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\begin{document}

\title{Fontan Procedure in Patients with Preoperative Mean Pulmonary Artery
Pressure Over 15 mmHg}



\author[1]{Arda Ozyuksel}%
\author[2]{Baran Simsek}%
\author[2]{Omer Ozden}%
\author[2]{Sener Demiroluk}%
\author[2]{Murat Saygi}%
\author[2]{Mehmet Bilal}%
\affil[1]{Biruni University}%
\affil[2]{Medicana International Istanbul Hospital}%


\vspace{-1em}



  
  \date{May 04, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Several factors affect the long-term outcome of Fontan
procedure, but a high pulmonary artery pressure is still one of the most
important limitation for proceeding to a Fontan circulation. Herein, we
present our experience in Fontan patients with high preoperative
pulmonary artery pressures. Methods: A retrospective analysis was
performed in order to evaluate Fontan patients with a preoperative
pulmonary artery pressure \textgreater{} 15 mmHg between 2009 and 2020.
Sixteen patients were operated on with a mean preoperative pulmonary
artery pressure of 17.5 \selectlanguage{ngerman}± 2.1 mmHg. Results: Mean age at the time of
Fontan procedure was 7.8 ± 5.6 years. All of the patients had stage II
cavopulmonary anastomosis prior to Fontan completion, with a mean
interstage period of 4 ± 2.6 years. Fontan completion was achieved with
a polytetrafluorethylene (PTFE) tubular conduit, two of which were
intra-extracardiac. Fenestration was performed in 4 (25\%) cases.
Postoperative pulmonary artery pressures and arterial oxygen saturation
levels were 11.2 ± 2.8 mmHg and 97.8 ± 2, respectively. Mean duration of
pleural drainage was 3.9 ± 5.3 days. Any morbidity and mortality were
not encountered during a mean follow up period of 4.8 ± 7.7 years.
Conclusions: The mid-term results of stage III Fontan completion in
patients with pulmonary artery \textgreater{}15 mmHg are encouraging.
Pulmonary vascular resistance, not only pulmonary artery pressure may
help to identify high risk patients before Fontan completion.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\emph{\textbf{Text word count:} 4439}

\emph{\textbf{Number of tables:} 3}

\emph{\textbf{Number of figures:} 1}

\emph{Keywords:} \emph{congenital heart disease,} \emph{Fontan
Procedure, cavopulmonary anastomosis, pulmonary artery pressure, single
ventricle}

*\emph{Address for Correspondence:}

Arda \selectlanguage{ngerman}Özyüksel, MD, Assoc. Prof.

Medicana International Hospital Beylikduzu Cad. No: 3,

Beylikduzu, Istanbul, 34520, Turkey

e-mail:\emph{ozyukselarda@yahoo.com}

Tel: +90 212 8677500, Fax: +90 212 8677672

\textbf{ABSTRACT}

\textbf{Background} : Several factors affect the long-term outcome of
Fontan procedure, but a high pulmonary artery pressure is still one of
the most important limitation for proceeding to a Fontan circulation.
Herein, we present our experience in Fontan patients with high
preoperative pulmonary artery pressures.

\textbf{Methods} : A retrospective analysis was performed in order to
evaluate Fontan patients with a preoperative pulmonary artery pressure
\textgreater{} 15 mmHg between 2009 and 2020. Sixteen patients were
operated on with a mean preoperative pulmonary artery pressure of 17.5 ±
2.1 mmHg.

\textbf{Results:} Mean age at the time of Fontan procedure was 7.8 ± 5.6
years. All of the patients had stage II cavopulmonary anastomosis prior
to Fontan completion, with a mean interstage period of 4 ± 2.6 years.
Fontan completion was achieved with a
\emph{polytetrafluorethylene}(PTFE) tubular conduit, two of which were
intra-extracardiac. Fenestration was performed in 4 (25\%) cases.
Postoperative pulmonary artery pressures and arterial oxygen saturation
levels were 11.2 ± 2.8 mmHg and 97.8 ± 2, respectively. Mean duration of
pleural drainage was 3.9 ± 5.3 days. Any morbidity and mortality were
not encountered during a mean follow up period of 4.8 ± 7.7 years.

