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\begin{document}

\title{Recognising the remnants of the left venous valve}



\author[1]{Robert Anderson}%
\author[2]{Diane E. Spicer}%
\affil[1]{Newcastle University}%
\affil[2]{Johns Hopkins All Children's Hospital}%


\vspace{-1em}



  
  \date{May 17, 2024}


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This is an invited commentary. I did not think abstracts were required
for commentaries.%
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\emph{Recognising the remnants of the left venous valve}

Diane E. Spicer\textsuperscript{1} and Robert H.
Anderson\textsuperscript{2}

\textsuperscript{1}Heart Institute, Johns Hopkins All Children's
Hospital, St. Petersburg, FL, USA

\textsuperscript{2}Cardiovascular Research Centre, Biosciences
Institute, Newcastle University, Newcastle-upon-Tyne, UK

Short title: Left venous valve

Key words: Eustachian valve; Thebesian Valve; Systemic venous sinus;
Development

Address for communications:

Professor Robert H. Anderson

60 Earlsfield Road

London SW18 3DN

United Kingdom

sejjran@ucl.ac.uk

In an interesting brief report in this issue of the Journal, Feng and
his colleagues describe their experience with a valve related to the
orifice of the superior caval vein. They point out that, although
remnants of the valves of the embryonic venous sinus are well recognised
to persist in postnatal life as the valves of the inferior caval vein
and the coronary sinus, it is rare to find such valvar remnants related
to the orifice of the superior caval vein.\textsuperscript{1} As they
correctly explain, the remnants related to the inferior caval vein and
the coronary sinus are parts of a complete valvar complex. When first
formed, they mark the boundary, during embryonic development, between
the systemic venous sinus and the right atrium. In support of this
statement, they make reference to a recent study conducted by Hikspoors
and colleagues.\textsuperscript{2} This work provides a pictorial
account of the anatomical changes taking place during embryonic
development of the human heart. The beauty of this report, in which one
of us (RHA) was privileged to take part, is that the three-dimensional
datasets used by the investigators have now been made available as
interactive portable document format files.\textsuperscript{2} These
files can be interrogated and reconstructed by the interested reader. By
selecting the appropriate segmented components of the developing heart,
it is possible to appreciate how, at the early stages of development,
the systemic venous tributaries are bilaterally symmetrical, with
tributaries from the umbilical, vitelline, and cardinal systems draining
into the right and left sinus horns (Figure 1A). At this initial stage,
furthermore, each of the sinus horns is in direct continuity with the
atrial component of the developing primary heart tube. This process of
development is described as stage 12 within the system initially
proposed by the Carnegie Institute, where the serial sectioned human
embryos from which the reconstructions were made are still archived.
These processes take place during the fifth week of development. By the
next stage of development, or Carnegie stage 13, a remarkable change has
occurred. The systemic venous tributaries have remodelled in such a way
that the left sinus horn has become incorporated within the left
atrioventricular junction. As a result, the overall systemic venous
sinus then drains exclusively to the right side of the developing atrial
chambers (Figure 1B). It is this rightward shift of the systemic venous
tributaries that sets the scene for subsequent atrial septation. The
remodelling uses as a fulcrum the so-called dorsal mesocardium. This is
the stalk, which anchors the developing heart to the pharyngeal
mesenchyme. It is the connection provided through the dorsal mesocardium
that is used by the pulmonary vein as it canalises within the pharyngeal
mesenchyme, gaining its entry to the developing left
atrium.\textsuperscript{2} It is only subsequent to the rightward shift
of the systemic venous sinus that it becomes possible to recognise the
valves that guard its entrance to the remainder of the developing
morphologically right atrium. After this initial transfer, the left
sinus horn remains a significant channel, with the venous valves
themselves forming an obvious landmark when viewed from the cavity of
the right atrium (Figure 2).

This arrangement continues to term in animal species such as the mouse,
in which the left sinus horn persists as the left superior caval vein
(Figure 3). In normal human development, however, the left sinus horn
diminishes markedly in size. It persists only as the coronary sinus,
which then serves as the conduit for drainage of the larger part of the
venous return from the heart itself. In keeping with the diminution in
size of the left sinus horn, in the human heart there is comparable
diminution in prominence of the left venous valve. The right venous
valve also diminishes markedly in size, usually persisting as the
Eustachian and Thebesian valves, which guard the orifices of the
inferior caval vein and the coronary sinus. On occasion, nonetheless,
the right venous valve can persist to provide the substrate for division
of the morphologically right atrium, usually known as ``cor triatriatum
dexter''. This terminology is very confusing, since the lesion does not
produce a triatrial heart. The arrangement does no more than produce
more obvious division of the right atrial chamber.\textsuperscript{3} In
some instances, the persistent valve can become aneurysmal, and can
extend as a windsock through the tricuspid valve (Figure 4B). On other
instances, the valve can persist in intermediate form. It can then
produce the arrangement as described by the Chinese authors, and can
guard not only the orifice of the inferior caval vein and the coronary
sinus, but also the orifice of the superior caval vein (Figure 4A). As
can be seen in the example shown in Figure 4A, the valvar remnant is
continuous with a myocardial strip, which then extends into the cavity
of the pectinated right atrial appendage. This is the spurious septum,
or ``septum spurium''. It is the cranial commissure of the initially
complete venous valves. The caudal commissure becomes fibrous, and
persists as the tendon of Todaro.\textsuperscript{2}

