Definition
The classic form of cor triatriatum (meaning “heart with three atria”) may be defined as a rare cardiac malformation in which the left atrium (LA) is subdivided into dorsal and ventral chambers by a fibromuscular diaphragm, the dorsal (posterior) chamber receiving the pulmonary veins, the ventral (anterior) chamber giving rise to the left atrial appendage and leading to the mitral valve, and the communication between the dorsal and ventral chambers being large, small, or absent, depending on the size of the opening(s) in the subdividing diaphragm.
This typical form of cor triatriatum is also known as cor triatriatum sinistrum, meaning left-sided triatrial heart (Latin). There is also a right-sided form of triatrial heart, known as cor triatriatum dextrum (Latin). As will be seen, typical cor triatriatum sinistrum has stenosis of the common pulmonary vein, with a dorsal common pulmonary vein chamber ( Fig. 8.1 ), whereas typical cor triatriatum dextrum has a large and obstructive right venous valve between the caval compartment medially and the component of the right atrium (RA) laterally that leads to the tricuspid valve and the right atrial appendage.
Whenever the term cor triatriatum is used without further qualification, cor triatriatum sinistrum is meant.
It also should be understood that a heart with three atria (cor triatriatum) really does not exist, accurately speaking. These are hearts with three chambers at the atrial level, but not with three complete and separate atria.
Instead, cor triatriatum denotes subdivided atria: subdivided LA (cor triatriatum sinistrum, see Fig. 8.1 ), and subdivided RA (cor triatriatum dextrum).
Let us first consider cor triatriatum sinistrum, usually referred to for brevity simply as cor triatriatum or subdivided LA.
Cor Triatriatum Sinistrum
Much has been written about cor triatriatum sinistrum. The first clear-cut description of this anomaly was by W.S. Church in 1868. His patient (Jane D) was a 38-year-old widow, the mother of four children. The opening in the subdividing diaphragm was {4/10} inch (10 mm) by {7/10} inch (18 mm). Two woodcut drawings depict cor triatriatum persuasively ( Fig. 8.2 ).
The references are presented chronologically so that the interested reader can gain an appreciation of how understanding of this anomaly has grown over time.
It has long been known that cor triatriatum is one of the rarest forms of congenital heart disease. In 1967, Keith, Rowe, and Vlad encountered 7 patients with cor triatriatum in a series of 6647 patients with congenital heart disease, cor triatriatum constituting only 0.105% of patients with congenital heart disease in their extensive experience. Cor triatriatum was isolated in 5 patients and associated with other congenital heart disease in 2 patients.
My intense interest in cor triatriatum began in 1963, when I had the privilege of working with Dr. Maurice Lev in the Congenital Heart Disease Research and Training Center at the Hektoen Institute for Medical Research in Chicago, Illinois. This study led to a paper with Dr. Ignacio Corsini that was published in 1969.
Why did Dr. Lev assign us this project? A little background will be helpful. The basic question was: What really is cor triatriatum anatomically and developmentally? At that time (1963–1965), there were two warring hypotheses concerning what cor triatriatum is: (1) stenosis of the common pulmonary vein or (2) an anomaly of septum primum (the flap valve of the foramen ovale).
We very carefully studied a series of 13 postmortem cases of cor triatriatum, but initially were unable to decide which (if either) morphogenetic hypothesis was correct. The pathologic anatomy strongly suggested that the dorsal (posterior) chamber was indeed the stenotic common pulmonary vein ( Figs. 8.1 to 8.4 ). However, the intra-atrial subdividing diaphragm always was confluent with the septum primum (see Figs. 8.4 and 8.5C ), suggesting that the septum primum also must be involved in the morphogenesis of cor triatriatum.
Looking back into the literature, we found that these two conflicting developmental hypotheses went back almost to the discovery of cor triatriatum. Church, who in 1868 first described the malformation that would later come to be known as cor triatriatum, expressed no hypothesis concerning the pathologic anatomy and its developmental basis. However, in 1881, Fowler suggested that this anomaly resulted from overgrowth of the valve of the foramen ovale. Indeed, septum primum is an integral part of the subdividing diaphragm within the LA both grossly and histologically ( Fig. 8.6 ).
