ventricular impulse is hyperdynamic, and a systolic pulsation is palpated over the dilated pulmonary trunk. The first heart sound is split with a loud tricuspid component. A grade 2/6 or 3/6 pulmonary midsystolic murmur is followed by fixed splitting of the second heart sound and a tricuspid mid-diastolic flow murmur.

P waves are peaked but seldom tall. The QRS axis is vertical with clockwise depolarization and q waves in leads 2, 3, and aVF. Terminal forces of the QRS are prolonged and point to the right and anterior, producing an rSr prime in lead V₁. Notching of the R waves in inferior leads results in a distinctive crochetage pattern. The x-ray shows increased pulmonary arterial vascularity, an inconspicuous ascending aorta, dilation of the pulmonary trunk and its proximal branches, and enlargement of the right atrium and right ventricle. The scimitar syndrome is characterized by partial anomalous right pulmonary venous connection with infradiaphragmatic drainage and hypoplasia of the right lung. Echocardiography with color flow imaging and Doppler interrogation establishes the location and size of the atrial septal defect, its physiologic consequences, and the presence of partial anomalous pulmonary venous connections. A nonrestrictive ostium secundum atrial septal defect with pulmonary vascular disease is believed to represent the coexistence of primary pulmonary hypertension in young females.

A superior vena caval sinus venosus atrial septal defect is clinically similar to an equivalent ostium secundum defect with two exceptions: first, the atrial pacemaker is ectopic so the P wave axis is leftward and inverted P waves appear in leads 2, 3, and aVF; second, the right hilus may show localized ampullary dilatation of the distal superior vena cava as it joins the right atrium. Echocardiography confirms the location of the defect.

Ostium secundum atrial septal defects in the young are among the most readily diagnosed congenital malformations of the heart, but these same defects sometimes defy clinical recognition because of diagnostic ambiguities. The diagnosis of mitral stenosis is entertained (Box 15-1) because of dyspnea, orthopnea, atrial fibrillation, an increased jugular venous V wave, a right ventricular impulse, a loud first heart sound, a delayed pulmonary component of the second heart sound mistaken for an opening snap, a tricuspid flow murmur mistaken for a mitral diastolic murmur, shunt vascularity mistaken for pulmonary venous congestion, and dilation of the pulmonary trunk, the right atrium, and occasionally, the left atrium. Mitral regurgitation may be misdiagnosed as acquired (Box 15-2) because the holosystolic murmur of tricuspid regurgitation is well heard at the apex, a delayed pulmonary component of the second sound followed by a tricuspid flow murmur is mistaken for an opening snap and the mid-diastolic murmur of mitral stenosis, and a tricuspid flow murmur is mistakenly attributed to flow across the mitral valve. Diagnostic ambiguity in older adults results from atrial arrhythmias, ischemic heart disease, systemic hypertension, and inverted left precordial T waves (Box 15-3).

Symptomatic infants with a large left-to-right shunt through an ostium secundum atrial septal defect pose a diagnostic problem to clinicians who are not accustomed to considering an atrial septal defect in neonates. Splitting of the second heart sound is variable and difficult to assess, the pulmonary component is increased, and a holosystolic murmur of tricuspid regurgitation and a tricuspid diastolic flow murmur are misinterpreted. The diagnosis is established with echocardiography. These infants often experience spontaneous closure of the atrial septal defect.

History

Lutembacher’s syndrome has a predilection for females because ostium secundum atrial septal defect and rheumatic mitral stenosis are both more prevalent in females.^32,176 The incidence rate of mitral stenosis in patients with atrial septal defect has been estimated at 4%.^32,176 The incidence rate of atrial septal defect in patients with mitral stenosis has been estimated at 0.6% to 0.7%.^32,176 Mitral stenosis is rheumatic even when Lutembacher’s syndrome is familial because it is the atrial septal defect that is genetically transmitted. The incidence rate of coexisting rheumatic mitral stenosis depends on the geographic prevalence of rheumatic fever.¹⁷⁶ In underdeveloped countries, a history of rheumatic fever has been reported in 40% of patients with Lutembacher’s syndrome.¹⁷⁶

