Atrial septal defect

Fundamentals of clinical cardiology

Atrial

sepal

defect

V. &h&e, M.Sc., Ph.D., M.D., L. Vogelpoel, M.D., M.R.C.P. Cape Town, South Africa

A

trial septal defect is one of the most common forms of congenital heart disease found in youths and adults’ and was encountered in 245 of 1,439 patients with congenital heart disease seen by one of us (VS.) in this Clinic.2 The physical signs are so characteristic that a precise diagnosis can usually be made at the bedside. Electrocardiographic, phonocardiographic, and radiologic examination provides accurate confirmation, so that cardiac catheterization is often not essential. With the development of hypothermic and cardiac bypass procedures these defects are now amenable to surgical correction. However, it is well to have some idea of the natural history of the disease, the anatomic variants and complications, the abnormal hemodynamics produced by these defects, and the influence of the latter on the clinical findings. Embryology Many of the embryologic details responsible for this malformation have been well established, whereas others are still speculative and require further study. Briefly, the endocardial cushions evolve from the middle of the tube-like primitive heart, dividing it into two chambers, one of which is destined to be atria1 and the other ventricular. The cushions themselves contribute to the formation of the atrioventricular valves and the septa.3 The From

F.R.C.P.E.,

septum primum grows downward from the dorsal and cephalic walls of the atrium, and the space between it and the endocardial cushions is known as the ostium primum. This opening is sealed as the septum primum continues to grow and fuses with the endocardial cushions. Communication between the two atria is maintained through the odium secundum, which is formed when part of the wall of the septum primum disappears. Downward growth of the septum secundum covers the foramen primum but leaves an oblique opening-the foramen secundum-through which the flow of blood from the right to the left atrium is maintained. The right atrium is formed by incorporation of part of the right sinus venosus, the inferior vena cava vena cava, and the superior into the primitive right atrium; and, similarly, the left atrium is formed by incorporation of part of the pulmonary veins into the left atrium. Normally, the septum primum and septum secundum fuse after birth, completely separating the two atria. In 12 to 2.5 per cent of healthy subjects the two septa are not united, but are functionally closed, since left atria1 pressure exceeds right atria1 pressure, forcing the two septa together. Reversal of the normal pressure gradient separates the septa and results in a rightto-left shunt through the opening. Deficiency of the septum primum or the

the Cardiac Clinic, Groote Schuur Hospital, C.S.I.R. Department of Medicine, University of Cape Town, Cape Received for publication Oct. 25, 1963.

263

F.R.C.P.

Cardiovascular-Pulmonary Town, South Africa.

Research

Group,

and

the

264

S&ire

and

170gelpoel

septum secundum in the region of the foramen ovale, or abnormal fenestrations, result in ostium secundum defects, which are the most common of all atrial septal defects. Occasionally (3 to 6 per cent of cases), defects occur high in the septum near the entrance of the superior vena cava-sinus venous defects, which are commonly associated with anomalous pulmonary venous drainage. Defects in the development of the endocardial cushions result in endocardial cushion defects or atrioventricularis communis. The dorsal and ventral endocardial cushions divide the common atrioventricular canal into a right (or tricuspid) orifice :Uld a left (or mitral) orifice, thereby separating atria from ventricles. Growth to the left helps form the anteromedial leaflet of the mitral valve, and growth to the right helps form the septal leaflet of the tricuspid valve. Growth upward fuses with the atria1 septum, and growth downward fuses with the ventricular septum. Thus, the endocardial cushions separate the atria1 septum from the ventricular septum, take part in the formation of the atrioventricular valve leaflets, and cnntribute to the formation of the cardiac septa. For practical purposes, malformation of the endocardial cushions results in two main disturbances.4 With the first disturbance (endocardial cushion dejects mithout ventricular septal defect), sufficient veiitricular septal tissue develops to prevent communication between the two ventricles. Deficiency of the atria1 septum always persists, varying from complete absence of the atria1 wall (single atrium) to degrees of partial absence of the septum (ostium primum defect, partia! endocardial cushion defect, partial A-V commuiiis). Varying degrees of malformation of the anteromedial leaflet of the mitral valve are associated, and the tricuspid valve is occasionally affected. It is important to appreciate that, clefts in the mitral and tricuspid valves do not necessarily interfere with the competence of these valves. On the other hand, gross mitral incompetence may be associated with trivial atria1 septal defects.5 In the second disturbance (endocardial cushion defects zwith ventricular septaf defect),

the atria are incompletely separated from the ventricles, the mitral and tricuspid valves are incompletely formed, and the atria1 and ventricular septa are both defective. The size of the ventricular septal defect varies from complete absence of the ventricular septum to deficienq. only. of the upper portion which results in a lack of fixation of the atrioventricular valves. The hemodynamic disturbances of the ventricular septxl defect are addecl to those of the atria1 septal defect and the atrioventricular valves. Rarely have ventricular septal defects with cleft atrioventricular valves but without atria1 septal defects been encountered.” Hemodynamic changes produced by atria1 septal defects. The flow of blood through an atria1 septal defect is, to some extent, determined bv the size of the defect. Jn the rare case jn which the hole is small, ;L relntivel!small amount of blood will flow through it; whereas if the defect is large, as is usually the case, e.g., 2 square centimeters or more, the magnitude of the shunt and its direction will be determined mainl>r by the relative filling resistances of the right and left ventricles. ITsually, the right ventricle offers much less resistance than the left, and the shunt is thus from left to right atrium, resulting in increased right ventricular output.’ Systemic- output is usually normal, whereas pulmonar\ How ma>- exceed systemic as nluch as sixfold. Despite the increased pulmonary flow, the pulmonary arterial pressure is usuall>~ normal or only slightly elevated because or subnormal pulmonary or ;1 Ilormal vascular resistance. Occasionally, changes occur in the small muscular arteries and arterioles in the lungs (particularly in pregnancy), leading to an increased resistance to flow and pulmonar)hypertension.s-” Pressure overwork results in right ventricular hypertrophy which inand creases diastolic filling resistance lowers ventricular acceptance, reducing the left-to-right shunt. When the filling resistance of the right ventricle exceeds that of the left, the shunt becomes predominailtly right to left, leading to arterial desaturation. Right heart failure, however, ma>. result from prolonged volun~c overwork withorit