In 1903, Griffith proposed that this anomaly represents failure of incorporation of the common pulmonary vein. In his own words, he wrote that this malformation appears to represent “a failure in the complete amalgamation of that part of the auricle which is said to be formed from the confluent portions of the pulmonary veins and that derived from the left-hand division of the common auricle of the embryonic heart.”
Griffith added, “I think it must depend on some such anomaly of development as has been suggested by Dr. Martin and myself.”
What had happened is as follows. Griffith presented his first case of this malformation to the Anatomical and Physiological Society of London in 1896, where he first proposed the concept of failure of incorporation of the common pulmonary vein. However, this hypothesis did not meet with the approval of the meeting so he dropped it temporarily. After the meeting, while preparing his abstract, he read Fowler’s paper and concluded that Fowler was right, that is, that this anomaly represents abnormal displacement of the septum primum due to abnormal streaming of the blood within the embryonic atria.
Then at the 1899 meeting of the same society, Martin presented his case of the malformation, which was essentially identical to Griffith’s case, and Martin also expressed his support for Griffith’s concept of malincorporation of the common pulmonary vein.
So, when Griffith presented his second case of this anomaly in 1903, he returned to his original malincorporation concept because there was no evidence of acquired postnatal pathologic change. He added, “Perhaps, when the development of the pulmonary veins and their manner of junction with the left auricle is more fully understood, the explanation may become less uncertain.” So, in presenting his second case, Griffith stuck to his guns (failure of incorporation), although fully understanding that much remained to be learned concerning incorporation of the pulmonary veins into the LA.
Thus, by 1903, two main morphogenetic hypotheses concerning this anomaly had emerged: (1) an abnormality of the septum primum, Fowler in 1881; and (2) malincorporation of the common pulmonary vein, Griffith , in 1896 and 1903, and Martin in 1899.
In 1905, Borst published another definite case of this malformation and introduced the term cor triatriatum . Borst also proposed a third morphogenetic hypothesis: that the pulmonary vein develops to the right of the septum primum, instead of to the left of the septum primum, which he thought was normal. Rightward malposition of the common pulmonary vein relative to the septum primum appeared to be supported by some cases of cor triatriatum in which the common pulmonary vein chamber lies predominantly to the right of the septum primum (see Figs. 8.4 and 8.5C ). However, in other cases, the common pulmonary vein chamber lies predominantly to the left of the septum primum (see Figs. 8.2C and 8.3 ). Both in Fowler’s and Borst’s hypotheses, the subdividing diaphragm was thought to be the septum primum.
In 1949, Loeffler found that the septum primum is related normally to the septum secundum in cor triatriatum. Consequently, he decided that the subdividing diaphragm cannot be an abnormally located septum primum. Since that time, most investigators have accepted the hypothesis of malincorporation of the common pulmonary vein that was first published in 1903 by Griffith. However, Loeffler was well aware that the more basic question remained unanswered, namely: Why does the common pulmonary vein fail to incorporate normally into the LA in cor triatriatum? He suggested that malincorporation of the common pulmonary vein into the LA is “caused in all probability by a disturbance of the normal growth of the posterior wall of the left atrium.” He concluded that the subdividing diaphragm is the abnormal posterior wall of the primitive LA.
However, not all investigators found the malincorporation hypothesis persuasive. As Sawyer et al pointed out in 1957, this hypothesis fails to explain those cases in which the foramen ovale or fossa ovalis has been reported to be located in the medial wall of the dorsal (posterior) chamber. If the malincorporation hypothesis were correct, one would expect the foramen ovale (or fossa ovalis) always to open into (or to be adjacent to) the primitive LA (the ventral chamber). This problem is exemplified by Fig. 8.7 . A small opening exists between the common pulmonary vein chamber and the RA in the general region of the foramen ovale or fossa ovalis.
In view of the aforementioned confusion regarding what cor triatriatum really is anatomically and embryologically, and our inability to decide which (if any) of these three contending hypotheses is correct based on pathologic anatomic examination, we decided to undertake a study of the development of the pulmonary vein and atrial septum in 83 human embryos from the Minot Collection of Harvard Medical School. Then we attempted to correlate the pathologic anatomic findings in these 13 postmortem cases of cor triatriatum with the embryologic findings in 83 normal human embryos.