The most important clinical consequence of a nonrestrictive atrial septal defect in Lutembacher’s syndrome is its ameliorating effect on the symptoms of mitral stenosis. Orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema, and hemoptysis are infrequent and attenuated and replaced by fatigue from reduced left ventricular filling and low cardiac output.¹⁷¹ When mitral stenosis is severe and the atrial septal defect restrictive, the symptoms and clinical course resemble isolated mitral stenosis of equivalent severity.^32,176

The ameliorating effects of an atrial septal defect were evident in Lutembacher’s original patient, a 61-year-old woman who had had seven pregnancies.¹⁶⁹ Firkett’s patient was a 74-year-old woman who experienced 11 pregnancies.¹⁸⁰ An 81-year-old woman had no cardiac symptoms until her 75th year,¹⁸² and survival to advanced age has been reaffirmed.^172,183,184 However, these reports should not discount the unfavorable long-term effect exerted by an atrial septal defect on mitral stenosis that increases the left-to-right shunt and predisposes to atrial fibrillation.^172,176 Susceptibility to infective endocarditis resides in the stenotic mitral valve in contrast to negligible susceptibility in an uncomplicated ostium secundum atrial septal defect.

Arterial Pulse

The arterial pulse is small because left ventricular stroke volume is small. Atrial fibrillation reduces the pulse still further (Figure 15-50).¹⁷⁶

Figure 15-50 Tracings from a 42-year-old woman with Lutembacher’s syndrome that consisted of rheumatic mitral stenosis and a nonrestrictive superior vena caval sinus venosus atrial septal defect with a left-to-right shunt of 2.5 to 1, a mitral orifice of 1.1 cm², and pulmonary artery pressure of 38/18 mm Hg. The carotid pulse (CAR) was small because left ventricular stroke volume was reduced by atrial fibrillation shown in the rhythm strip below. Phonocardiogram at the apex recorded a prominent first heart sound (S₁), wide splitting of the second heart sound (A₂ = aortic component; P₂ = pulmonary component), an opening snap (OS), and a middiastolic murmur (MDM). The pulmonary component of the second sound was transmitted to the apex, which was occupied by the right ventricle. In the second left intercostal space (2 LICS), the phonocardiogram shows a soft pulmonary midsystolic murmur (SM) and wide splitting of the second heart sound followed by an opening snap (OS). (4 LICS = fourth left intercostal space.)

Jugular Venous Pulse

The right and left atrium function as a common chamber when the atrial septal defect is nonrestrictive, so the height and contour of the left atrial pressure pulse are transmitted into the right atrium and into the internal jugular vein. Lutembacher’s syndrome is therefore responsible for an elevated mean jugular venous pressure in the absence of right ventricular failure and for an elevated jugular venous A wave in the absence of pulmonary hypertension.

Precordial Movement and Palpation

The impulse of the right ventricle and pulmonary trunk are more prominent in Lutembacher’s syndrome with a nonrestrictive atrial septal defect than with an uncomplicated atrial septal defect of the same size because mitral stenosis augments the left-to-right shunt. The underfilled left ventricle cannot be palpated. The diastolic thrill of mitral stenosis is exceptional because the velocity of mitral valve flow is comparatively low.

Auscultation

The auscultatory signs of mitral stenosis are attenuated on two counts (see Figure 15-50).³² First, flow across the stenotic mitral valve is reduced because left atrial blood has an alternative exit across the atrial septal defect, an explanation correctly proposed by Lutembacher to account for the atypical characteristics of the mitral diastolic murmur.¹⁶⁹ Second, the auscultatory signs of uncomplicated mitral stenosis are heard best over the left ventricular impulse¹⁰³; but in Lutembacher’s syndrome, the cardiac apex is occupied by the volume-overloaded right ventricle, so a topographic auscultatory advantage is lost.

