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\begin{document}

\title{Beyond transplant: Roles of atrial septostomy and Potts shunt in
pediatric pulmonary hypertension}



\author[1]{Ronald Grady }%
\affil[1]{Washington University in Saint Louis School of Medicine}%


\vspace{-1em}



  
  \date{June 13, 2024}


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\begin{abstract}
Despite significant successes in treating children with pulmonary
hypertension, many still die from their disease. Death most often
results from right ventricular failure. Bilateral lung transplantation
has historically been the ultimate palliation for children who develop
heart failure despite maximal medical therapy. Creating an atrial level
shunt has been advocated as a pre-transplant intervention to help reduce
symptoms and perhaps serve as a bridge to transplant. More recently, the
utilization of a pulmonary-to-systemic anastomosis, i.e., Potts shunt,
has demonstrated efficacy in ameliorating symptoms in children with
severe, progressive disease. This improvement is often coincident with a
reduction in expensive and onerous pulmonary hypertension specific
medications. Improvement has been sustained over years in some children,
delaying the need for transplant consideration. Research is ongoing to
determine more specific risk/benefits of using the Potts shunt in
children with pulmonary hypertension both in the short term and long.%
\end{abstract}%



\sloppy


\textbf{Keywords}

pediatric pulmonary hypertension, atrial septostomy, Potts shunt

\textbf{Running Head}

Potts shunt and pediatric pulmonary hypertension



\textbf{Introduction}

The treatment of children with pulmonary hypertension (PH) has evolved
dramatically over the last 30 years. Early data demonstrated a median
survival of less than one year whereas current estimates now predict
5-year survival rates of at least 80\%. \textsuperscript{1,2,3} This
improvement likely reflects the development of PH-specific drugs and an
increased awareness and understanding of PH pathology along with the
development of specialized centers and personnel to treat it.
Nonetheless, despite these advances, children still die from their
disease. Children with severe PH who fail aggressive medical management
have limited options. Historically, lung transplantation has been the
palliative procedure most often considered in these critically
compromised children. However, survival with pediatric lung
transplantation remains relatively limited with current median survival
of \textasciitilde{}7 years in children transplanted for idiopathic PH
and even lower survival for children with non-idiopathic PH, a median of
\textasciitilde{}3 years.\textsuperscript{4,5} In addition, lung
transplantation involves expensive, highly technical and specialized
care that only a relatively small number of centers around the world can
afford to offer. Consequently, care providers have looked for other ways
in which to treat these medically refractory children. Ultimately, most
children with severe PH die because of right ventricular failure. Thus,
a number of interventions have developed over the years as a means to
ameliorate right ventricular dysfunction short of transplantation.
Physiologically these procedures fall into two categories: 1) creating a
pre-tricuspid valve shunt, essentially making an atrial septal defect,
or 2) creating a post-tricuspid valve shunt, typically a
pulmonary-to-systemic anastomosis at the level of the great vessels,
e.g., a Potts shunt. We will discuss these options in more detail. Other
interventions for supporting the failing right ventricle such as ECMO,
paracorporeal lung assist devices or right ventricular assist devices
are therapies that are utilized almost exclusively in the intensive care
setting and will not be covered in this article.

\textbf{Atrial Septostomy and Pulmonary Hypertension}

Several observations in the 1980's suggested that adult patients with
severe, symptomatic PH who also had a patent foramen ovale had a
survival advantage over those who did not.\textsuperscript{6,7}

Improvement in those with atrial defects was postulated to result from
the shunt ``decompressing'' the failing right ventricle, allowing for
right to left atrial flow, thereby improving left ventricular preload
and thus augmenting cardiac output and oxygen delivery (albeit with
overall reduced systemic oxygen saturations). A number of relatively
small case series followed, primarily in adults, demonstrating that in
the select patient creating an atrial shunt via atrial septostomy (AS)
could improve symptoms and possibly serve as a bridge to
transplant.\textsuperscript{8,9} Whether AS improves survival however is
less clear due to the lack of control cases. Nonetheless, several
studies have argued that when compared to historical controls or
calculated survival, patients who underwent AS fared
better.\textsuperscript{9} Studies that look specifically at AS in
children are few. One retrospective study reviewed 20 children with a
mean age of 8.4 years who underwent AS.\textsuperscript{10} All were
World Health organization functional class (WHO-FC) III or IV, 13
suffered from recurrent syncope. There were no procedural deaths.
Post-procedure, functional class improved significantly and syncope was
abolished in 12 of the 13 children. With a mean follow-up of 2.1 years,
clinical improvement was maintained in 18 of the 20 children. Notably
however, despite clinical improvement post-AS, 9 of the children (45\%)
required the addition of intravenous epoprostenol to their medical
regimen. Overall, enough evidence exists to recommend including AS as
part of the standard, pediatric PH treatment algorithm for symptomatic
children on maximal medical therapy.\textsuperscript{11} The importance
of patient selection and technique in regards to a successful outcome
dictate that this relatively high risk procedure (mortality over 20\% in
some adult series) should be performed in centers with significant
experience.\textsuperscript{9}