But what of the left venous valve? As suggested by Feng and colleagues,
it, too, can persist as a discrete entity. It is questionable, however,
as to whether the valve, when not obvious, has been incorporated within
the atrial septum. The origin and components of the atrial septum itself
remain controversial. It is described as having primary and secondary
components. This much is true. The second component, however is not the
superior margin of the oval fossa, as is still frequently shown in
textbooks of embryology, anatomy, and cardiology. The superior rim of
the fossa is no more than an infolding of the walls of the right and
left atrial chambers.\textsuperscript{4} The true second atrial septum
is the inferior buttress of the oval fossa. This is formed by
muscularisation of the mesenchymal cap carried on the leading edge of
the primary septum itself, along with the vestibular spine. The latter
structure grows into the heart through the rightward boundary of the
dorsal mesocardium.\textsuperscript{2,4} When the left venous valve
persists, as it does in the murine heart (Figure 3B), then a space
exists between the valve and the floor of the oval fossa. This
intersepto-valvar space can still be recognised when the left venous
valve does persist in the human heart (Figure 5A). In fact, when
searched for carefully, the left venous valve is to be found more
frequently than currently believed. It can form a filigreed network
adherent to the margins of the oval fossa (Figure 5B), or as a fold,
which can co-exist with a similar fold directly beneath the orifice of
the superior caval vein (Figure 5C). As Feng and colleagues discuss,
these remnants of the venous valves related to either the superior caval
vein or the oval fossa, thus far, have rarely been encountered by
clinical cardiologists. As with so many things, however, when one is
aware of their potential existence, they are much more likely to be
recognised. Now that the structures have been brought to attention, it
is likely we will learn much more of their potential significance. Feng
and colleagues are to be congratulated on recognising the entities in
their patient for what they really are.\textsuperscript{1}

\emph{References cited}

\begin{enumerate}
\tightlist
\item
  Feng Q, Wang H, He Y. The supernumerary valve in the right atrium of
  the human heart: A rare case of ``the valve of superior caval vein''.
  J Card Surg 2022; in the press
\item
  Hikspoors JPJM, Kruepunga N, Mommen GMC, et al. A pictorial account of
  the human embryonic heart between 3.5 and 8 weeks of development.
  Commun Biol 2022; 5: 226
\item
  Trento A, Zuberbuhler JR, Anderson RH, et al. Divided right atrium
  (prominence of the Eustachian and Thebesian valves). J Thorac
  Cardiovasc Surg 1988; 96:457-463
\item
  Jensen~B,~Spicer~DE,~Sheppard~MN\emph{,} et al. Development of the
  atrial septum in relation to postnatal anatomy and interatrial
  communications. Heart\emph{~} 2017; 103:456-462.
\end{enumerate}

\emph{Legends to Figures}

\textbf{Figure 1.} The images are made by reconstructing the developing
systemic venous tributaries in developing human embryos, using the
interactive pdf files available from Reference \#2. The developing heart
is shown as viewed from behind. At Carnegie stage 12 (panel A), both
sinus horns are in direct continuity with the atrial component of the
developing heart tube (white arrows with red borders). One stage later,
as shown in panel B. the left sinus horn has become incorporated into
the developing left atrioventricular junction, losing its connection
with the left side of the developing atrial component (white star with
red borders). The systemic venous sinus then connects only with the
cavity of the developing right atrium. Note the location of the dorsal
mesocardium, which has served as the fulcrum for the remodelling.

\textbf{Figure 2.} The images are from a three-dimensional episcopic
dataset prepared from a human embryo at Carnegie stage 14. The venous
valves now mark the boundary between the systemic venous sinus and the
developing right atrium, as seen in the four chamber section shown in
Panel A. Panel B is a section showing how the systemic venous
tributaries now open within the confines of the venous valves. With
further development, the left sinus horn will become the coronary sinus.

\textbf{Figure 3.} The images are four-chamber sections through
three-dimensional episcopic datasets prepared from developing mouse
embryos. Panel A shows the arrangement at embryonic day 14, when
septation is complete, while panel B shows the situation at term. Both
venous valves persist.

\textbf{Figure 4.} The images show persistence of the right venous valve
in two human hearts. Panel A shows an example where the valve has
persisted as the Eustachian valve, guarding the mouth of the inferior
caval vein, as a prominent Thebesian valve guarding the mouth of the
coronary sinus, but also as a valve guarding the mouth of the superior
caval vein. The valve at the orifice of the superior caval vein is
reinforced by a muscular strap, which is the spurious septum. The arrow
shows how the strap passes in front of the entrance of the superior
caval vein to the right atrium. Panel B shows an example where the valve
has become aneurysmal, producing a windsock that has prolapsed through
the tricuspid valve.

\textbf{Figure 5.} The images show various human hearts with persistence
of the left venous valve (white arrow with red borders). Panel A shows a
four chamber cut across the oval fossa. In panel C, there is also
persistence of the venous valve guarding the mouth of the superior caval
vein (red arrow with white borders).\selectlanguage{english}
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