Atria1

the development of pulmonary hypertension,‘” usually with atria1 fibrillation. But before this is accepted, left ventricular due to hypertension, failure, e.g., that mitral valve disease, thyrotoxicosis, etc., must be excluded.13 Since both atria are in free communication, failure of the left side can be detected early by the elevation of the systemic venous pressure. When malformation of the mitral valve, acquired or congenital, is present, the effects of mitral stenosis or incompetence are superimposed on the changes produced by the atria1 septal defect. Because the left and right atria are in free communication, the pressure effects are dissipated through both atria, which perhaps accounts for the slightly elevated right atria1 pressure and the absence of back pressure on the pulmonary capillaries. Should the tricuspid valve be involved, the effects of tricuspid incompetence are superimposed on the other hemodynamic disturbances present. C\‘hen a ventricular septal defect coexists, the hemodynamic changes do not differ from those produced by an ordinar) uncomplicated ventricular septal defect, except that blood may be shunted directly from the left ventricle into the right or left atrium, or from the left ventricle into the right ventricle and the right atrium because of associated valve deformities. The effects of the ventricular septal defect depend on its size and the pulmonary vascular resistance. Clinical

findings

Characteristic of secundum and sinus venosus defects is the higher incidence in females (3 :2), the rare discovery in infancv, the mild or absent symptoms in the krst three decades of life, and the increasing disability in the third and fourth decades of life due to the late development of heart failure and severe pulmonary hyperter~sion.12~‘4-‘8 Most patients are referred because of murmurs noted during routine physical examination for some unrelated illness or during routine medical examination at school, during pregnancy, or for life assurance. Often, the abnormality is first noted during mass radiography or after radiologic examination for pulmonary infection. Even when attention

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has been drawn to the heart, especially in subjects under 30 years of age, the patient often will not admit to symptoms. When symptoms are present, they usually do not amount to much more than mild effort dyspnea, fatigue, or palpitations, although a background of respiratory infections, especially during childhood, is not uncommon. Often, supposedly symptom-free patients appreciate their preoperative limitations only after the defect has been closed surgically. Most patients are aware of their disease by the third decade of life, although, occasionally, the condition is discovered for the first time in the sixth or seventh decade or later.1g-2” Because of the relatively benign, well-tolerated nature of the condition it is compatible with a full, normal, asymptomatic lifespan. Failure to appreciate this leads to frequent errors in diagnosis in persons beyond middle age and in the elderly.“? A familial occurrence is also well documented but is U~COITII~OI~.~~ These defects are approximately four times L~S common as endocardial cushion defects. Characteristic of endocardial cushion defects, on the other hand, is the equal sex incidence, the common discovery in infants, the severity of the s>-mptoms, the frequent finding of severe pulmonary hypertension, and the increasing disability, so that the condition is recognized at a far earlier age and survival to adulthood is less frequent. 1x~14-27 Exertional dyspnea, fatigue, troublesome palpitations, and recurrent respiratory infections are more prominent, and congestive cardiac failure is not rare. Because the murmurs are much more prominent, attention is drawn to the heart at an earlier age than in patients with secundum defects. Physical

examination

Body development and stature are normal in most patients with secundum or sinus venosus defects, although arachnodactyly, a high arched palate, and a gracile habitus have been noted.Ls Other congenital stigmata are generally absent. Poor bodily growth and retardation of development tend to be more common in patients with endocardial cushion defect, especially when the complete variety is present. Septal defects are common in

266

Schrire

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Mongolism: the complete variety of endocardial cushion defect is the most frequent association.“gr30 The jugular venous pressure and pulsations are normal, except in the presence of cardiac failure. The peripheral pulse and blood pressure are normal. Atria1 septal defect is the one congenital heart condition in which atria1 fibrillation occurs with any degree of frequency. This is probably related to the age of the patient, since it rarely occurs before the fourth clecade. When present, especially at an early age, associated mitral valve disease (Lutembarher’s syndrome)31 should always be suspected. Palpation of the chest is very important. Clear evidence of diastolic overload of the right ventricle is usually present. The forceful, often heaving type of apex can be mistaken for an overactive left ventricle. The apex, however, is formed by the enlarged right ventricle, which can readily be recognized by the parasternal lift which is continuous with the apical thrust. Pulsation over the outflow tract and pulmonary artery is frequently visible and palpable, and an accompanying thrill is not rare, especially when the chest wall is thin and a left parasternal bulge is present, deforming the thoracic cage. When atria1 septal defect is complicated by gross mitral incompetence or a ventricular septal defect, the apex is left ventricular in type, and a low parasternal thrill may be present. Auscultation A pulmonary ejection systolic murmur is nearly alwavs present, usually Grade 2-3/6 in intensity, differing in no way from the innocent pulmonary systolic murmur of youth and childhood. Occasionally, it is very loud (Grade S/6) and associated with a thrill, which usually but not necessarily is due to a gradient across the pulmonary valve. It is well heard in the back below the scapulae, presumably because of downward conduction through the pulmonary arteries. One of the most important diagnostic findings is a diastolic murmur in the tricuspid area, often with high pitch and varying a distinctive remarkably with respiration; in fact, it sometimes becomes audible only at the

Am. Ifcart

J.

August,1964

height of inspiration. At times, this murmur is loud and widespread, radiating to the apex. Since the apex and the whole front of the heart is formed by the right ventricle, the murmur mav be mistakenly attributed to mitral stenosis. The murmur is caused by the increased flow across normal tricuspid valves. When the murmur is soft and high pitched, differentiation of it from the murmur of pulmonary incompetence may be difficult, because both murmurs commence at nearly the same phase of diastole; the pulmonary diastolic murmur is delayed because of prolongation of right ventricular systole, and the tricuspid valve opens early because of increased atria1 filling. Pulmonary incompetence can only be diagnosed with certaint). when the murmur is localized to the pulmonary area or when severe pulmonary hypertension is present. .q pansystolic murmur at the apex indicates the presence of mitral incompetence and is often accompanied by an apical mid-diastolic murmur. Ii1 endocardial cushion defect the murmur tends to radiate medially rather than laterally.1”,3” In fact, it may be mistaken for the murmur of a ventricular septal defect radiating toward the apex. The peculiar situation of the valve deformity results in an anteromedially directed jet. Thus, a loud systolic murmur at the tricuspid area, oftelz with u thrill, may be due to mitral incompetence, tricuspid incompetence, or a ventricular septal defect. Abnormal splitting of the second sound is one of the most striking physical signs in atria1 septal defect.17 The width of splitting is not the feature, since splitting is most commonly not more than 0.04 second in held expiration, but fixity of the split, to the ear, is characteristic. Normally, the second sound closes completely on expiration and widens to a variable extent on inspiration, and it is the change from a split to a single sound that can be readily appreciated. Although phonocardiographically some change in the degree of splitting is often present, it is extremely difficult at the bedside to appreciate movement of the second sound, when the sound is never single or narro\vly split. It is likewise very difficult to appreciate movement of the widely split