The ability of a pre-tricuspid (atrial) shunt to provide symptomatic
relief in a child with PH depends upon having right atrial pressures
high enough to force blood to flow from the right atrium to the left.
Assuming a competent tricuspid valve, right atrial pressure is directly
reflective of right ventricular end diastolic pressure (RVEDP).
Consequently, for an atrial shunt to benefit a PH patient, the RVEDP
must be abnormally elevated to generate right-to-left atrial flow. This
elevation of RVEDP can happen acutely, as with exercise, or as the
result of progressive right ventricular failure with decreasing systolic
function and concomitantly rising RVEDP. Thus, a child with PH who
improves from an AS is often one whose right ventricular failure is
relatively advanced, perhaps suggesting why children who have had an AS
may still require additional PH medications and where survival outcomes
may not be obviously improved.\textsuperscript{10,12,13} This relatively
``end stage'' benefit of an AS contrasts with the potential advantage
that a post-tricuspid shunt has to intervene much earlier in a child's
disease course.

\textbf{Potts Shunt and Pulmonary Hypertension}

Typically, creation of a post-tricuspid shunt involves an anastomosis
between the descending aorta and the left pulmonary artery, a surgical
technique first described in 1946 by Dr. Willis
Potts.\textsuperscript{14} The original goal of his eponymous shunt was
to provide pulmonary blood flow to a child with tetralogy of Fallot at a
time when cardiopulmonary bypass was not available. The procedure fell
out of favor once primary repair became standard. However, in 2004, a
group from H\selectlanguage{ngerman}ôpital Necker-Enfants Malades in Paris, France resurrected
the Potts shunt to treat two boys suffering from severe, suprasystemic
right ventricular systolic pressures.\textsuperscript{15} Their
insightful theory postulated that by creating an unrestrictive
pulmonary-to-systemic shunt, the afterload on the right ventricle would
be reduced to systemic levels and thereby recapitulate the
pathophysiology seen in patients with Eisenmenger's syndrome. By doing
so, the researchers hoped to confer upon these children the relatively
superior life expectancy purported for patients with Eisenmenger's
syndrome.\textsuperscript{16,17} One immediate consequence of the shunt
would be to send deoxygenated blood to the lower half of the body, while
preserving the highest oxygenated blood for the upper half and the brain
in particular. This contrasts with an AS that leads to global
deoxygenation. The two children experienced significant improvement both
clinically and hemodynamically with follow-up at 6 and 18 months
respectively.

This initial success led the way for their publication of 24 consecutive
children with PH treated with a Potts shunt in
2012.\textsuperscript{18}In this series, children's ages ranged from 1.5
to 17 years with the majority classified as severely compromised with
WHO-FC IV. Nineteen of the children had a traditional shunt via a left
thoracotomy and direct anastomosis of the pulmonary artery and the
aorta. Five had transcatheter shunts through the stenting of a
restrictive patent ductus arteriosus (PDA). There were 3 procedural
deaths (12.5\%). Children that went home had a median follow-up of 2.1
years with 7 children having over 8 years follow-up post-procedure.
There was rapid clinical and hemodynamic improvement with better WHO-FC
(from a median FC IV to II), longer 6 minute walk distances, lower brain
natriuretic peptide (BNP) levels and improved echocardiographic
findings. Perhaps most remarkable, these improvements occurred while
weaning PH medications. Indeed, 6 of the children that were on
intravenous epoprostenol pre-operatively were weaned completely off
post-shunt. This contrasts with studies of patients undergoing AS for
palliation where medical regiments often increased
post-procedure.\textsuperscript{10,13} Overall, this series demonstrated
that a child with severe PH, WHO-FC IV on intravenous prostacyclin
therapy, could experience a sustained, prostacyclin-free, improved
quality of life by means of a Potts shunt.