When a nonrestrictive atrial septal defect occurs with mild mitral stenosis, the auscultatory signs resemble those of the atrial septal defect.³² The diagnostic yield is improved when the patient turns into a left lateral decubitus position and coughs briskly, while the bell of the stethoscope is applied to the approximate location of the apex.¹⁰³ Mitral stenosis increases the left-to-right shunt and augments the midsystolic flow murmur across the pulmonary valve. Right ventricular dilation is accompanied by the holosystolic murmur of tricuspid regurgitation that transmits to the apex, inviting a mistaken diagnosis of mitral regurgitation.¹⁷⁶ Inspiratory augmentation of the tricuspid murmur—Carvallo’s sign—should prevent error. When the atrial septal defect is restrictive, mitral stenosis results in a continuous gradient from left atrium to right atrium and a continuous murmur at the lower right sternal border because the murmur is generated within the right atrial cavity.^178,179 The continuous murmur may increase with slow deep inspiration because of a delayed inspiratory increase in left atrial volume.¹⁷⁹ During the straining phase of the Valsalva’s maneuver, the interatrial gradient is reduced or abolished, and the continuous murmur diminishes.¹⁷⁹

Electrocardiogram

When the atrial septal defect is restrictive, the electrocardiogram resembles that of mitral stenosis. When the atrial septal defect is nonrestrictive, the electrocardiogram resembles that of an atrial septal defect. P waves show left atrial abnormalities with a broad bifid configuration in lead 2 and a deep prolonged P terminal force in lead V₁ (Figure 15-51).^32,185 However, atrial fibrillation is frequent. Right ventricular hypertrophy is more common than with isolated atrial septal defect.

Figure 15-51 Electrocardiogram from the 42-year-old woman with Lutembacher’s syndrome. The phonocardiogram is shown in Figure 15-50. There are broad notched left atrial P waves in leads 2 and aVL, with a broad deep left atrial P terminal force in leads V_1-2. The leftward P wave axis with inverted P waves in leads 3 and aVF was the result of an ectopic atrial pacemaker associated with a superior vena caval sinus venosus atrial septal defect. The QRS pattern resembles an ostium secundum defect with a prolonged terminal force directed to the right, superior, and anterior (rsr prime in lead V₁, a qr in aVR, and a broad S wave in lead V₆). The rhythm strip below shows atrial fibrillation.

X-Ray

A restrictive atrial septal defect results in an x-ray that resembles mitral stenosis with pulmonary venous congestion and left atrial enlargement. When the atrial septal defect is nonrestrictive, the x-ray shows increased pulmonary arterial blood flow but little or no pulmonary venous congestion because the left atrium is decompressed (Figure 15-52). Left atrial enlargement is less than expected for equivalent mitral stenosis but more than expected for an uncomplicated atrial septal defect (see Figure 15-52B).^176,185 Left atrial size increases with the advent of atrial fibrillation.¹⁷⁶ Dilation of the right atrium, right ventricle, and pulmonary trunk exceeds expectations for an uncomplicated atrial septal defect. Whether mitral valve calcification is infrequent or simply overlooked is unclear.

Figure 15-52 X-rays from the 42-year-old woman with Lutembacher’s syndrome (see Figures 15-50 and 15-51). A, The frontal projection shows no signs of pulmonary venous congestion. The pulmonary trunk is moderately prominent and merges with the shadow of the left atrial appendage, resulting in a straight left cardiac border. The ascending aorta is not border-forming. An enlarged right atrium occupies the lower right cardiac border, and an enlarged right ventricle occupies the apex. B, The right anterior oblique projection shows retrodisplacement of the barium esophagram by a moderately enlarged left atrium (paired arrows).

Echocardiogram

Echocardiography with color flow imaging and Doppler interrogation is used to establish the diagnosis of Lutembacher’s syndrome, identify the location and size of the atrial septal defect, and determine the degree of mitral stenosis (see Figure 15-49).^178,186 A continuous murmur at the right lower sternal border coincides with Doppler flow patterns recorded with transesophageal echocardiography in the presence of a restrictive atrial septal defect.¹⁷⁸

Summary

Lutembacher’s syndrome has a predilection for females because ostium secundum atrial septal defect and rheumatic mitral stenosis are both prevalent in females.* Despite the rheumatic etiology of mitral stenosis, a history of active rheumatic fever in childhood is obtained in less than half the cases.

When the atrial septal defect is restrictive, the clinical picture resembles isolated mitral stenosis. A continuous murmur at the right sternal border is generated within the right atrial cavity. The electrocardiogram shows left atrial P wave abnormalities, and the x-ray shows pulmonary venous congestion and left atrial enlargement.