Atria1 septal defect

second sound of pulmonary stenosis or ventricular septal defect. The pulmonary component of the second sound is usually of normal intensity, except in the presence of pulmonary hypertension. When severe pulmonary hypertension is present, e.g., in Eisenmenger’s syndrome, wide splitting of the second sound is said to indicate atria1 septal defect. 33 We have been deceived by this sign in 2 patients with reversed patent ductus, and in cases of proved atria1 septal defect we have found single second sounds. An early systolic ejection sound or click34 usually indicates pulmonary hypertension or marked pulmonary arterial dilatation. Wide splitting of the first sound with accentuation of the tricuspid component, presumably due to overdistention of the right ventricle with delayed closure of the tricuspid valve, is commonly encountered. Confusion with the pulmonary ejection sound can readily occur. The loud first sound may raise a suspicion of mitral stenosis. In our experience with approximately 300 patients who had an atria1 septal defect, we found four fairly clearly defined clinical patterns: (1) Classic atrial sepsal defect. The majority of secundum and sinus venosus defects and approximately 25 per cent of endocardial cushion defects fall into this group. The signs are those of increased flow across the pulmonary and tricuspid valves without evidence of atrioventricular valve disease or ventricular septal defect. (2) Atria1 sepal defect with mitral incompetence. Approximately half our patients with endocardial cushion defects presented signs of mitral incompetence in addition to those of increased flow across the pulmonary and tricuspid valves. Rarely does rheumatic or even congenital mitral incompetence complicate secundum defects. (3) “Ventricular septal defect” with or without mitral incompetence. This occurred in approximately 25 per cent of our cases of endocardial cushion defects and in cases of secundum defects associated with independent ventricular septal defects. The clinical signs are dominated by a systolic murmur, often with a thrill at the fourth left intercostal space, whether a ventricular septal defect is in fact present or not. Pulmonary systolic murmurs,

267

splitting of the second sound, and mitral murmurs occur so frequently in uncomplicated ventricular septal defects that an atria1 septal defect may not even be SIISpetted. (4) Eisenmenger’s syndrome. Phonocardiography Typical phonocardiograms of secundum and primum atria1 septal defects are shown in Fig. 1. Pulmonary, atrioventricular, and ventricular septal defect murmurs have well-known configurations by which they can usually be recognized. The relatively fix& splitting of the second sound has been amply documented35 and analyzed.36*37 Normally, on inspiration the pulmonary component of the second sound (P2) moves away from the aortic, component (AZ) because of the increased right ventricular filling and prolongation of right ventricular systole associated with the increased SJXtemic venous return to the heart. On expiration, P, moves in (right ventricular systole is shortened) and AZ moves out because of prolongation of left ventricular systole associated with the increased pulmonary venous return. Splitting on inspiration is followed by superimposition of AZ and Ps on expiration. In atria1 septal defect the two atria can be considered to be a common mixing chamber, and flow into either ventricle is determined by the relative compiiance of these two chambers. The increased filling of the right atrium on inspiration is balanced by the diminished shunt from left to right atrium, prolongation of right ventricular systole resulting in splitting of the second sound. On expiration the increased filling of the right atrium from the left maintains right ventricular prolongation and persistence of the splitting. Electrocardiography The P waves are usually of normal contour; occasionally, left or right or biatrial hypertrophy is present.38 The P-R interval is usually normal but is more commonly prolonged in endocardial cushion defects than in secundum defects. Right axis deviation, with a mean QRS vector in the frontal plane between +90 and +15O degrees and a clockwise loop, is characteristic of secundum and sinus venosus defects, and is present in the majority of patients.18s34*42 On the other hand, in the

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majorit) of patients with endocardial cushion defects the mean QRS vector lies between -30 and - 120 degrees (Fig. 2) with a counterclockwise 10op.‘~~““-“~ These two distinctive patterns (Fig. 3) nearly always clearly separate the two conditions. It is more common, however, to find patients with secundum defects who have left axis deviation than to find patients with endocardial cushion defect who have a normal axis”,6 (Fig. 3) or right axis devi-

ation. In fact, the latter is highly exceptional.47 ,4 t\,pical rsR’ or rsR’S’ pattern in Lead ir1 (incomplete RBBB” or diastolic overload of the right ventricle”“) is frequently present in both conditions. A tall R in Lead V1 or an rR pattern suggestive of right ventricular hypertrophy, or a qR or qRs pattern is not uncommon, and, contrary to what has been reported b\. Davies and associates,= is not, in our

with an uncomplicated secundum defect Fig. 1. Phonocardiographic recording. 9 from a patient (A, lest) and from a patient with an endocardiai cushion defect (I?, right) without a ventricular and the jugular vein (JL%) septal defect. Synchronous tracings from the carotid artery (CAR) are shown in A; and in both A and B the tracings are taken from the pulmonary area (PA ), the tricuspid area (4LS), and the mitral area (MA). The PA and JLS tracings are recorded synchronously. At the pulmonary area in both A and R the pulmonary systolic murmur is ejec.tion in type and is produced by increased flow across normal pulmonary valves. Wide splitting of the second sound (Z,Z) is present. At the tricuspid area in A the systolic murmur is ejection in type, radiating down from the pulmonary valves, and a tricuspid flow murmur (DM) associated with increased volume If blood flowing across normal tricuspid valves is recorded. The latter is well shown at the mitral area, where it may be mistaken for the murmur of mitral stenosis. At the tricuspid area in B the systolic murmur is pansystolir and of high frequency, so that it can readily be mistaken for the murmur of a ventricular septal defect. In fact, it is produced by the medial radiation of the mitral systolic murmur. The mid-diastolic murmur is probably due to fusion of a tricuspid flow murmur and an organic mitral diastolic murmur.