In 2016, a group from Washington University in St Louis, USA published a
series of five consecutive children who had undergone a surgical Potts
shunt for severe PH.\textsuperscript{19} Their findings mirrored that of
the Parisian group, demonstrating in 4 of the children, with less
follow-up (mean \textasciitilde{}10 months), an improvement in
functional class and BNP levels. Since that publication, the St Louis
group has performed a total of 23 Potts shunts in children with a mean
age of 10.3 years (range 0.3-20 years) with diagnoses including
idiopathic PH, heritable PH, PH associated with congenital heart disease
and PH associated with lung disease (personal observation). Twenty had
surgical shunts, either through 1) direct anastomosis, 2) the use of a
short inter-arterial graft or 3) with a valved conduit placed via a
sternotomy. Three children had catheter-based interventions, two with
PDA stenting and one with reopening a previously device-closed duct.
Four of the children died (17\%) within 30 days of the procedure. Three
of these early mortalities were children who presented in extremis,
requiring veno-arterial ECMO prior to their shunt. The fourth child died
from progressive hypoxia due to interstitial lung disease. Nineteen of
the children were discharged home with a mean follow-up of 2.5 years
(range 0.5-6 years). Seventeen of these children showed improvement
clinically with lower WHO-FC scores, lower BNP levels and a reduction in
overall PH medications. There were four late deaths and two lung
transplants post-shunt. Reasons for death or transplant included
worsening right ventricular failure, acute infection and one due to
accidental tracheostomy tube dislodgement.

The data from Paris and St Louis demonstrate, with a combined mean
follow-up of 2-3 years, that a Potts shunt can provide symptomatic
improvement in children with severe PH. The question of longer-term
benefits, however, remains open. The original idea behind utilizing a
Potts shunt was to ``convert'' a child to Eisenmenger-like physiology
and possibly confer the purported survival benefits seen with
Eisenmenger patients. This conferral of benefit assumes that a child
with PH due to an etiology distinct from Eisenmenger's syndrome would
respond similarly to right ventricular decompression. In adult series,
median survival with Eisenmenger syndrome has been estimated as long as
40-60 years, far better than that reported in children with
PH.\textsuperscript{2,3,16,17} The survival rate for children with
Eisenmenger's syndrome, however, may not be as robust as seen in adults,
with one estimate of 77\% survival at four
years.\textsuperscript{20}Nonetheless, even this reduced survival
projection would still compare favorably to that of children who
typically present for Potts shunt consideration, specifically, those who
are WHO FC IV despite PH specific therapy. These compromised children
have a purported median survival of less than two
years.\textsuperscript{21}

To address survival benefits and other aspects regarding the use of a
Potts shunt in treating children with PH, an international registry with
at least fourteen centers has begun to compile data. Even without
registry results, however, there are relevant observations and
discussions that can be made regarding the Potts shunt and PH. From the
St. Louis experience, three children were sick enough prior to their
shunt procedure to require veno-arterial ECMO (personal observation).
All three had surgical shunts and all three died in house within 30 days
of their procedure. These results would suggest that in the severely
decompensated child, a Potts shunt might not be an effective option. In
fact, if these three children were excluded, acute mortality in the St
Louis series would drop from 17\% to less than 5\%. Thus, as with most
procedures, increased experience in patient selection can lead to
improved surgical outcomes. Certainly, if a child's anatomy allows,
dilating and stenting a restrictive PDA would be the route of choice for
creating a shunt, avoiding the potential morbidity from surgery.
Unfortunately, this option is seldom available. Several centers have
reported on creating a transcatheter shunt through direct puncture from
the aorta to the pulmonary artery with subsequent placement of a covered
stent.\textsuperscript{22,23} Between the two series, a total of ten
patients underwent this transcatheter procedure with four deaths, an
early mortality more than double of that seen in the St Louis and Paris
experience. This relatively high risk may preclude the transcatheter
Potts shunt from gathering widespread acceptance.