When the atrial septal defect is nonrestrictive, the effects of mitral stenosis are attenuated because the left atrium is decompressed, while mitral stenosis augments the left-to-right interatrial shunt. The arterial pulse is small, especially with the advent of atrial fibrillation. The jugular venous pulse exhibits a prominent A wave in the absence of pulmonary hypertension because the left atrial pressure pulse is transmitted into the right atrium through the nonrestrictive atrial septal defect. Auscultatory signs of mitral stenosis are blunted or absent. A pulmonary midsystolic flow murmur is evident because right ventricular stroke volume is increased. The electrocardiogram in sinus rhythm shows left atrial P wave abnormalities. Right ventricular hypertrophy is more common than with an uncomplicated atrial septal defect. The x-ray shows increased pulmonary arterial blood flow with little or no pulmonary venous congestion. The right atrium, right ventricle, and pulmonary trunk are considerably enlarged. Echocardiography with color flow imaging and Doppler interrogation establishes the presence and severity of mitral stenosis, the location and size of the atrial septal defect, and the physiologic consequences of the combination. Mitral stenosis is a substrate for infective endocarditis.

History

Symptoms begin earlier and are more pronounced than with a nonrestrictive atrial septal defect.¹⁸⁷ Most patients experience dyspnea, fatigue, respiratory infections, mild cyanosis, and physical underdevelopment in the first year of life. Occasional patients are relatively well into late childhood or early adolescence^187,191 but are rarely into adulthood (see Figure 15-54).

Physical Appearance

Cyanosis occurs despite insufficient evidence of pulmonary hypertension to account for its presence and may be insignificant at rest but induced by exercise or crying. Small or intermittent right-to-left shunts express themselves as highly colored cheeks or digital erythema. The Down phenotype is not a feature of common atrium, despite the presence of elements of an atrioventricular septal defect. However, the Ellis-van Creveld syndrome, chondroectodermal dysplasia, is an important phenotype because 50% of patients with this syndrome have congenital heart disease and half of them have a common atrium.^192–194 Ellis-van Creveld syndrome is autosomal recessive and is characterized by dwarfism with polydactyly of the hands that is invariable (Figures 15-55A), but polydactyly of the feet occurs in only 10% of cases (Figure 15-55B).¹⁹⁴ Polycarpaly (a ninth or tenth carpal bone), clinodactyly (bent fingers), syndactyly (interdigital webbing), and hypoplasia of the nails^194,195 are common features (Figures 15-55 and 15-56). Premature eruption of malformed maxillary incisors, gingival hypertrophy, and multiple frenula are distinctive (Figure 15-57).

Figure 15-55 Photographs from a female neonate with Ellis-van Creveld syndrome and common atrium. A, The hand is characterized by a well-formed extra digit on its ulnar aspect (polydactyly), clinodactyly (bent fingers), and syndactyly (interdigital webbing). Hypoplasia of the nails is better seen in the foot (B) and in Figure 15-56.

Figure 15-56 Close-up view of the fingers of a 53-year-old woman with dwarfism with Ellis-van Creveld syndrome and hypoplasic nails (arrows).

(From Hearst JW. The heart. 4th ed. New York: McGraw-Hill Book Company; 1978, with permission.)

Figure 15-57 Female neonate with Ellis-van Creveld syndrome, premature eruption of malformed maxillary incisors, gingival hypertrophy, and multiple frenula.

Arterial Pulse, Jugular Venous Pulse, Precordial Movement and Palpation, and Auscultation

The arterial pulse, the jugular venous pulse, and precordial palpation are analagous to a nonrestrictive ostium secundum atrial septal defect (see previous). Auscultatory signs are also similar, with the important exception of an apical holosystolic murmur of mitral regurgitation caused by the malformed left atrioventricular valve (see Figure 15-54B). An increase in the jugular A wave and a loud pulmonary component of the second heart sound reflect the early development of pulmonary hypertension.