Embryology
The youngest human embryo in which we were able to identify the common pulmonary vein with certainty had an estimated age since ovulation of 27 days ( Fig. 8.8 ). In this horizontal plane section, note that the common pulmonary vein is an essentially midline structure and that it communicates with a still undivided common atrium. The right and left lung buds are well seen. This sinus venosus is right-sided and opens into the common atrium. The common atrium communicates with the ventricle of the bulboventricular loop via the common atrioventricular (AV) canal. The superior (ventral) and the inferior (dorsal) endocardial cushions of the common AV canal are well seen. The endocardial cushions of the bulbus cordis are seen lying to the right of the ventricle, as one would expect with a D-bulboventricular loop. In the magnification of the common pulmonary vein (see Fig. 8.8B ), the erythrocytes are prominent because they are nucleated at this stage of development, resembling normoblasts of later developmental stages.
Histologically, we were unable to tell whether the common pulmonary vein grows out in a dorsal (or posterior) direction from the common atrium into the lung buds via the dorsal mesocardium, whether the common pulmonary vein grows in a ventral (or anterior) direction from the lung buds into the common atrium via the dorsal mesocardium, or whether the common pulmonary vein grows in both directions—dorsally from the common atrium and ventrally from the lung buds—to make contact in the dorsal mesocardium (the broad and short connection between the common atrium and the lung buds). Our data did not clarify the direction of growth of the common pulmonary vein. Consequently, we can make no comment on this point from our data, except to say that three possibilities exist, as mentioned earlier.
By 33 days of age, many changes have occurred in the normal human embryo ( Fig. 8.9 ). In this horizontal plane section (see Fig. 8.9A ), note that the common pulmonary vein lies immediately to the left of a prominent mass of sinus venosus fibrous tissue. The common pulmonary vein has enlarged, and it remains a midline structure ventral to the midline esophagus that lies between the developing right and left lungs. The sinus venosus (right horn) lies to the right, and a relatively small left superior vena cava (LSVC; left sinus horn) lies to the left. The right venous valve is seen, and the right and left atria are demarcated.
In a horizontal plane section from the same embryo 128 μ above that shown in Fig. 8.9A , note that the septum primum is now well formed (see Fig. 8.9B ). The septum primum lies above the common pulmonary vein, both of which are essentially midline structures. The septum primum and the left venous valve both have grown upward from the mass of venous or sinus venosus fibrous tissue shown in Fig. 8.9A . The space between the septum primum and the left venous valve is known as the interseptovalvular space (see Fig. 8.9B ).
In Fig. 8.9B , note that the right horn of the sinus venosus is seen, as are the right and left venous valves—the leaflets of the body’s largest venous valve. The small LSVC is again noted.
By 35 days of age in the normal human embryo, a horizontal plane section shows that incorporation of the common pulmonary vein into the LA is beginning ( Fig. 8.10 ). Note the trifurcation of the common pulmonary vein in the dorsal mesocardium. The common pulmonary vein still lies below the septum primum and immediately to the left of the prominent mass of sinus venosus tissue from the right sinus horn. As frontal plane sections show (vide infra), the septum primum grows upward from the left side of this mass of sinus venosus tissue and the left venous valve grows upward from the right side of this platform of sinus venosus tissue. The lungs and the midline esophagus are both developing. The right-sided sinus venosus, the right venous valve, the RA, and the LSVC are also noteworthy (see Fig. 8.10 ).
By 38 days of age in the normal human embryo ( Fig. 8.11 ), incorporation of the common pulmonary vein and its branches into the LA is progressing. Note that the common pulmonary vein now lies to the left of the septum primum instead of beneath the septum primum, as in earlier normal stages. Note that the septum primum and the left venous valve are fused at their bases. In this embryo, the left superior vena cava LSVC is still quite large (see Fig. 8.11 ).