\textbf{Conclusions:} The mid-term results of stage III Fontan
completion in patients with pulmonary artery \textgreater{}15 mmHg are
encouraging. Pulmonary vascular resistance, not only pulmonary artery
pressure may help to identify high risk patients before Fontan
completion.

\textbf{INTRODUCTION}

Fontan Procedure (FP) had been a hope for many patients with congenital
heart diseases (CHD) when Dr. Francis Fontan (July
2\textsuperscript{nd}, 1929 -- January 14\textsuperscript{th}, 2018)
reported this technique for the first time in 1971 {[}1{]}. In this
original report, the FP was carried out in three patients with the
diagnosis of tricuspid atresia (TA). The right side of the heart was
bypassed with the combination of a classical cavopulmonary anastomosis
between the superior vena cavae and right pulmonary artery and
channeling the inferior venae cavae to left pulmonary artery with
interposing a homograft {[}2{]}. In his original paper, Dr. Fontan
emphasized the importance of well-developed pulmonary arteries with a
low pressure for the success of this operation.

In the following decades, the technique was further developed and
modified and on the other hand, the indications were hugely extended to
a variety of CHD with various morphologies. Probably the most important
evolutions in FP were the total cavopulmonary connection either with a
lateral tunnel or an extracardiac conduit and the idea of fenestration
{[}3-5{]}. In the current era of cardiac surgery, the potential
candidates for a Fontan procedure include a variety of CHD with one
well-developed ventricle or not {[}6{]}.

Early after describing FP, Dr. Fontan and his colleague Dr. Choussat
reported the criteria for an `ideal' Fontan candidate (table-1) {[}7{]}.
These guidelines, or namely \emph{`the 10 commandments'} were revised
and modified during the following decades, since all the criteria were
not necessarily portending excellent long-term survival when statistical
analysis were concerned {[}8,9{]}. Today, mean pulmonary artery pressure
(MPAP) and ventricular function are probably the most prevailing
criteria for selecting a patient before constituting a Fontan
circulation.

Herein, we aimed to present our experience in 16 patients with a MPAP
over 15 mmHg who underwent Fontan operation. We also discussed some
aspects of mandatory criteria for a satisfactory outcome after FP with
regard to the data reported in literature.

\textbf{MATERIALS and METHODS}

A total of 232 Fontan procedures performed in our cardiac surgery center
between 2009 and 2020 were retrospectively analyzed following the
approval of institutional review board. Sixteen patients who underwent a
Fontan procedure with a preoperative catheterization-based measurement
of MPAP over 15 mmHg were identified. Afterwards; preoperative,
intraoperative and postoperative records were reviewed.

Sixteen patients (9 males, 7 females) with a preoperative MPAP
\textgreater{}15 mmHg were operated by a single surgeon and FP was
performed. Mean age was 7.8 ± 5.6 years (range: 2 to 26 years) and body
weight was 22.5 ± 8.3 kg (range: 15 to 46 kg) at the time of FP. The
mean period between the Glenn and Fontan operations was 4 ± 6.6 years
(range: 1.5 to 10 years).The demographic and operative properties of the
patients are demonstrated in table-2.

\textbf{RESULTS}

Thirteen patients (81\%) had situs solitus and 3 (19\%) patients had
situs inversus. We encountered double inlet ventricles in 6 of the cases
(37\%). Three patients had tricuspid and two patients had mitral
atresia. In thirteen out of 16 patients (81\%), one of the ventricles
were hypoplastic, right ventricle in 7 and left ventricle in 6 cases. In
3 cases, both of the ventricles were developed and the indication for
Fontan palliation were congenitally corrected transposition of the great
arteries (c-TGA) (pt. no 5 and 9) and a criss-cross atrioventricular
(AV) connection in the setting of double outlet right ventricle (DORV)
and a large ventricular septal defect (VSD) (pt. no 6).