Electrocardiogram

Absence of the atrial septum assumes deficiency of the superior vena caval sinus venosus location, the ostium primum or atrioventricular septal location, and the ostium secundum location. The electrocardiogram reflects the deficiencies at all of these sites.¹⁸⁸ Leftward deviation of the P wave axis with inverted P waves in the inferior leads is analogous to the ectopic atrial pacemaker in a superior vena caval sinus venous atrial septal defect with an absent sinus node.^188,187,196 Left axis deviation of the QRS with counterclockwise depolarization (Figures 15-58 and 15-59) and splintering of S waves in the inferior leads (see Figure 15-59) is analogous to the electrocardiogram of an atrioventricular septal defect.^21,187,188 The precordial leads are analogous to an ostium secundum atrial septal defect, but early development of pulmonary hypertension results in increased R wave amplitude in right precordial leads (see Figures 15-58 and 15-59). The electrocardiogram therefore reflects the combined absence of the superior, mid, and inferior portions of the atrial septum.

Figure 15-58 Electrocardiogram from a 5-year-old boy with common atrium, a cleft anterior mitral leaflet, and a 3.5 to 1 left-to-right shunt. The leftward shift of the P wave axis with inverted P waves in leads 2, 3, and aVF indicates an ectopic pacemaker because of an absent sinus node associated with a superior vena caval sinus venosus atrial septal defect. Left axis deviation with counterclockwise depolarization and splintered S waves in inferior leads indicates that the atrial septum was deficient in the ostium primum location. The terminal force of the QRS points to the right, superior, and anterior as in an ostium secundum atrial septal defect.

Figure 15-59 Electrocardiogram from a 57-year-old cyanotic woman with common atrium, pulmonary hypertension, and moderate incompetence of the left-sided component of a common atrioventricular valve. The PR interval is prolonged. A normal P wave axis implies that the sinus node was functioning despite a superior vena caval sinus venosus artial septal defect. Peaked P waves in leads V_4-5 together with QS waves in leads V_1-3 indicate right atrial enlargement, and broad bifid P waves in leads 3, aVL, aVF, and V₆ indicate a left atrial abnormality. Left axis deviation with counterclockwise depolarization and splintered S waves in leads 2, 3, and aVF imply an atrioventricular septal defect with a cleft anterior mitral leaflet. Right ventricular hypertrophy is manifested by tall R waves in right precordial leads and deep S waves in left precordial leads. QRS prolongation is the result of increased duration of the terminal force that is directed to the right, superior, and anterior.

X-Ray

The chest x-ray is similar to that of a nonrestrictive ostium secundum atrial septal defect (Figures 15-54A and 15-60).¹⁸⁷ Enlargement of the left atrial portion of the common atrium is seldom seen in the x-ray, even in the presence of significant mitral regurgitation.

Figure 15-60 X-ray from a 5-year-old acyanotic boy with a common atrium. The electrocardiogram is shown in Figure 15-58. The x-ray resembles an ostium secundum atrial septal defect. Pulmonary arterial vascularity is increased, the pulmonary trunk (PT) and its right branch are dilated, the right atrium (RA) is convex, and a prominent right ventricle (RV) occupies the apex.

Echocardiogram

Echocardiography with color flow imaging and Doppler interrogation identifies a common atrial chamber (Figure 15-61), absence of the atrial septum, and a common atrioventricular valve or a cleft anterior mitral leaflet (see Figure 15-53). The right and left components of the common atrioventricular valve lie at the same level because the atrioventricular septum is absent (see Figure 15-53A). Color flow imaging establishes regurgitation across the left component of the common atrioventricular valve (see Figure 15-53B). The right ventricle is dilated (see Figure 15-53A), the ventricular septum moves paradoxically, and the pulmonary trunk is dilated and pulsatile.

Figure 15-61 Echocardiogram (subcostal) from a female neonate with Ellis-van Creveld syndrome and common atrium (Com Atr). The inferior vena cava (IVC) entered the right-sided portion of the common atrium, and the pulmonary veins (PV) entered the left-sided portion. (LV = left ventricle; RV = right ventricle.)

Summary

The clinical features of common atrium resemble a nonrestrictive ostium secundum atrial septal defect with the following qualifications: (1) symptoms begin earlier and are more pronounced; (2) cyanosis occurs with increased pulmonary arterial blood flow and with insufficient pulmonary hypertension to account for its presence; (3) the P wave axis indicates that the sinus node is absent, and the atrial pacemaker is ectopic because of the deficiency in the superior vena caval sinus venosus location; (4) the QRS exhibits the left axis deviation and counterclockwise depolarization of an atrioventricular septal defect; and (5) echocardiography identifies absence of the atrial septum, a common atrioventricular valve, or a cleft anterior mitral leaflet.