By 63 days of age in the normal human embryo ( Fig. 8.12 ), this horizontal plane section shows that the common pulmonary vein is well incorporated into the LA; that is, the region of the common pulmonary vein is now so wide that it is no longer distinguishable as the common pulmonary vein because it has become incorporated as part of the dorsal wall of the LA. The right pulmonary vein enters the LA just to the left of and posterior to the septum primum. The left pulmonary vein has a separate ostium into the LA, further to the left. The fact that both pulmonary venous branches—the right and left pulmonary veins—have separate openings into the LA indicates that the common pulmonary vein has been incorporated into the LA.
However, at 63 days of age, incorporation of the pulmonary venous branches is incomplete. Ultimately, each pulmonary vein is incorporated into the LA up to just beyond the primary division of each branch. Postnatally, this is why there normally appear to be two left pulmonary veins (from the left upper and lower lobes of the lung), and two or three right pulmonary veins (from the right upper, middle, and lower lobes of the lung). In Fig. 8.12 , both pulmonary venous ostia appear to be widely patent (nonobstructive). Note that the LSVC is now diminutive, almost a ligament of Marshall (see Fig. 8.12 ). The pulmonary veins remain midline structures; note the relation of the pulmonary veins to the midline trachea (see Fig. 8.12 ). The pulmonary parenchyma has developed considerably, as has the left aortic arch. Parts of the septum secundum and the right venous valve are also noteworthy (see Fig. 8.12 ).
Frontal plane sections are also very helpful in understanding the normal development of the common pulmonary vein relative to that of the atrial septum ( Fig. 8.13 ) When the normal human embryo is 33 days of age (similar in age to Fig. 8.9 , which shows horizontal plane sections), one notes the prominent platform of sinus venosus tissue. From its left side, the septum primum grows upward. From its right side, the left venous valve grows upward. The right venous valve lies to the right of the inferior vena cava (IVC). Note that the common pulmonary vein is located immediately to the left of the base of the large mass of sinus venosus (fibrous) tissue. In somewhat greater detail, the common pulmonary vein runs adjacent to and partly beneath the left side of the overhanging mass of sinus venosus tissue. The tracing of this slide (see Fig. 8.13A ), seen in Fig. 8.13B , makes these relationships clearer.
Thus, at 33 days of age in the normal human embryo, the common pulmonary vein lies beneath the septum primum and the sinus venosus tissue from which the septum primum develops (see Fig. 8.13A–B ). In other words, the common pulmonary vein is located as medially and as inferiorly as possible within the LA. This is the normal position of the common pulmonary vein at 33 days of age (see Fig. 8.13 ). To indicate that this is not just one fluke section, frontal plane sections from the same 33-day-old embryo are shown 48 μ dorsal to Fig. 8.13A (see Fig. 8.13C ) and 40 μ dorsal to Fig. 8.13C (see Fig. 8.13D ). The small common pulmonary vein is still directly beneath septum primum and the left side of the mass of sinus venosus tissue from which the septum primum develops (see Fig. 8.13C–D ).
The midline and inferior location of the common pulmonary vein in the normal 33-day-old human embryo is confirmed in a sagittal section of another embryo ( Fig. 8.14 ). Note that the midline location of the common pulmonary vein beneath the prominent mass of right horn sinus venosus tissue is corroborated by finding the trachea and the esophagus both cut longitudinally in the same section (see Fig. 8.14 ).
We are stressing the medial and inferior location of the common pulmonary vein at this early stage (27 to 33 days of age) because this is not how these relationships are conventionally presented. Instead, the common pulmonary vein usually is shown to appear well to the left of the septum primum and much higher (more cephalad) ( Fig. 8.15 ). As shown previously (see Figs 8.7 to 8.14 ), this is not where we found the common pulmonary vein to appear. As will be seen, correction of this error makes it possible to understand the morphogenesis of cor triatriatum sinistrum.
But before we turn to a consideration of abnormal development, we must complete the normal development of the pulmonary vein and septum primum ( Fig. 8.16 ). When the embryo is 56 days of age, note that the platform of sinus venosus or venous fibrous tissue has largely disappeared (compare Fig. 8.16A with Fig. 8.13 ). Instead, by 56 days of age, this mass of fibrous tissue has been replaced by its progeny. On the left side, the septum primum has grown upward to the left of the septum secundum, and on the right side, this less well-developed left venous valve has also grown upward (see Fig. 8.16A ). The space between the septum primum to the left and the left venous valve to the right is the interseptovalvular space (see Fig. 8.16B ).
