In the accompanying manuscript, Perdreau and colleagues,Reference Perdreau, Houyel and Baruteau ¹ from Hopital Marie Lannelongue, in Paris, offer important insights that should contribute markedly to our understanding of the morphogenesis of the lesions that afflict the ventricular outflow tracts. In the past, as the authors explain, those invoking the flow theories developed by Rudolph and his colleaguesReference Rudolph, Heymann and Spitznas ² had presumed that aortic coarctation could not co-exist with tetralogy of Fallot. It was thought that, if the flow favoured the aorta, as would be the case in lesions with hypoplasia of the subpulmonary outflow tract, then it would not be possible for obstructions to develop within the systemic extrapericardial channels. And it was, indeed, the case that such narrowings were hardly ever encountered in large series of patients with tetralogy. Surprisingly, again as explained by the authors, rare patients with tetralogy were found also to exist with aortic coarctation. Prior to the current investigation, however, it had not been noticed that, when the obstruction was found in a left-sided aortic arch, it occurred at the isthmus, in other words in the setting of so-called “juxtaductal” coarctation. In contrast, when the narrowing was found in patients with a right-sided aortic arch, the obstructive lesion, rather than being the typical isthmic variant of coarctation, was produced by a segment of aortic arch showing tubular hypoplasia between the right common carotid and right subclavian arteries. As the authors again explain, this variant can be considered a “forme fruste” of interruption of the aortic arch between these vessels, so-called interruption type B within the categorisation provided by Celoria and Patten.Reference Celoria and Patton ³

This observation is itself of great significance, since it shows that obstructive lesions within the aortic arch can behave in syndromic fashion, and are presumably driven by different genetic pathways. Equally important, however, is the recognition by the Parisian group that it is less than helpful to consider these lesions as being “conotruncal”. To the best of my knowledge, there is no generally accepted, yet scientifically accurate, definition of a “conotruncal defect”. Some include congenitally corrected transposition within this grouping,Reference Frank, Dillman, Parich, Mueller, Kazerooni, Bell and Attili ⁴ yet the predominant anomaly in this lesion is the discordant nature of the atrioventricular connections. This feature reflects abnormal ventricular looping, as opposed to maldevelopment of the ventricular outflow tracts. It has yet to be explained why discordant ventriculo-arterial connections should usually, but not always, accompany the discordant atrioventricular connections. More importantly, again to the best of my knowledge, there are no investigators who include arterial valves with two or four leaflets as “conotruncal anomalies”. The arterial roots, however, develop and separate from one another within the central component of the embryonic outflow tract. If any lesions are to be considered “conotruncal”, then it surely should be those that produce congenital malformations of the arterial valves and their supporting sinuses?

The problems with the definition of “conotruncal anomalies” can be traced back to similar problems that continue to surround the definition of the embryonic “conus” as opposed to the “truncus”. When Kramer introduced these terms in 1942,Reference Kramer ⁵ his investigation represented a major step forward in terms of our understanding of cardiac development. In that seminal work, KramerReference Kramer ⁵ argued that new terms were needed to describe this part of the developing heart, since consensus had still to be reached on the optimal way of describing its outflow portion. Despite the current widespread use of his suggested terms “conus” and “truncus”, I would argue that achieving the hoped-for consensus is still proving elusive. This is because there is no agreement as to whether the arterial valvar leaflets, and their supporting sinuses, develop with the “conus”, or are part of the “truncus”. Those using the term “conus” in the setting of congenitally malformed hearts usually use the word to describe the infundular musculature which supports the valvar leaflets. And “truncus”, if used, would intuitively be considered to describe the intrapericardial arterial trunks, although there is some uncertainty as to whether these components are derived from the embryonic aortic sac.Reference Restivo, Piacentini, Placidi, Saffirio and Marino ⁶ Uncertainty is then exaggerated by those who describe a “level” for the arterial valves.Reference Bartelings and Gittenberger-de Groot ⁷ In reality, the arterial valvar leaflets, along with their supporting arterial sinuses, occupy a significant length of the definitive outflow channels.Reference Anderson, Chaudhry, Mohun, Bamforth, Hoyland, Phillips, Webb, Moorman, Brown and Henderson ⁸

In my opinion, therefore, it makes more sense to describe the embryonic outflow tract as possessing three, rather than two, components. These parts can readily be recognised in both human and mouse embryos.Reference Anderson, Chaudhry, Mohun, Bamforth, Hoyland, Phillips, Webb, Moorman, Brown and Henderson ^{8 ,} Reference Sizarov, Lamers, Mohun, Brown, Anderson and Moorman ⁹ They can readily be described as being proximal, intermediate, and distal. The appearance of the intercalated cushions, initially recognised and named by Kramer in his stellar investigation,Reference Kramer ⁵ along with recognition that the outflow tract is bounded distally by the pericardial reflections, subsequently makes it possible anatomically to define the borders of these three component parts. We now know, again as recognised by the authors, that cells derived from the neural crest are necessary not only to produce normal separation of all three components of the developing outflow tract, but also to produce normal formation of the arterial valvar leaflets. Perturbing the contributions from the neural crest not only can produce abnormal arterial valves with two leaflets, but also double outlet right ventricle.Reference Phillips, Mahendran, Singh, Anderson, Chaudhry and Henderson ¹⁰

I would suggest, therefore, that the contribution from our colleagues in ParisReference Perdreau, Houyel and Baruteau ¹ provides a timely reminder that we need constantly to re-evaluate our descriptions of the normal and abnormal heart. As they have suggested, it now is far more sensible to describe malformations of the outflow tracts, rather than “conotruncal lesions”. This makes it possible to analyse malformations involving the proximal, intermediate, and distal parts of the developing outflow tract, and to relate these lesions to abnormalities in the ventricular outlets, the arterial roots, and the intrapericardial arterial trunks, respectively. If approached in this fashion, it should also prove possible to improve understanding between those investigating clinical aspects of cardiac malformations, and those who increasingly search for the genetic and molecular pathways which underscore their morphogenesis.