Atriul

related to the pulmonary arexperience, terial pressure. Complete right bundle branch block, although frequently associated with pulmonary hypertension, occurs not uncommonly with relatively normal pulmonary arterial pressures and normal resistance. The additional finding of inverted T waves in Leads VI-V4 in adults was, in our experience, the only reliable electrocardiographic evidence of pulmonary hypertension. Small q waves in Leads V6-V7 occurred in more than a third of our patients and does not necessarily suggest an additional cause for left ventricular strain as suggested by ToscanoBarboza and associates. 39 Right axis deviation with a clockwise loop and a right ventricular “diastolic overload” or right ventricular hypertrophy pattern is not pathognomonic of secundum defects, since it occurs not infrequently in other forms of congenital heart disease, such as pulmonary stenosis, as well as in acquired heart disease, such as mitral valve disease and car pulmonale. A similar tracing is occasionally encountered as an isolated congenital abnormality, sometimes associated with a pulmonary systolic murmur, a dilated pulmonary artery, and wide splitting of the second heart sound.4g Jn such a case, cardiac catheterization is required in order to establish the diagnosis. However, when the clinical picture is that of an atria1 septal defect, an electrocardiographic tracing of this kind is invaluable in differentiating secundum defect from endocardial cushion defect. On the other hand, left axis deviation with a counterclockwise loop and a diastolic overload or right ventricular hypertrophy pattern in an acyanotic patient is highly suggestive of defects in the region of the atrioventricular valves.6 It is, however, encountered in uncomplicated ventricular septal defect (15 per cent of Toscano-Barboza and DuShane’s 60 patients50). Radiologic

sepal

deject

260

thoracic ratio above 50 per cent; this is due entirely to enlargement of the chambers of the right side of the heart and the main pulmonary artery. Generally, the larger the shunt, the greater the cardiothoracic ratio. Patients with endocardial cushion defects usually have even larger hearts, with an average cardiothoracic ratio of 60 per cent. l* Left ventricular enlargemeiit is difficult to assess in the presence of right ventricular enlargement because of displacement by the enlarged right ventricle. Left atria1 enlargement is rare, and, when noted, indicates involvement of the mitral valve. The small aorta and large main and left pulmonary arteries (Fig. 4) produce a characteristic silhouette in the anteroposterior projection. The lung fields show the classic features of pulmonary plethora, with widely dilated pulmonary arteries proceeding well out to the periphery of the lung fields; the rounded shadows of these vessels can be seen end on. So characteristic is the appearance that, in a given patient with secundum atria1 septal defect, the degree of left-to-right shunt can be fairly accurately assessed from a good

findings

The radiologic findings are frequently so characteristic that the diagnosis can often be made on screening or from the x-ray plates; in fact, the condition is not infrequently discovered for the first time during this type of investigation. The heart is usually enlarged, with a cardio-

Fig. 2. The mean QRS vector in the frontal pIane in 85 patients with surgically proved secundum defects, and in 31 patients with surgically or necropsy proved endocardial cushion defects. In secundum defects the mean asis usuallv lies between +90 and + 150 degrees; in endorardjal cushion defects it lies between -30 and -120 degrees. Secundum defects with left axis occur more commonly than . deviation endorardlal cushion detects with normal axes.

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Schrire and Vogelpoel

posteroanterior film. Small shunts are characterized by the presence of plethora in the upper or mid zone, whereas large shunts are characterized by the presence of plethora throughout the lung fields.5l Peripheral pruning, i.e., a sharp tapering off in caliber of the main pulmonary arteries, is seen in patients with a pulmonary systolic pressure above 60 mm. Hg. The striking feature of patients with severe pu!monary hypertension is the marked contrast between the enormously dilated main vessels near the hilum and the attenuated thread-like vessels and clear lung fields in the periphery. Hilar dance, or marked pulsation of the pulmonary arteries on fluoroscopy, is the hallmark of atria1 septal defect; the excursions are greater in these patients than in those with any other left-to-right shunt. Radiology is of considerable value in determining the presence of a left-to-right shunt but does not differentiate a secnndum front an endocardial cushion defect. Anonialous pulmonary veins which enter the superior vena cava or the right atrium are difficult to see on plain films but can sometimes be clc~ly outlined by tomoy-

Fig.

3. Typical

electrocardiograms

found

raphy.52 Kerley B lines,53 fine horizontal lines observed at the periphery in the basal regions and ascribed to pulmonary venous hypertension, are seen occasionally, and usually indicate associated mitral stenosis. Cardiac

catheterization

Cardiac catheterization is most helpful in establishing the presence of an atria1 septal defect, the size of the left-to-right shunt, the pulmonary vascular resistance, and the presence or absence of associated defects. Yet it often fails to differentiate a secundum from a primum defect. The following points, however, are worth rcmembering. A left-to-right shunt at the atria1 level can always be detected in both conditions, but can, of course, also occur in the case of a ventricular septal defect with tricuspid incompetence and a left ventricular right atria1 c.omlnullic;ltiotl. When the catheter is withdrawn directly from the left to the right ventricle (Fig. sj without traversing an atrium, an endocardial cushion defect is ljresent. :I low c-rossingfrom right to left ;~trium, a further step up in oxygen satui-atioll from right ;ttrium t-o right, ventricle, ;lutl almost

in cases of secundum

defect

(A)

and of endocardial

cushion

defect

(B).

Atria1 sepal deject

identical dye-dilution curves from left and right pulmonary arteries favor endocardial cushion defects but are also found ill cases of secundum defects. Hemodvnamic evidence of mitral incompetence *is uncommon because the two atria form a large common chamber which dissipates the pulse waves, and, in any case, secunclum have

defects

with

mitral

271

with a right ventricular pressure of 80 mm. Hg in a patient who had no narrowing of the pulmonary valve at the time of operation, and in whom recatheterization

incompetence

the same effects as incompetent split mitral valves. Differentiation of an endocardial cushion defect without a ventricular septal defect from one with a ventricular septal defect is even more difficult. I,eft ventricular angiocardiography and intracardiac phonocardiography are the best techniques available for this. Severe pulmonary hypertension and a significantly reduced arterial oxygen saturation usually favor the presence of a large ventricular septal defect. Sinus venosus defects and anomalous pulmonary venous drainage can usually be detected at catheterization. The latter is best determined by the dye-dilution technique, since it is not always easy to be certain whether a catheter passed from the right atrium into a pulmonary vein has reached there directly or through an atria1 septal defect. Common

associations

1. Pulmonary valve gradient. A

loud puImonary systolic murmur accompanied by a thrill in the pulmonary area is not a reliable indication that a gradient exists between the right ventricle and the pulmonary artery.‘” We have found loud murmurs and thrills in patients with uncomplicated atria1 septal defects without gradients, and, conversely, gradients have been found when not clinically suspected. Wide splitting of the second sound, e.g., up to 0.07 second or more, can occur without a gradient. However, when the phonocardiogram shows the pulmonary systolic murmur extending beyond A2, we have always found a gradient. In our experience, the gradient has always been at gradient, valve level ; ar~qr infundibular when present, has always been trivial. Demonstration of a difference in systolic pressure does not necessarily indicate that true valvular stenosis is present.ln We found a gradient as high as 50 mm. Hg

