The anomaly now known as the tetralogy of Fallot (TOF) was first described, insofar as is known, by Niels Stensen in 1671. He was also known in Latin as Nicolaus Steno.
Stensen (1638–1686) was a Danish anatomist and naturalist from Copenhagen. He is said to have given up his medical career for the church, becoming the Bishop of Titiopolis in 1667. However, he remained a devoted anatomist. Four years later, in 1671, he published the first known case of tetralogy. His other famous paper about the anatomy and function of the parotid duct— Stensen’s duct —did not appear until 1682. He also described the principles leading to the formation of the Earth’s crust and the occurrence of fossils. Thus, Stensen was a bishop and an anatomist, with the expertise and the wide-ranging interests of a 17th-century naturalist.
Stensen’s Case. , Stensen’s patient was a malformed fetus. The gestational age was neither stated nor estimated. The salient findings were as follows: a cleft palate; right-sided hare lip; all fingers of the left hand were united by a common skin fold; the third finger of the left hand was shortest; the left thumb was free—not united with the left fingers; the sternum was split; the heart, liver, spleen, right kidney, and most of the intestines were outside of the thorax and abdomen; these organs were uncovered; the lungs were in the thorax; the kidneys were lobulated; and the adrenals were large and triangular.
Thus, this fetus had ectopia cordis, thoracic and abdominal—with ectopy of much more than the heart. The diaphragm and the brain were not described.
Regarding the heart, the pulmonary artery was much narrower than the aorta. The ductus arteriosus was absent. There was a subaortic ventricular septal defect (VSD) and an overriding aorta.
I think that this fetus with multiple congenital anomalies including ectopia cordis probably did have what we now call tetralogy of Fallot with pulmonary outflow tract atresia.
Early Pre-Fallot Reports
Edouard Sandifort (1742–1814), a Dutch physician, described a patient with tetralogy in 1777. Known as “the blue boy,” this patient died at 124⁄12 years of age. Clinically, he had been thought to have asthma. However, his parents suggested an autopsy, which revealed a congenitally malformed heart. The heart description sounded like tetralogy. Again there was no ductus arteriosus or ligamentum arteriosum. Sandifort thought that the congenital heart malformation of the blue boy resembled that of Stensen’s patient. ,
William Hunter (1718–1783) was the elder brother of his more famous young brother John, who was an eminent surgeon. William Hunter was a Scottish physician from the University of Glasgow, who moved to London where he became a leading obstetrician and obstetrical anatomist. In 1784, three cases of congenital heart disease were published 1 year following the author’s death. Hunter’s Case 2 was a 13-year-old boy with tetralogy and blue spells.
Numerous other case reports followed over the next century. (The references cited are not a complete list.)
What, then, was so special about the serialized reports of Etienne-Louis Arthur Fallot ( Fig. 20.1 ) in Marseille Médical of 1888? Parenthetically, his friends called him Arthur, which is how he signed his published work. Just listen to a literal translation of his first sentence: ,
One of the happy hazards which comes sometimes to procure for the clinician precious occasions to instruct himself, has in the space of several years, made to pass beneath our eyes three cases of a rare and curious malady, on the pathologic anatomy of which reigns, even in the informed medical public, grave errors and singular incertitudes, we have had the occasion to observe during their life and at autopsy following their death, three subjects afflicted with the malady called cardiac cyanosis, and it would be according to us, much more correct to designate exclusively under the name of the blue malady.
In Fallot’s late-19th-century prose, I hear similarities with the elegance and charm of Charles Dickens and Sir Arthur Conan Doyle.
But there was much more to Fallot than elegance and charm. There was also substance and clinical relevance.
He described the tetralogy, the four anatomic features that occurred together in his three patients:
pulmonary outflow tract obstruction, stenosis, or atresia;
a subaortic VSD;
aortic overriding; and
right ventricular hypertrophy.
He emphasized that cyanosis was not caused by a patent foramen ovale, as many had supposed.
Fallot proposed that these four interrelated malformations were caused by an intrauterine pathologic process involving the pulmonary valve and the subpulmonary infundibulum. In other words, Fallot understood that one pathologic process underlay this nonrandom and interrelated tetrad of anomalies.
Fallot called this group of four malformations la maladie bleue (the blue malady).
It was Maude Abbott of Montreal, Canada who coined the term tetralogy of Fallot in 1924.
Thus, in 1888, Fallot understood that this tetralogy was basically just one anomaly involving the pulmonary valve and the subpulmonary infundibulum—not four unrelated malformations that occurred together only by chance.
We independently reached a very similar conclusion in 1970. We proposed that the TOF results from underdevelopment of the subpulmonary infundibulum in three dimensions ( Figs. 20.2 to 20.8 ). The classical tetralogy consists of the sequelae of an underdeveloped, low-volume, and hence obstructive subpulmonary infundibulum. The pulmonary valve is the “back door” of the subpulmonary infundibulum. This helps to explain why the pulmonary valve is frequently, but not universally, involved in right ventricular outflow tract obstruction. By contrast, the subpulmonary infundibulum is always abnormal in TOF.
Hence, the tetralogy of Fallot is basically the “monology of Stensen.” The tetralogy is really just one anomaly (a monology), that is, three-dimensional underdevelopment of the subpulmonary infundibulum and the sequelae thereof, that was first described by Stensen.
The concept of the monology of Stensen is intended to deepen morphogenetic and anatomic understanding. We are not trying to change diagnostic terminology.