Stage-1 palliation was deemed necessary in 8 of the cases (50\%). These
interventions included balloon atrial septostomy or surgical atrial
septectomy in order to increase mixing at the atrial level, pulmonary
banding in order to control pulmonary arterial pressure and flow and
modified Blalock-Taussig shunt (MBTS). Patient no. 6 had a history of
supramitral membrane resection along with pulmonary artery banding and
atrial septectomy. All of the surgical atrial septectomy procedures were
performed as concomitant interventions, none of the patients were
operated on for surgical atrial septectomy alone. Five patients (31\%)
had a history of systemic to pulmonary shunt surgery as stage I
palliation (pt. no 4,5,8,13 and 14). In patient no.13, early
postoperative shunt occlusion was encountered and primary surgical
thrombectomy was performed. In all other cases, MBTS grafts were
primarily patent until surgical closure at the following stages.

Stage-2 palliation was performed in all cases which included superior
cavopulmonary anastomosis and concomitant procedures, which included
atrial septectomy, pulmonary banding, pulmonary artery patch
augmentation and atrioventricular valve repair. The bidirectional Glenn
procedure was bilateral in patients 10, 14 and 15. Prior shunts were
clipped or divided at stage II, except for two cases. In patient no.8,
MBTS was still functional as an additional pulmonary blood flow source
and in pt. no 5, there was an unintentional residual shunt flow at the
time of stage III. Both of these cases were operated on at other cardiac
surgery centers at stage II palliation and these shunts were closed at
stage III.

Stage III Fontan completion was achieved with
a\emph{polytetrafluorethylene} (PTFE) tubular conduit
(GORE-TEX\selectlanguage{english}\textsuperscript{?}, W.L. Gore and Associates Ltd., Livingston,
Scotland) at sizes between 16 mm and 22 mm. Extracardiac Fontan
procedure was performed in all cases, except for pt. no 11 and 14 where
an intra-extra cardiac conduit was interposed. Concomitant procedures at
stage III included DeVega tricuspid annuloplasty, pulmonary artery
reconstruction, atrial re-septectomy and shunt closure. Fenestration was
performed in 4 cases (25\%) (pt. no 1,4,11 and 12). At the time of stage
III, all of the patients underwent preoperative cardiac catheterization
under local anesthesia and sedation. In pt. no7, a major aortopulmonary
collateral artery was occluded via femoral route before stage III
completion. We did not encounter any inferior vena cava interruption and
azygos vein continuity. The mean pulmonary artery (Nakata) index was
calculated as 293 +- 72 mm\textsuperscript{2}/m\textsuperscript{2} (range
171 to 456 mm\textsuperscript{2}/m\textsuperscript{2}). Interstage
period, i.e. the time between stage II and stage III operations were 4 +-
2.6 years (range 1 to 10 years). The stages of Fontan circulation and
concomitant procedures are summarized in table-3.

The mean preoperative MPAP measured at the catheterization lab and at
the operation room were 17.5 +- 2.1 mmHg and 16.5 +- 1.8 mmHg,
respectively. The central venous pressure (measured via internal jugular
vein catheter) that was recorded at the initiation of Fontan completion
in the operation room represented the MPAP, since all the patients had a
prior cavopulmonary anastomosis. All of the patients had antegrade
pulmonary blood flow except for the patients no. 4 and 5 who had atresia
of the pulmonary valve. The antegrade pulmonary blood flow was
diminished either by native valvular or subvalvular pulmonary stenosis
and/or a pulmonary band placed at the time of bidirectional Glenn
procedure in 13 of the cases, except patient no. 10, who had a double
inlet left ventricle with restrictive VSD. The mean pulmonary arterial
gradient (except pt. no 4, 5 and 10) was 73.5 +- 10.2 mmHg (range 50 to
86 mmHg) at the time of Fontan operation. Postoperative MPAP and
arterial oxygen saturation levels were 11.2 +- 2.8 mmHg (range 4 to 15
mmHg) and 97.8 +- 2 (range 93 to 100), respectively. The preoperative and
postoperative MPAP values of the patients following the Fontan
completion are presented in figure-1.