Fig. 4. In A, a large left-to-right shunt with pulmonary arterial enlargement, increased pulmonary arterial markings, right atria1 and right ventricular enlargement is present. In B. severe pulmonary hypertension is present. The slight displacement of the heart to the left (commonly encountered in cases of atria1 septal defect) exposes the markedly enlarged, pruned right pulmonary artery. The oligemic peripheral lung fields contrast sharply with the gross enlargement of the main pulmonary arteries.

a year after repair of the defect showed normal right ventricular pressures and no gradient. I8 It is probable that the murmur and thrill in such patients is produced bl a large flow through a valve ring which does not dilate to the same extent as do the pulmonary artery distally and the right ventricle proximally, thus resulting in an area of relative narrowing. It is our practice, therefore, to diagnose organic pulmonary valve stenosis only when a disproportionately large gradient is found with a small left-to-right shunt. True organic puhnonary stenosis of varying severity undoubtedly exists. An extreme example is severe pulmonary stenosis with intact ventricular septum and reversed atrial shunt. Although the

Fig. 5. LVithdrawal of the catheter directly from the left to the right xrentricle without traversing an ntrium excludes secundum atria1 srptal defect but does not differentiate a complete from ZL partial endocardial cushion defect

shunt is usually through a stretched foramen ovale, a true secundum defect ma\ be present. Severe pulmonary stenosis alters the distensibility of the right ventricle, so that resistance to filling maq be only slightly less than, equal to, or exceed that of the left ventricle. As a result, a slight left-to-right shunt, no shunt, or a right-to-left shunt may be present, as occurs in Fallot’s pentalogy.5.‘*55 Obstruction at the tricuspid valve or hypoplasia of the right ventricle produces similar effects on the shunt. 2. Pulmonary hypertension. When the pulmonary vascular resistance increases, the physical signs alter. As the signs of pulmonary hypertension begin to dominate the picture, the magnitude of the left-toright shunt progressively diminishes. Thus, the pullnonary and tricuspid murmurs are rctluced or abolished, the second sound becomes loud, and splitting either persists, diminishes, or disappears. ;i pulmonnr)systolic ejection sound is nearly always and pulmonary incompetence 1s present, frequent. When a right-to-left. shunt is established, cyanosis and clubbing result. Trlvestigation by cardiac: catheterization at this stage carries with it a significantlq illcreasetl risk. ITsually, the process takes in the case ;I slumber of years to develop of secundum defects, but, occasionall>., particularly after pregnancy, the course is more rapid. The ultimate clinical picture is that of Eisenmenger’s syndrome. Episodes suggestive of acute pulmonar) arteri;ll thrombosis frequently occur in the late stages of pulmonary hypertension, ;jntl massive thrombosis of the main branches can sometimes be recognized 011 the plain chest s-ray fillI]. In the colnplete variety of endocardial cushion defect with a large ventricular septal defect, the signs of severe pulmonar) hypertension occur at a far earlier age, and severe disability in infanrv is the general rule. ‘The rlil;ical picture ‘is uearer that of ;I large ventricular septal defect than that of an atria1 septal defect. 3. &srnmengrr’s syndrome. Severe pulmonary hypertension with a reversed shunt- at either the atrial, ventricular, or pulmonary arterial level characterizes Eisellnlenger’s syndrome.33 The clinical pictures ma). be identical, whatever the

A frial sepfal defect

pathology. Atria1 septal defect can be suspected by the persistence of splitting of the second heart sound, the disproportionate size of the pulmonary arteries, and the presence of right bundle branch block. The diagnosis can be made with certainty only by catheterization and angiocardiography. mitral 3. dlitral valve disease.Rheumatic valve disease complicating secundum defects occurs in approximately 10 per cent of the cases14~L8~56; congenital mitral valve disease is rare. Congenital mitral valve disease almost always accompanies endocarclial cushion defect and is of hemodynamic consequence in 75 per cent of the cases.** Rheumatic involvement in endocardial cushion defect must be extremely rare and would be very difficult to recognize. Rheumatic mitral valve disease commonly takes the form of stenosis; incompetence is less frequent. The clinical diagnosis in the most severe cases is difficult. The left atrium is decompressed by the free communication between the left and right atria, thus minimizing the signs dependent upon a large diastolic gradient across the mitral valve, namely, a loud

2 73

first sound, opening snap, and long diastolic murmur with presystolic accentuation. None of our patients had the classic signs of mitral stenosis. Moreover, obstruction to flow through the mitral valve had the effect of increasing the left-to-right shunt so that the signs of the atria1 septal defect dominated the clinical picture. It is probable that the signs of mitral stenosis become conspicuous only when the atria1 septal defect is small, thereby permitting a rise in left atria1 pressure and a mitral vaIve gradient. Recognition of mitral stenosis at catheterization may also be difficult because left and right atria1 pressure equalize. If the left ventricle can be entered, the gradient across the mitral valve can be determined on a withdrawal tracing. The presence of a high right atria1 pressure and of atria1 fibrillation should always alert one to the possibility of associated mitral stenosis. \4’e have found radiologic evidence of left atria1 enlargement 01111 in patients with Lutembacher’s syndrolne, and regard this as an important sign. The electrocardiogram has been of no help. Mitral incompetence is recognized by the presence of a loud pansystolic murmur

Fig. 6. Electrocardiogram from a patient with Eisenmenger’s syndrome, associated with a large atria1 septal defect at catheterization. Right axis deviation and severe right ventricular hypertrophy are present. The presence of large Q waves in the left ventricular leads indicated an additional ventricular septal defect, which was confirmed at a second catheterization.