Not all children with severe PH will benefit from a Potts shunt. In
theory, because the shunt is an unrestrictive communication between the
pulmonary and systemic circulations, it will only be effective in
reducing right ventricular afterload in those whose right ventricular
systolic pressures are higher than the left, i.e., suprasystemic.
Documenting suprasystemic right ventricular pressures can be done with
either echocardiography or cardiac catheterization. Relying on right
ventricular ejection fraction alone, however, is not sufficient. In the
St Louis series, one child had a calculated right ventricular ejection
fraction by MRI of 16\% yet the echocardiogram still demonstrated
suprasystemic pressures. Post-procedure this child did well clinically
(personal observation). While a Potts shunt can successfully lower
suprasystemic right ventricular pressures, subsequent pressures will
still remain at abnormally high systemic levels. Consequently, a shunt
placed in a child whose right ventricle has lost the ability to generate
systemic to suprasystemic pressures may prove ineffectual. As a case in
point, one child, early on in the St Louis series, was diagnosed
initially with suprasystemic right ventricular
pressures.\textsuperscript{19} At the time of his shunt however,
echocardiograms demonstrated at most systemic right-sided pressures. The
child failed to improve post-procedure and eventually died three months
later from progressive right ventricular failure. Thus, intervening with
a Potts shunt should occur before the onset of frank right ventricular
failure, i.e., falling, sub-systemic, right ventricular systolic
pressures with rising RVEDP.

In theory, a post-tricuspid shunt like a Potts has the potential to
intercede relatively early in a child's disease course, while systolic
function is still preserved at suprasystemic levels and diastolic
pressures are comparatively low. This contrasts with an AS which relies
upon an elevated RVEDP to be effective, a situation more typical of
end-stage disease. This potential advantage of a Potts shunt over AS,
leads to the interesting question as to how early in a child's disease
course does one consider a shunt. Current recommendations suggest
considering a Potts shunt in a child with severe, symptomatic disease
who has failed aggressive medical therapy, including prostacyclin
infusion.\textsuperscript{11} However, does waiting for such a child to
develop symptoms reduce a shunts potential benefits and increase its
risks? Those answers are currently unclear. What is clear, however, is
that managing a 24-hour prostacyclin infusion places a substantial
burden upon a child and family and that a Potts shunt offers the hope of
easing that onus. Thus, perhaps intervention should be considered in a
child with severe PH who is still WHO FC I-II rather than III-IV. A
technical development that might provide impetus for employing a Potts
shunt earlier in a child's course is the use of a valved conduit to
create the inter-arterial anastomosis. A shunt that allows for only
right-to-left flow might benefit the child who at rest has systemic to
even sub-systemic right ventricular pressures yet with exertion develops
suprasystemic pressures with resulting symptoms. A recently published
series demonstrates the feasibility of such an
approach.\textsuperscript{24} Managing the inevitable development of
valve incompetency and a conduit's limitations in a growing child would
need to be considered.

For children with severe, progressive, medically recalcitrant PH,
bilateral lung transplantation remains the ultimate palliative option.
Whether a Potts shunt can provide a similar survival rate as lung
transplantation requires more data. A more immediate question, however,
is whether having a Potts shunt precludes further consideration for lung
transplantation. There is one reported case from the Paris series of a
child who had a Potts shunt and subsequently underwent successful lung
transplantation.\textsuperscript{25} This child initially did well
post-shunt with clinical improvement and weaning from her intravenous
epoprostenol. However, six years after her shunt, she developed severe,
persistent hemoptysis and was listed for transplant. On the day of her
transplant, her shunt was closed with a covered stent prior to her
operation. From the St Louis experience, three children post-shunt came
to transplant, two from progressive RV failure and one for hemoptysis
(personal observation). At the time of transplant, two were on
relatively high doses of IV prostacyclins and one was on veno-venous
ECMO. All three transplants were marked by severe bleeding which
resulted in two of the children dying post-operatively. The one survivor
recovered fully. Reasons for the profound bleeding are likely multifold
and include the known risk that prior thoracotomies have on chest wall
neo-vascularization and lung adhesions, failure to adequately control
the shunt at the time of transplant, and clotting derangements due to
medications such as prostacyclins. One technical modification that might
reduce these complications is to place a shunt through a sternotomy.
This approach could potentially reduce lung adhesions, provide better
control of the shunt at the time of transplant, and eliminate the need
for any additional peri-operative
procedures.\textsuperscript{24}Overall, while having a Potts shunt does
not prevent future consideration of lung transplantation, it does appear
to increase the risk and technical challenge of the operation. Lung
transplantation in of itself is a complex procedure. Consequently,
performing one on a child who has had a Potts shunt is not something
every transplant center is willing to consider. Therefore, before
proceeding with a Potts shunt, frank discussions with families about
possible future limitations and risks would obviously be important in
helping them make informed decisions.

\textbf{Conflict of Interest}

The author declares no conflict of interest.

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