\textbf{Surgical Technique}

Re-sternotomy was performed in all cases. Femoral cannulation and
initiation of cardiopulmonary bypass before sternal re-entrance was not
deemed mandatory in any of the cases. Following aortic and bicaval (or
tricaval in cases with a persistent superior venae cavae) cannulation
aorta was cross clamped except pt. no 12. Cold antegrade blood
cardioplegia was administered where intermittent doses were applied at
every 15 minutes. Pulmonary artery was divided above the level of
pulmonary valve, except for the cases with pulmonary atresia where there
was no antegrade pulmonary blood flow. Pulmonary cusps were excised or
squeezed between the double row matress suture lines closing the
pulmonary outflow of the ventricle. Inferior venae cavae (IVC) was
transected at the level of atrial entrance and a PTFE tubular conduit
was anastomosed to IVC with an end to end fashion. End to side
anastomosis was performed between the pulmonary artery and the conduit
and care was taken in order not to compress the pulmonary venous return
throughout the course of the conduit from IVC to pulmonary artery in the
pericardial cavity. In cases where an intra-extracardiac technique was
implemented, the anastomosis was performed within the atrium encircling
the ostium of the IVC. Then the conduit was passed from the atrium to
outside into the pericardial cavity. Total circulatory arrest was not
used in any case. When fenestration was needed, in cases with an
extracardiac technique, a side to side anastomosis was performed between
the conduit and the atrium. In intra-extracardiac Fontan cases, a punch
was used to make a fenestration and leave it inside the atrium.
Temporary inotropic agents were infused in pt. no 3,4 and 7 where
dobutamine was the first line choice. In patient no. 14, pulmonary
reconstruction was performed following transection of the ascending
aorta in order to provide better exposure of the pulmonary arteries.
Permanent pace maker was not necessary in any case. The mean
cardiopulmonary bypass and aortic cross clamp times were 69.7 +- 27.1 and
51.6 +- 25.3 minutes, respectively. All of the patients were
hemodynamically stable with the sternum closed when they leaved the
operating room. Any postoperative revision for bleeding or any other
reason was not encountered in the early postoperative period.

The mean duration of intubation and intensive care unit stay were 7.8 +-
3.5 hours and 2.3 +- 3.5 days, respectively. The chest drainage tubes
were in place until the daily drainage was less than 2cc/kg. Mean
duration of drainage was 3.9 +- 5.3 days. Oral warfarin, aspirin,
sildenafil citrate and bosentan were routinely administered in all of
the patients after FP. The target INR was 2 to 2.5. Steroids were
administered when the daily drainage exceeded 5cc/kg. Following removal
of the chest tubes, daily consecutive chest x-rays were obtained in
order to detect pleural effusion. Any chest tube re-insertion was not
needed for re-accumulation of the pleural fluid. We did not encounter
any phrenic nerve paralysis in this patient population. Mean duration of
discharge was recorded as 10 +- 1.8 days.

Mean follow up period was 4.8 +- 7.7 years (range: 1 to 11 years). All of
the patients are on lifelong Aspirin (5mgr/kg) therapy. Oral warfarin
and sildenafil citrate (3mgr/kg in 3 divided doses) are administered at
least for one year, and afterwards individual decision is given
primarily according to a presence of fenestration. Oral endothelin
receptor antagonist, bosentan is administered at least for one month.
All of the patients were discharged with diuretics and angiotensin
converting enzyme inhibitors in order to achieve a normal blood
pressure.

Early or mid-term Fontan failure and mortality was not encountered. In
pt. no 14, fenestration was closed via femoral access one year after the
FP. We have not encountered any case with significant arrhythmia,
plastic bronchitis or protein losing enteropathy in our patient
population. In cases with AV valve repair, trace to mild regurgitations
are encountered. All of the patients in our population are followed up
with ejection fractions above 50\% with NYHA class I-II symptoms at
annual outpatient visits.