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at the apex which is completely different from the pulmonary ejection murmur. It may be accompanied by a diastolic rumble. In the case of endocardial cushion defect the murmur tends to radiate more medially than it does in the case of rheumatic mitral incompetence. However, the two conditions will usually be differentiated b>. the electrocardiogram. Other congenital malformations of the mitral valve are occasionally encountered, particularly in the case of endocardial cushion defects. These includes conditions such as double or even triple mitral orilices.18’25.5i 5. Partial and total anomalous pulmonary venous drainage; single atrium. These three conditions can present a clinical picture identical to that of atria1 septal defect. Partial anomalous pulmonary venous drainage is usually associated with an atria1 septal defect and is recognized at catheterization5* (vide supa). It is fairly constantl) present in a sinus venosus defect. Single or multiple veins may drain anomalously, with the right lung usually being involved. In the rare cases of partial anomalous pulmonary venous drainage with an intact atria1 sept urn, splitting of the second sound has been reported to behave normally during respiration, 36but this has not been a constant experience in our patients. If in addition to the signs of an atria1 septal defect a continuous murmur is heard under the clavicle, usually the right one, and the patient is cyanotic, total anomalous pulmonary venous drainage can be diagnosed at the bedside. Occasionally, clinical cyanosis is absent and reliance can be placed on the radiologic findings (the “figure-ofeight” appearance of anonlalous drainage into the superior vena cava,60 and the “scimitar” sign of drainage into the inferior vena cava6’). Single atrium is often but not constantly associated with left axis deviation in the ECG and also cannot be distinguished except bv special catheterization and angiocardiographic techniques. We have encountered car triatriatum with an atria1 septal defect at operation in a patient in whom the preoperative diagnosis was that of secundum septal defect. 6. Atria1 septal dej’ect plus ventricular septal defects. A secundum defect may be

associated with the usual type of ventricu-

.4rn. Hcuvt .I. .4rrgrcst, 1964

lar septal defecLfi” Clinically, the ventricular septal defect dominates the filldings, whereas the atria1 septal defect is recognized at cardiac catheterization. Tricuspid incompetence must be excluded. The electrocardiogram usually helps to differentiate this condition from an endocardial cushion defect. When the ventricular septal defect is large, severe pulmonary hypertension and reduced distensibilit\v of the right ventricle are present. The atria1 shunt, therefore, becomes right to left, at a time when the ventricular shunt is still left to right. This leads to the paradox of central c‘yanosis, associated with the persistence ot a short murmur of ventricular septal defect and pulmonary plethora.“” In the presence of a high peripheral arterial resistance (Eisenmenger’s syndrome) the murmurs disappear, and both the atria1 and the ventricular septal defects ma>. be completely missed, unless sought for at catheterization. Persistent large Q waves in the left lateral precordial leads in cases of Eisenmenger atria1 septal defect suggests this diagnosis (Fig. 6). 7. Awial sepal defects in injancy. Atria1 septal defects of the secundum type are generally asymptomatic in infancy. \Il’heil disabilit). is present, an endocardinl cushion defect is usually present. However, heart failure in infants with apparently uncomplicated secundum defects is well docunlented,6” and unless one is aware of this, a potentially curable condition may be missed. 8. Small atria1 septal defects. Most atria1 septal defects are large: in ‘fact, at operation the defect is seen generally to have a diameter of at least 2 cm. When an uncomplicated atria1 septal defect is recognized at the bedside, the shunt is usuallv over 50 per cent and the defect large. Kadiologicall-)shunts between 40 and 50 per cent can sometimes be detected,51 but in the case of smaller defects the x-ray picture is normal. Small atria1 septal defects, however, are ~~nconlmon.~~Actually, this may Ilot be so, since small defects may be missed clinicall> and at necropsy. Generally, we have found small defects in association with mild pulmonary stenosis: the clinical presentation is that of mild pulmonary stenosis. Wide splitting of the second sound with a Ilornlal to loud pulmonary secontl sountl a~ltl 110

Atria1

change in intensity of the pulmonary systolic murmur when amyl nitrite is inhaled may suggest this combination at the bedside.55 Small atria1 septal defects may also occur in cases of endocardial cushion defects, with the clinical picture being that of severe mitral incompetence.5 The defect may be completely missed unless careful catheterization is performed. 9. Bacterial endocarditis. Bacterial endocarditis complicating atria1 septal defect uusafly indicates an endocardial cushion defect and is uncommon.5 The abnormal valves or the ventricular septal defects are affected. Involvement of the atria1 septal defect itself is extremely rare, with the secundutn defect complicated by bacterial endocarditis being highly exceptional65 (5 patients in all), and even in these cases the pulmonary or tricuspid valves have usually been affected. Paradoxical emboli and brain abscess are very rare hazards. 10. Rheumatic heart disease. Discussion of the subject would not be complete without making mention of acquired valvular disease. The physical signs produced by mitral, aortic, and tricuspid valve disease closely resemble those of endocardial cushion defect, and the condition of several of our patients in the medical outpatient department masqueraded for years as rheumatic heart disease. The major clues are the electrocardiogram and the radiologic evidence of pulmonary arterial plethora, in contrast to pulmonary venous distention. A rare presentation is that of mitral incompetence, with split mitral valves and a small atria1 septal defect found at operation.5 Secundum defects are most commonly confused with mitral stenosis because of the wide radiation of the tricuspid diastolic murmur to the apex and the signs of right ventricular overload. A particularly common mistake occurs during pregnancy when the circulatory changes are accentuated. Surgery In a condition which is, generally, as benign as uncomplicated ostium secundum defect a remarkably low mortality and morbidity is obligatory before operation can be recommended. This has been achieved in most good centers: the operative mortality has varied from 0 to 1 per