Note that the septum primum and the left venous valve are both directly continuous with the left wall of the IVC (see Fig. 8.16 ). The right venous valve, that is, the Eustachian valve, is directly continuous with the right wall of the IVC.
The sinoatrial valve, at the junction of the sinus venosus with the RA, is the largest venous valve in the body (see Fig. 8.15 ). It is conventionally thought of as being incompetent; that is, it does not prevent regurgitation from the RA into the IVC or SVC.
It was during this study of human embryos that we came to understand an alternative view:
- 1.
The left side of the sinoatrial valve is really bifid; it is composed of two leaflets—the septum primum to the left and the left venous valve to the right—that are confluent at their bases (see Figs. 8.13 and 8.16 ). Both components of the left venous valve mechanism arise from the same platform of sinus venosus tissue (see Fig. 8.13 ).
- 2.
Both components of the left venous valve mechanism grow upward (cephalad) (see Figs. 8.13 and 8.16 ), not downward (caudad), as is conventionally said (see Fig. 8.15 ). The erroneous view that the septum primum grows downward is due to misorientation of the heart in space. For example, Fig. 8.15 is easily mistaken for frontal plane views of the heart, in which the septum primum appears to grow downward. But in the embryo, the ventricles do not lie below the atria. Instead, the ventricles lie in front of (ventral to) the atria. As soon as one realizes that Fig. 8.15 is a diagrammatic (horizontal) plane reconstruction (not a frontal plane reconstruction), then one understands that the septum primum is really growing upward (not downward).
- 3.
We realized that another important error in the conventional account of atrial septation is as follows. The septum primum does not grow down to close the ostium primum (see Fig. 8.15 ). Instead, the septum primum grows upward behind the ostium primum. The septum primum does not close the ostium primum. Instead, the ostium primum normally is closed by the endocardial cushions of the AV canal. Persistence of the ostium primum really is an endocardial cushion defect. An ostium primum defect is also correctly known as an incomplete form of common AV canal (or a partial AV septal defect).
- 4.
The ostium secundum is the space above the upper edge of the upwardly growing septum primum (see Fig. 8.16A ). The ostium secundum is not formed by the timely coalescence of multiple small fenestrations within the septum primum. It should be added that there are small fenestrations within the septum primum, just as there are within other venous valves.
- 5.
The septum primum really is a venous valve—the main component of the left venous valve apparatus. Understood in this way, the sinoatrial valve, the largest venous valve in the body, is not normally incompetent. This venous valve, because of the septum primum, is normally competent between the LA on the one hand and the RA and the venae cavae on the other.
Against the background of the previously mentioned improved understanding of the normal development of the pulmonary veins and the atrial septum, we are now ready to consider the pathologic anatomy of cor triatriatum sinistrum.
Pathologic Anatomy
Based on our study of 13 postmortem cases of cor triatriatum sinistrum from three different medical centers that was published in 1969, the salient finds were as follows :
Sex: Males = 12; females = 0; unknown, 1. The male-to-female ratio = 12:0. Thus, although this is a small series, the findings suggest that there may well be a strong male preponderance in cor triatriatum sinistrum.
Age at Death: In 12 cases (unknown in 1), mean 2.4 ± 5.8 years, ranging from 3 days to 20.8 years. The median age at death was 8.5 months.
Heart Sidedness: Left-sided in 12 of 13 cases (92%) and right-sided in 1 (8%)—a patient with secondary dextrocardia due to hypoplasia of the right lung (most marked of the right middle lobe).
Heart Size: Enlarged in all 13 cases (100%) (see Fig. 8.2A ).
Right Atrium: Hypertrophied and enlarged in all (100%) (see Fig. 8.2B ). The right atrial septal surface usually appeared abnormal. For example, in the case presented in Fig. 8.2 , the right atrial septal surface is almost completely smooth, there being no limbic ledge formed by the septum secundum and virtually no demarcation between the septum primum and the septum secundum (see Fig. 8.2B ). When obliquely probe patent, as in 8 of 13 cases (62%), the foramen ovale usually was distinctly smaller than normal, apparently because of the upward protrusion of the dorsal common pulmonary vein chamber (see Fig. 8.2D ). By bulging upward, the common pulmonary vein chamber encroached on the foramen ovale from below and behind, tending to narrow or close it.