\textbf{DISCUSSION}

Fontan circulation had been evolved to overcome situations in which two
distinct ventricular chambers are not readily available to pump blood
into pulmonary and systemic circulations in a parallel fashion. In fact,
in early 1940s, it was speculated that pulmonary vascular pressure was
lower than systemic venous pressure and this pressure gradient may be
sufficient to propel blood to the lungs without a power source (i.e.
right ventricle) at least in animal models {[}10{]}. Beginning from the
initial description of the FP in human in early 1970s, the surgical
evolution of the surgical procedures in single ventricle physiology may
be classified in 4 generations: i. First generation -- atriopulmonary
Fontan Kreutzer procedure; ii. Second generation -- lateral tunnel
Fontan procedure; iii. Third generation -- the extracardiac conduit
Fontan procedure; Fourth generation -- the intra/extracardiac conduit
with fenestration {[}11{]}. In addition to single ventricle situations,
in some cardiac malformations, the biventricular approach is avoided and
the patients are treated with construction of a Fontan pathway such as
inadequate ventricles (eg. hypoplastic left ventricle in Shone's
syndrome) or AV valves (eg. tricuspid stenosis with pulmonary
atresia/intact ventricular septum), c-TGA, unbalanced AV canal defect,
DORV with non-committed VSD or heterotaxy syndromes with complex
ventricular relationships {[}12{]}. For the purpose of clarifying the
nomenclature, the term \emph{`functionally single ventricle'} is
preferred rather than \emph{`single ventricle'} since some
abovementioned cardiac anomalies have well developed but non-septatable
ventricles {[}13{]}. In our current practice, we prefer to perform
intra-extracardiac FP in cases with unusual systemic venous and
pulmonary artery relationships as well as patients whom a fenestration
may be necessary. In our patient population, we operated on three
patients with well-developed two ventricles in order to construct a
Fontan circulation, two patients with c-TGA and one patient with DORV
and criss-cross AV connection.

Inherent to Fontan circulation, chronic elevation of systemic venous
pressure and absence of a power source for pumping blood to the
pulmonary vascular bed, low pulmonary artery pressure and vascular
resistance as well as an optimal systemic ventricular function are
essential ingredients of successful long-term results {[}14{]}.
Beginning from the traditional ten commandments, AV valves have been
repaired, subaortic and aortic arch obstructions have been relieved,
pulmonary vascular geometry has been optimized, encouraging results have
been reported in patients less than 4 years of age and arrhythmias have
been taken under control, therefore these 10 factors have been reduced
to two in mid 2000s: preoperatively impaired ventricular function and
elevated pulmonary artery pressure {[}7,15{]}. Moreover, the pulmonary
vascular impedance is stated to be the single most important factor
limiting cardiac output in some reports {[}16{]}. Interestingly, only
15-20\% of total pulmonary compliance is determined by the proximal
pulmonary arteries {[}17{]}.

At least five papers in English literature emphasize the elevated MPAP
(\textgreater{}15 mmHg) as an important predictor of long-term results
in Fontan patients {[}14,18-21{]}. On the other hand, in a recent study
of Tran and colleagues, elevated pulmonary artery pressure, not
pulmonary vascular resistance (PVR) is reported to be associated with
short-term morbidity, in patients with bidirectional cavopulmonary
connection {[}22{]}. In our preoperative evaluation, we did not
routinely perform pulmonary vascular resistance calculation. Another
parameter with regard to pulmonary artery architecture is emphasized by
Itatani and co-workers in which the lower limit for pulmonary artery
(Nakata) index is stated to be 110
mm\textsuperscript{2}/m\textsuperscript{2} {[}23{]}. In our patient
series, the mean pulmonary artery (Nakata) index was 293 +- 72
mm\textsuperscript{2}/m\textsuperscript{2} (range 171 to 456
mm\textsuperscript{2}/m\textsuperscript{2}). On the other hand, in the
original paper published by Fontan and colleagues, a McGoon ratio of 1.8
and a pulmonary artery index of 200
mm\textsuperscript{2}/m\textsuperscript{2} is defined as a necessary
criterion for the indication of a Fontan procedure {[}24{]}.