septal dqfert

255

cent, depending on whether hypothermia or cardiopulmonary bypass was used. In our own tinit, we have had no morta1it.y in our first 92 patients. Generally speaking, operation is advised in patients with a leftto-right shunt of 50 per cent or more (this includes most patients whose condition is recognized clinically), and age is no barrier. When severe pulmonary hypertension is present, the operative risks are greater, but provided that the dominant shunt is still left to right, operation is advisable. When sinus venosus defects or anom;Jous pulmonary venous drainage is present, cnrdisc bypass is the method of choice, and profound hypothermia is often neressar>., with discontinuance of b>.pass while the defects are repaired. The mitral valve should always be felt, particularly when mitral stenosis is suspected, although this increases the risks of air embolism. It must be appreciated that complete abolition of all left-to-right shunting caimot be guaranteed even with the most meticulous technique. L4 small, insignificant shunt can be detected in at least 10 to 2.5 per cent of the patients if careful postoperative catheterization is performed.‘X~“G~67 The only safe technique for surgical correction of endocardial cushion defect is whole-body perfusion, with or without hypothermia. When a ventricular septal defect is absent, a mortality of 7 to 27 per centGR has been reported, which is acceptable when the severity of the condition and the poor life expectancy are considered. Particular care must be taken in correctiilg the mitral incompetence, in dividing abnormal chordal restraints and avoiding heart block, and a patch is always necessary. Some degree of mitral incompetence frequently persists after operation. In cases of endocardial cushion defects with ventricular septal defect the operative mortality is generally above 60 per cent and is dependent on the size of the defect and the pulmonary resistance. When the defect is large and the pulmonary resistance high, the risks are prohibitive. \Ve nish to thank our medical and surgical colleagues in the Cardiac Clinic and the Cardio-Thoracic Ilnit for their collaboration, and the Superintendent, Dr. J. G. Burger, for permission to publish. Our thanks are due to the Council for Scientific and Industrial Research and the City Council of Cape Town for their continued support.

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REFERENCES 1. VVood, 2:639.

I’.:

22. Congenital

heart

disease,

Brit.

M.

J.

8:198,

1950.

2. Schrire, VT.: Experience with congenital heart disease at Groote Schuur Hospital, Cape Town. South African M. 1. 37:1175. 1963. 3. Wakai, C. S., and Edward;, J. E.: SykposiumDevelopmental and pathological considerations in persistent common atrioventricular canal, I’roc. Staff Meet. Mayo Clin. 31:487, 1956. 4. Barnard, C. N.. and Schrirc, V.: The surgical correction of endocardial cushion defect, Surgery ,49:500. 1961. 5. Brockenbrough, E. C., Braunwald, E., Roberts, \V. C., and Morrow, .A. G.: Partial persistent ntrioventricular canal simulating pure mitral regtirgitation, An,!. HEART J. 63:9, 1962. 6. Burchell, H. B., DuShane, J. \V., and Brandenburg, R. 0.: The electrocardiogram of patients \vith atriovcntricular cushion defects. (Defects of the atrioventricular canal I, Am. J. Cardiol. 6:575,

7.

8. 9.

19:403.

25.

26.

27.

28. 29. 30.

31.

32.

1957.

Burchell, H. B.: Studies in pulmonary hypertension in congenital heart disease, Brit. Heart J. 21:255, 1959. 11. Heath, I)., Helmholtz, H. F., Burchell, H. B., DuShane, J. W., Kirklin, J. W., and Edwards, J, E.: Relation between structural changes in the small pulmonary arteries and the immediate rev-ersibility of pulmonary hypertension following closure of ventricular and atria1 septal defects, Circulation 18:1167, 1958. 12. Campbell, M., Neil], C., and Suzman, S.: The prognosis of atria1 septal defect, Brit. M. J.

10.

13. 14.

1:1375,

1957.

Ijester,

L.: Atria1

18:209,

1956.

16. 17. 18.

19. 20. 21.

defect,

Brit.

Heart

34.

35.

36.

J.

Bedford, 1). E., Sellers, T. H., Somerville, W., Belrher, J. R., and Besterman, E. M. M.: Atria1 septal defect and its surgical treatment, Lanret 1:12.55,

15.

33.

37. septal

38.

1961.

39.

40.

41.

42.

1957.

VVakai, C. S., and Edwards, J. E.: Pathologic study of persistent common atrioventricular canal, AM. HEART J. 56:779, 1958. Anderson, I. M., and Coles, H. M. T.: Endocardial cushion defects, Brit. M. J. 1:696, 1961. Scott, L. P., Hauck, A. J., Nadas, A. S., and Gross, R. E.: Endocardial cushion defect. Preoperatke and postoperative survey, Circulation 26:218, 1962. VVood. P. H.: Diseases of the heart and tirculation, London, 1956, Eyre & Spottiswoode, Ltd. Taussig, H. B.: Congenital malformations of the heart, Cambridge, 1960, Commonwealth Fund. Rowe, R. D.. and ITchida. I. A.: Cardiac malformation in Mongolism, Am. J. Med. 31:726. 1961. Lutembacher, R.: De la stenose mitrale avet‘ communication interauriculaire. Arch. mal. coeur 9:237, 1916. Lefevre. T. M., Magidson, O., and Kay, J. H.: Endocardial cushion defect: Diagnosis and surgical treatment, New England J. Med. 266:480, 1962. Wood, P.: The Eisenmenger syndrome, Brit. M. J. 2:700, 1958. Leatham, .4., and Vogelpoel, L.: The early systolic sound in dilatation of the pulmonary artery, Brit. Heart J. 16:21, 1954. Leatham, A., and Gray, I.: Xuscultatory and phonocardiographic signs of atrial septal defect, Brit. Heart J. 18:193, 1956. Shafter, H. E.: Splitting of the second sound, Am. J. Cardiol. 6:1013, 1960. Aygen, M. M., and Braunwald, E.: The splitting of the second heart sound in normal subjects and in patients with congenital heart disease, Circulation 25:328, 1962. Sanchez-Cascos, A., and Deuchar, I).: The I’ wave in atria1 septnl defect, Brit. Heart J. 25:202.

1957.

Roesler, H.: Interatrial septal defect, Arch. Int. Med. 54:339, 1934. Bedford, D. E., Papp, C., and Parkinson, J.: Atria1 seotal defect. Brit. Heart I. 3:37. 1941: Barber, i. M., Makidson, O., and Wood, P., Atria1 septal defect,Brit. Heart J. 12:277, 1950. Schrire. V’.. Beck. W.. Voeelpoel. L.. Nellen. M.. and Barnard, C. ‘N.: ‘At&l septal defect, South African M. J. 37:727, 849, 1963. Coulshed. N., and Littler, T. R.: Atria1 septal defect in the aged, Brit. M. J. 1:76, 1957. Colmers. R. A.: Atria1 septal defects in elderly patients; :1m. J. Cardiol.‘l:768, 19.58. Ellis, F. H., Brandenburg, R. O., and Swan, I-1. J. C.: Defect of the atria1 septum in the elderly, New England J. Med. 262:219, 1960.