Atrial Septum: Intact, 4 (30.8%); patent foramen ovale, 8 (61.5%); and secundum atrial septal defect (ASD), 1 (7.7%).
Tricuspid Valve: Enlarged, 11 (84.6%); normal, 1 (7.7%); and tricuspid atresia, 1 (7.7%). The tricuspid valve was usually enlarged because of associated right ventricular hypertrophy and enlargement. In the 1 patient in whom the tricuspid valve was found to be normal in size (compared with normal controls), the right ventricle (RV) was thick-walled and small-chambered (and the right ventricular outflow tract and pulmonary valve were enlarged).
Ventricular Septum: Intact, 10 (76.9%); and ventricular septal defect (VSD), 3 (23.1%).
Right Ventricle: Right ventricular hypertrophy and enlargement, 11 cases (84.6%); hypoplastic, 1 (7.7%); and thick-walled and small-chambered, 1 (7.7%).
Pulmonary Valve: Enlarged, 10 (76.9%); and hypoplastic, 3 (23.1%).
Mitral Valve: Hypoplastic, 6 (46.1%); normal, 5 (38.5%); enlarged, 1 (7.7%); and absent, 1 (7.7%).
Left Ventricle: Hypoplastic, 5 (38.5%); normal, 5 (38.5%); enlarged, 2 (15.3%); and absent, 1 (7.7%).
Aortic Valve: Hypoplastic, 5 (38.5%); normal, 6 (46.1%); enlarged, 1 (7.7%); and aortic atresia, 1 (7.7%).
The Anomaly
The opened left heart chambers (see Figs. 8.1 and 8.2C–D ) showed the following :
- 1.
The common pulmonary vein chamber was stenotic, dilated, and hypertrophied. It was dorsal (posterior) to, and obliquely inferior to the ventral (anterior) left atrial chamber.
- 2.
The fibromuscular diaphragm was oriented obliquely from posterosuperiorly to anteroinferiorly (see Figs. 8.1 and 8.2C–D ).
- 3.
The number of openings in the subdividing diaphragm were: 1 in 9 cases (69.2%); 2 in 3 patients (23.1%); and none in 1 (7.7%).
- 4.
The size of the openings in the diaphragm (mm in diameter): 0 mm, 1 case (1/16 = 6.25%); 0.5 mm, 2 cases (12.5%); 1 mm, 4 cases (25%); 2 mm, 3 cases (18.75%); 3 mm, 5 cases (31.25%); and 5 mm, 1 case (6.25%). The mean diameter of the opening(s) in the intra-atrial diaphragm was 1.9 ± 1.3 mm, ranging from 0 to 5 mm. The median diameter of the opening was 2.0 mm.
- 5.
The location of the opening in the intra-atrial diaphragm was a short distance behind the posteromedial commissure of the mitral valve (see Figs. 8.1 and 8.2C–D ). In other words, the location of the opening in the subdividing diaphragm was very inferior and very medial within the LA, that is, extremely close to the initial location of the common pulmonary vein in the early human embryo at 33 days of age (see Figs. 8.9 and 8.13 ), before the normal incorporation of the common pulmonary vein into the LA.
- 6.
The septum primum was always in direct fibrous continuity with the subdividing intra-atrial diaphragm (see Fig. 8.4 ) . It is illuminating to note that the continuity between septum primum and the diaphragm in cor triatriatum (see Fig. 8.4 ) appears essentially identical to the continuity between septum primum and the dorsal wall of the LA in totally anomalous pulmonary venous connection (TAPVC) ( Fig. 8.17 ). It should be understood that the LA in TAPVC is the normal LA, minus its pulmonary venous component.
These observations (compare Figs. 8.4 and 8.17 ) strongly suggest that the subdividing diaphragm in cor triatriatum is composed of the wall of the LA ventrally and the wall of the unincorporated stenotic common pulmonary vein dorsally (see Fig. 8.1 and 8.2D ).