Compare the normal morphologically right ventricle ( Fig. 20.9 ) with the right ventricle in TOF ( Figs. 20.2 to 20.8 ). Normally, the subpulmonary infundibulum forms a conal septum (or an infundibular septum) that flows into the parietal band ( Fig. 20.9 ). The infundibular septum and parietal band form a crista supraventricularis (or supraventricular crest) that arches over the septal band, the ventricular septum, the tricuspid valve, and the right ventricular sinus (body, or inflow tract) ( Fig. 20.9 ). Normally, the subpulmonary infundibulum fills the space above the septal band, the ventricular sinus septum, and the tricuspid valve ( Fig. 20.9 ).
But abnormally, when the subpulmonary infundibulum is hypoplastic in three dimensions, the space above the septal band and the ventricular septum remains wide open ( Figs. 20.3 to 20.8 ), resulting in a subaortic VSD. The subpulmonary infundibular septum remains abnormally leftward, anterior, and superior. In other words, the subpulmonary infundibular septum fails to move normally in a rightward, posterior, and inferior direction.
This results not only in a large subaortic VSD, in a typical case. It also results in subpulmonary infundibular outflow tract obstruction because the infundibular septum, the “floor” of the infundibular outflow tract, is abnormally close to the infundibular free wall, the “roof” of the infundibular outflow tract. Hypoplasia of the subpulmonary infundibulum in three dimensions (3D) results in a low-volume and hence obstructive subpulmonary infundibulum that is either stenotic ( Figs. 20.2 to 20.7 ) or atretic ( Fig. 20.8 ).
The low-volume, obstructive subpulmonary infundibulum results in right-to-left shunting through the large VSD into the left ventricle and the aorta, resulting in cyanosis in untreated patients with TOF ( Fig. 20.3 ). This is why in 1777 Sandifort’s patient, “the blue boy,” was blue, and why in 1888, Fallot wanted to call the anomaly that he was describing the blue disease (“la maladie bleue”). However, by 1924, it was clear to Abbott that this tetralogy was not the only blue disease; hence Abbott’s proposal: the tetralogy of Fallot. Abbott was also aware of transposition of the great arteries.
The understanding that TOF is only one malformation and its sequelae has important diagnostic and surgical consequences.
Diagnostically, it was appreciated that if a patient has a high pulmonary artery wedge pressure indicating left atrial hypertension (for example, because of cor triatriatum, or congenital mitral stenosis), it is nonetheless possible to make the diagnosis of TOF. It used to be thought that if there were no demonstrable gradient on catheter pull-back from the main pulmonary artery into the right ventricle, TOF could not be present. “No pull-back gradient, no TOF” used to be a cath lab dictum. But we learned that left atrial obstruction could produce pulmonary artery hypertension that in turn could mask significant infundibular obstruction, that is, that could mask the coexistence of TOF.
When pulmonary hypertension coexists for any reason (congenital or acquired), how does one make the diagnosis of coexistent TOF?
The answer is almost absurdly simple: Look at the subpulmonary infundibulum (angiocardiographically, or by any accurate noninvasive technique). Is the infundibulum hypoplastic and obstructive-looking, or not?
The importance of understanding that the TOF basically is the monology of Stensen (obstructive hypoplasia of the subpulmonary infundibulum and its sequelae) is even more important surgically than diagnostically. Gone was the old-fashioned repair of TOF. It began with a long, low, J-shaped or hockey-stick–shaped right ventriculotomy, to provide good visualization of the VSD. This was followed by extensive myocardial resection of the parietal band and of the septal band, with thinning of the right ventricular free wall. Much of this septal and free wall myocardial resection was proximal or upstream to the infundibular and valvar and pulmonary arterial obstructions. This old-fashioned surgical approach to the repair of TOF often led to low cardiac output and death postoperatively. The thinned right ventricular free wall often became a paradoxing right ventricular outflow tract aneurysm. The causes of death were right ventricular iatrogenic infarction, or unrelieved right ventricular outflow tract obstruction because of fear of transannular patches, or both.
Once the foregoing , was understood, our surgical approach was transformed and our results improved dramatically. The infundibulotomy became as short as possible. Right ventricular myocardial resection was essentially abandoned altogether. Castañeda and his colleagues, who led this surgical transformation, found that in young infants with TOF, there really is very little muscle to excise. If one operates early enough, secondary postnatal myocardial right ventricular hypertrophy has not as yet occurred. The use of transannular patches without myocardial resection achieved absence of right ventricular outflow tract obstruction with minimal right ventricular trauma.
With this new surgical approach, we realized that TOF could be successfully repaired at any postnatal age—in the newborn period (the first 30 days), or in infancy (the first year of life).
This new therapeutic approach became known as the Castañeda doctrine:
Repair TOF whenever the patient needs it, in the newborn period if necessary.
One operation is better than two. Avoid palliative surgery such as Blalock-Taussig shunts, whenever possible.
How Common is Tetralogy of Fallot?
In a series of 2965 patients selected at random in the cardiac pathology database of the Cardiac Registry of Boston Children’s Hospital and Harvard Medical School, there were 407 cases of TOF (14%) ( Table 20.1 ). TOF was the fifth most common type of congenital heart disease in our cardiac pathology database, right behind transposition of the great arteries (442 cases, 15%, Table 20.1 ).
What are the Situs of the Main Cardiac Segments in TOF?
Are the atria, the ventricles, and the great arteries always in situs solitus (i.e., normal, noninverted anatomic organizational patterns) in TOF? Almost always, but not always ( Table 20.2 ).