I. J.: :\trinl sep.4m. J. Cardiol.

2.1. Zuckerman, H. S., Zuckerman, G. H., Mammen. 1~. E., and Wassermil, M.: atria1 septal defect. Familial occurrence in four generations of one family, AAm. J. Cardiol. 9:515, 1962. 21. Campbell, M., and Missen. G. A. Ii.: Endocardial cushion defects. Common atrioventricular canal and ostium primum, Brit. Heart J.

1960.

Bargcr, J. I)., Edwards, J. E., Parker, R. L., and I)ry. ‘1’. J.: Atria1 septal defect: Presentation of a case with obstructive pulmonary vascular lesions caused by metastatic carcinoma, Proc. Staff Meet. Mayo Clin. 23:182, 1948. Evans, WT.: Congenital pulmonary hypertension, Proc. Roy. Sot. Med. 44:600, 1951. Heath, I)., and Whitaker, W.: The small pulmonary vessels in atria1 septal defect, Brit. Heart J. 19:327,

Sommer, L. S., and Voudoukis, tal defect in older age group,

1963.

l‘osc,;rllo-Barboza, E., Brandenburg, R. O., and Swan, H. J. C.: Atria1 septal defect. The electrocardiogram and its haemodynamic correlation in 100 proved cases, .4111. J. Cardiol. 2:698, 1958. Martins de Oliveira, J., and Zimmerman, H. .\.: The electrocardiogram in interatrial septal defects and its correlation with hemodynamics, AM. HEAR.~ J. 55:369, 1958. Walker, W. J., Mattingly, T. W., Pollock, B. E., Carmichael, D. B., Inmon, ‘I‘. W., and Forrester, Ii. H.: Electrocardiographic and hemodynamic correlation in atria1 septal defect, AM. HEART J. 52:547, 1956. Davies, D. H., Pryor, R., and Blount. S. G.: Electrocardiographic changes in atria1 septal

Atria1

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

5.1.

5-l.

defect following surgical closure, Brit. Heart J. 22:274, 1960. Toscano-Barboza, E., Brandenburg, R. O., and Burchell. H. B. : Electrocardioeraohic studies of cases with intracardiac malformations of the atrioventricular canal, Proc. Staff Meet. Mayo Clin. 31:.513, 1956. Giraud, G., Latour, H., Puech, P., and Roujon, J.: Les formes anatomiques et les bases du diagnostic de la persistance du canal auriculo-ventriculaire commun, Arch. mal. coeur 50:909, 1957. Burch, G. E., and DePasquale, N.: The electrocardiogram and ventricular gradient in atria! septal defect, AM. HEART J. 58:190, 1959. Pryor, R., Woodwark, G. M., and Blount, S. G.: Electrocardiographic changes in atria! septal defects: Ostium secundum defect versus ostium primum (endocardial cushion) defect, AM. HEART J. 58:689, 1959. Arnetzenius, A. C., Nauta, J., Brom, A. G., and Snellen, H. A.: Vectorcardiogram and anatomy of atria! septal defect, Thorax 18:162, 1963. Cabrera, E., and Gasiola, A.: A critical reevaluation of systolic and diastolic overloading patterns, Prog. Cardiovas. Dis. 2:219, 1959. Schrire, V., and Vogelpoe!, L.: The role of the dilated pulmonary artery in abnormal splitting of the%econd heart sound, AM. HEART J. 63:501, 1962. Toscano-Barboza, E., and DuShane, J. M7.: Ventricular septal defect. Correlation of electrocardiographic and haemodynamic findings in 60 proved cases, Amer. J. Cardiol. 3:721, 1959. FouchC, R., Schrire, V., and Beck, I%‘.: The roentgenologic assessment of the degree of leftto-right shunt in secundum type atria1 septal defect, Am. J. Roentgenol. 89:254, 1963. Dalith, F., and Neufeld, H.: The radiological diagnosis of anomalous pulmonary venous connection. h tomographic study, Radiology 74:1, 1960. Kerley, P.: In Shanks, S. C., and Kerley, P., editors: Textbook of x-ray diagnosis, ed. 2, vol. 2, London, 1951, Lewis, pp. 68 and 404. Hilario, J., Lind, J., and Wegelius, C.: Rapid

55. 56.

57. 58.

59.

60.

61.

62.

63.

62. 65.

66. 67.

68.

sepal

dcfcct

277

biplane angiocardiography in the tetralogy of Fallot, Brit. Heart J. 16:109, 1954. Schrire, V., and Vogelpoel, L.: Personal data. Sambhi, M. P., and Zimmerman, H. A.: Pathologic physiology of Lutembacher’s syndrome, Am. J. Cardiol. 2:681, 1958. Bor, N., and Peters, R.: Double mitral apparatus or orifice, A.M.A. Arch. Path. 64:92, 1957. Braunwald, E., Lombardo, C. R., and Morrow, A. G.: Drainage pathways of pulmonary veins in atria! septnl defect, Brit. Heart J. 22:385, 1960. DuShane, J. W., Weidman, U’. I-I., Brandenburg, R. O., and Kirklin, J. W.: Differentiation of interatria! communications, Circulation 21:363, 1960. Snellen, H. A., and Albers, F. H.: The clinical diagnosis of anomalous pulmonary venous drainage, Circulation 6:801, 1952. Bruwer, A. J.: Posteroanterior chest roentgeuogram in two types of anomalous pulmonary venousconnection, J. Thoracic Surg. 32:119, i956. EsDino-Vela. 1.. Murad-Netto. S.. and RubioI.‘_ Alvarez, V.: L>Ifterential diagnosis between persistent atrioventricular canal and the combiuation of atria! and ventricular septal defe&s, Xtn. J. Cardiol. 6:.589, 1960. Hastreiter, A. R., Wennemark, J. R., Miller, 12. A., and Paul, M. H.: Secundum atria1 septal defects with congestive heart failure during infancy and early childhood, AM. HEART J. 64:467, 1963. Michaels, L., and Parkin, T. W.: nlild congecnital heart defects, J.A.M.A. 174:491, 1960. Griffiths, S. P.: Bacterial endocarditisassociated with atrial septal defects of the ostium secundum type, AM. HEART J. 61:543, 1961. McIlroy, M. B.: The clinical uses of oximetry, Brit. Heart J. 21:293, 1958. Morrow, A. G., Gilbert, J. W., Baker, R. Ii., and Perryman Collins, N.: The closure of atriai septal defects utilizing general hypothermia, J. Thoracic Surg. 40:777, 1960. Young, D. : Criteria for surgery in persistent common atrioventricular canal, Am. J. Cardiol. 12:80, 1963.