Another important concern in patients with Fontan physiology is chronic
pulsatile flow deprivation in the pulmonary circulation leading to an
impaired endothelial function and nitric oxide release, reduced vascular
recruitment and impaired lung growth, all leading to progressive
elevation in PVR {[}25,26{]}. Nevertheless, tachycardia in a normal
circulation may increase pulmonary blood flow by up to 35\% without
changing the diameter of impedance of the pulmonary vasculature and this
mechanism is lacking in Fontan patients {[}27,28{]}. At least three
exogenously administered pulmonary vasodilators are used to improve
exercise capacity and myocardial performance in Fontan patients:
iloprost (inhaled form of prostacyclin), sildenafil citrate
(phosphodiesterase-5 inhibitor) and bosentan (endothelin receptor
antagonist) {[}28{]}. In a recent meta-analysis, the oral forms of
pulmonary vasodilators significantly and safely improved the
hemodynamics of Fontan patients, reduced the NYHA functional class and
increased 6-minute walking distance {[}29{]}. In our clinical practice,
we use iloprost infusion at the early postoperative period in Fontan
patients when the central venous pressure rises over 10 mmHg, especially
during the period of extubation at doses between 0.5-2 ng/kg/min. We
administered oral sildenafil citrate and bosentan on the postoperative
first day routinely in this patient population. We did not have to
administer inhaled nitric oxide in our patients in the postoperative
period.

One of the important short-term morbidities following the operation of a
Fontan patient with high MPAP is prolonged pleural effusions. The
necessity for continued chest tube drainage often causes pain and
decreases ambulation of the patients. Prolonged pleural effusion is
defined as either effusion lasting longer than 14 days or an effusion
requiring an intervention for reaccumulated pleural fluid following the
removal of the chest tubes {[}30{]}. When this definition is considered,
we did not encounter any patients with prolonged pleural effusion in our
patient population, although elevated preoperative MPAP is reported to
be the single most determinant for this situation in some series
{[}30{]}. Mean duration of drainage was 3.9 +- 5.3 days in our patients.
We used the criterion of 2cc/kg/day drainage for chest tube removal as
recommended in literature {[}31{]}. We agree with the factors reported
by Arsdell and colleagues in order to minimize pleural drainage:
utilization of the extracardiac conduits, acceptable periods of aortic
cross clamping and cardiopulmonary bypass, modified ultrafiltration and
institution of inotropes and vasodilators when necessary for an optimal
intravascular volume and cardiac output and early postoperative
extubation {[}32{]}. In our patients, we deliberately used diuretics and
angiotensin receptor blockers in the postoperative period. Temporary
inotropic support was infused only in 3 of our patients. We think that
angiotensin receptor blockers are highly effective in order to control
afterload for an optimum cardiac output of the single ventricle as
stated in literature {[}33{]}. In patients whom the daily chest tube
drainage exceeded 5cc/kg, we administered steroids (first three doses
through intravenous route followed by oral tablets at a dose of 3 mgr/kg
methylprednisolone divided in three doses). The oral form of steroids
was gradually weaned and ceased after discharge; we did not administer
oral steroids more than one month although Rothman et al. reported a
weaning period over 3 -- 6 months {[}34{]}. At extreme cases of
uncontrolled pleural effusion, bleomycin or talc slurry may be used in
order to perform pleurodesis {[}35,36{]}.