History

Gender ratio with supradiaphragmatic total anomalous pulmonary venous connections is about equal,²⁰⁰ and infrahepatic connection to the portal vein strongly favors males.²⁰⁰ These malformations have been reported in first cousins, siblings, and monozygotic and dizygotic twins and in a father and his two children.^200,205,206 Total anomalous pulmonary venous connection with Holt-Oram syndrome has been described in a family with a history of atrial septal defect.¹⁴³

The clinical course is abbreviated even in the absence of pulmonary venous obstruction. Seventy-five percent to 90% of symptomatic infants do not reach their first birthday, and most are dead within 3 to 6 months.^199,200,207 Only 50% of patients who survive to age 3 months are alive at 1 year.²⁰⁷ The malformation may not be suspected when pulmonary blood flow is increased in the presence of mild cyanosis. Before long, the infant becomes dyspneic and overtly cyanotic, with difficulty feeding and poor growth and development. Those who survive their first year almost always have supradiaphragmatic connections, low pulmonary vascular resistance, and a nonrestrictive atrial septal defect. A 10-year-old boy had an unobstructed infradiaphragmatic connection to the inferior vena cava,²⁰⁸ and a 17-year-old had obstructed infradiaphragmatic connection to the hepatic vein. Exceptionally, patients reach their third, fourth, or fifth decade with relatively little disability and a clinical picture that resembles isolated ostium secundum atrial septal defect except for the mild cyanosis.^209,210 A cyanotic woman with suprasystemic pulmonary vascular resistance was 54 years (see Figure 15-66), and a 62-year-old woman came to necropsy.²¹¹ The oldest reported patient underwent surgical repair at age 66 years.²⁰⁹

In total anomalous pulmonary venous connection with obstruction, lifespan is brief and the clinical course stormy. Tachypnea follows expansion of the lungs because neonatal pulmonary blood flow is obstructed (Figure 15-71).^199,200 Cyanosis is conspicuous because only a small fraction of oxygenated pulmonary venous blood reaches the right atrium for mixing. When an infradiaphragmatic venous channel traverses the esophageal hiatus, feeding, crying, and straining induce additional compression that aggravates the dyspnea and increases the cyanosis. Death from pulmonary edema and right ventricular failure comes within days, weeks, or months after birth. Newborns with infradiaphragmatic connections and asplenia have major esophageal varices.²¹²

Figure 15-71 X-rays from two infants with total anomalous pulmonary venous connection and infradiaphragmatic obstruction. In both x-rays, the lungs show a striking stippled, reticular, ground glass appearance. A, Female infant with infradiagphragmatic obstruction. The transverse liver and symmetric bronchi represent right isomerism. B, Male neonate with total anomalous pulmonary venous connection and atresia of a left vertical vein distal to the venous confluence. The dramatic appearance of the lungs is in marked contrast to the unimpressive cardiac silhouette.

Physical Appearance

In total anomalous pulmonary venous connection without obstruction, mild to moderate cyanosis occurs with increased pulmonary blood flow. Infants with congestive heart failure are catabolic.²⁰⁰ However, a relatively asymptomatic 46-year-old man had been cyanotic since childhood, and a 39-year-old man was never overtly cyanotic. The Holt-Oram syndrome, Klippel-Feil syndrome,²⁰⁰ and cat-eye syndrome sporadically coexist.^213–215

Arterial Pulse and Jugular Venous Pulse

The arterial pulse is small because left ventricular stroke volume is reduced. When the interatrial communication is nonrestrictive, the jugular venous pulse resembles isolated ostium secundum atrial septal defect. At the inception of right ventricular failure, the right-to-left shunt increases and the jugular venous pressure remains relatively unchanged. Pulmonary hypertension with a restrictive interatrial communication results in a large even giant A wave.

Precordial Movement and Palpation

When the interatrial communication is nonrestrictive, precordial movement and palpation resemble nonrestrictive ostium secundum atrial septal defect, although these precordial signs begin earlier. A rise in pulmonary vascular resistance imposes afterload on the volume-loaded right ventricle, so its impulse becomes more striking (Figure 15-72).²⁰⁰ A hyperdynamic right ventricle is not a feature in neonates and infants with pulmonary vein obstruction because pulmonary blood flow is reduced.

Figure 15-72 Tracings from a 13-year-old cyanotic girl with total anomalous pulmonary venous connection, systemic pulmonary arterial pressure, and a confluence of veins that joined the right superior vena cava. The right ventricular (RV) impulse is apparent. The second heart sound (S₂) splits normally during inspiration (Insp.). The prominent pulmonary component (P₂) and the pulmonary ejection sound (E) were transmitted to the fourth left intercostal space (4 LICS). The pulmonary systolic murmur (SM) is attenuated. (A₂ = aortic component of the second sound.)

Auscultation

When the interatrial communication is nonrestrictive, auscultatory signs resemble an ostium secundum atrial septal defect. The tricuspid component of the first heart sound is loud, there is wide fixed splitting of the second heart sound (Figures 15-73 and 15-74), a pulmonary midsystolic murmur is generated by rapid ejection of a large right ventricular stroke volume into a dilated pulmonary trunk (see Figures 15-73 and 15-74), and a tricuspid diastolic flow murmur is common (see Figure 15-73).^200,216 The systolic murmur may have a wide thoracic distribution analogous to the peripheral pulmonary arterial murmurs with ostium secundum atrial septal defect and a hyperkinetic pulmonary circulation.¹¹¹ Pulmonary hypertension is accompanied by a pulmonary ejection sound, attenuation of the pulmonary systolic flow murmur, loss of the tricuspid diastolic murmur, inspiratory splitting of the second heart sound (see Figure 15-72),²⁰⁰ and a high-frequency early diastolic Graham Steell murmur (Figure 15-75). An increased force of right atrial contraction generates a right ventricular fourth heart sound, and right ventricular failure is accompanied by a third heart sound and the holosystolic murmur of tricuspid regurgitation.²⁰⁰

Figure 15-73 Phonocardiogram from a 9-month-old male with total anomalous pulmonary venous connection in which the four pulmonary veins joined the right atrium directly. A restrictive foramen ovale constituted a zone of pulmonary venous obstruction. The first heart sound (S₁) is preceded by a tricuspid diastolic flow murmur (DM) and followed by a pulmonary ejection sound (E) that introduced a prominent midsystolic flow murmur (SM). There is wide fixed splitting of the second heart sound. (A₂ = aortic component; P₂ = pulmonary component.)

Figure 15-74 Tracings from a 9-year-old boy with total anomalous pulmonary venous connection and low pulmonary vascular resistance. A prominent pulmonary systolic flow murmur (SM) ends before both components of a widely split second heart sound. (A₂, P₂ = aortic and pulmonary components; CAR = carotid pulse.)

Figure 15-75 Tracing from a moderately cyanotic 26-year-old man with total anomalous pulmonary venous connection to the right superior vena cava. Pulmonary artery systolic pressure was 87 mm Hg, and the brachial arterial systolic pressure was 106 mm Hg. Phonocardiogram at the lower left sternal edge (LSE) shows a pulmonary ejection sound (E) and a Graham Steell murmur (DM) issuing from a loud single second heart sound (S₂). The ejection sound and diastolic murmur radiated to the apex because the apex was occupied by the right ventricle. (CAR = carotid pulse.)

A continuous murmur is a noteworthy although uncommon auscultatory sign that originates in continuous flow through the venous confluence, the left vertical vein, and left innominate vein (see Figure 15-62).²¹⁷ The continuous murmur has the quality of a soft venous hum and is maximal at the left upper sternal border. Less commonly, a continuous murmur is heard along the right upper sternal border where it is believed to originate from flow through a right-sided anomalous pulmonary venous channel into a right superior vena cava (see Figure 15-68).

In infants with pulmonary venous obstruction, auscultatory signs are determined by pulmonary hypertension rather than increased pulmonary blood flow. More than half of these patients have no pulmonary systolic murmur at all because flow across the pulmonary valve is reduced, but an attenuated midsystolic murmur is generated by ejection into the dilated hypertensive pulmonary trunk. The second sound is single or closely split, and the pulmonary component is loud. A high frequency holosystolic murmur of tricuspid regurgitation accompanies pulmonary hypertensive right ventricular failure.