Baffle fenestration, initially hypothesized for right-to-left
decompression and a smooth postoperative course is an important
modification in the history of Fontan physiology {[}5{]}. Bridges et al.
emphasized the benefits of fenestration including maintenance of optimal
cardiac output that may also reduce the incidence and duration of
pleural effusions. The authors assigned the patients to a fenestrated or
nonfenestrated groups. The fenestrated group had a higher risk profile
with regard to MPAP, pulmonary artery distortion and higher ventricular
filling pressures. Interestingly, the rate of Fontan failure was equal
in both groups but the fenestrated patients significantly had fewer days
with pleural effusion. Similar results were reported in a randomized
study published by Lemler and colleagues {[}37{]}. A recent
meta-analysis, a total of 4806 Fontan patients were evaluated in order
to analyze the effect of fenestration on Fontan procedure outcomes
{[}38{]}. The fenestrated group (a total of 2727 patients) had
significantly lower need for pleural drainage with a lower MPAP (-0.99
mmHg mean difference) and oxygen saturation (-3.07\% mean difference).
Importantly, there was no significant difference in stroke occurrence
between the fenestrated and nonfenestrated groups. Fenestration (a
right-to-left shunt) helps to increase preload, stroke volume and
cardiac output for the functioning ventricle at the expense of mild
cyanosis. Nevertheless, there's still no general consensus about routine
use of fenestration {[}38{]}. In our patient population, we did not
routinely perform fenestration during the Fontan procedure. The resting
room oxygen saturation levels were above 90\% in our fenestrated Fontan
patients. However, two essential factors should be outlined about this
procedure: the fenestration size and postoperative anticoagulation
protocol. We perform fenestration with a 4 or 4.5 mm punch on the
extracardiac conduit. A larger shunt is known to result in hypoxemia
induced acid base disturbance and increased pulmonary vascular
resistance with clinically overt cyanosis {[}39{]}. This vicious cycle
may result in decreased cardiac output. Secondly, although different
protocols are available avoiding chronic use of warfarin and
administering aspirin alone, we put all the patients on oral
anticoagulation and antiaggregant treatment following Fontan procedure
at least for one year {[}40,41{]}. At the end of the first year, we
decide to stop warfarin individually, however patients with fenestration
continue to use oral anticoagulants. We did not encounter any stroke or
conduit thrombosis in our patient group. Li et al. compared the
long-term results of fenestration on systemic oxygen saturation in a
meta-analysis including 1929 Fontan patients and reported that although
the early postoperative SaO\textsubscript{2} was lower in fenestrated
patients, the late postoperative SaO\textsubscript{2} levels did not
differ {[}42{]}. Therefore, some centers insist on routine fenestration
in all Fontan patients, but we still decide individually depending on
the perioperative MPAP value {[}43{]}.

Staged approach for achieving a successful Fontan circulation have been
advised in early 1980s {[}44{]}. Hopkins and associates recommended to
perform a bidirectional cavopulmonary anastomosis before a Fontan
completion. We adopted this approach in our clinic and all of the
patients in our patient population had a stage II Glenn anastomosis
before FP. In fact, this algorhythm has some important advantages.
Patients with a prior bidirectional cavopulmonary anastomosis tolerate
stage III FP better. Secondly, any additional intracardiac interventions
and/or optimization of a sufficient pulmonary vascular architecture
becomes possible. We performed pulmonary artery patch augmentation, AV
valve repair and atrial septectomy as concomitant procedures in stage
II. On the other hand, after the stage II palliation, systemic to
pulmonary artery shunts that are mandatorily interposed as stage I
interventions are closed. Early closure of a systemic to pulmonary
artery shunt is important, since the diastolic run off steals blood from
coronary circulation which may lead to deprived performance of the
future single ventricle. Moreover, bidirectional Glenn procedure is a
more effective way of pulmonary gas exchange and provides better
hemodynamic performance when compared to MBTS {[}45{]} . We uneventfully
performed bilateral bidirectional Glenn procedure in three patients as
stage II palliation, which is speculated to have a worse outcome
tendency in Fontan patients especially in association with pulmonary
artery bifurcation stenosis {[}46{]}.

Kreutzer and co-workers reviewed the reflections on five decades of the
Fontan Kreutzer procedure and grouped the factors that jeopardize the
late outcome into three categories: i. suboptimal surgical approach, ii.
ventricular dysfunction and iii. increases in pulmonary vascular
resistance {[}47{]}. On the other hand, Vigano and colleagues suggest
that in the modern era of congenital cardiac surgery, either
the\emph{`ten commandments'} of Choussat {[}7{]} or the \emph{`two
commandments'} of the Birmingham-UK group {[}14{]} are helpful for
identifying the `high risk' candidates for Fontan completion {[}48{]}.
They report that there is no actual difference in perioperative outcome
in a mean of 7 years follow up. Our results are consistent with their
findings.

Mean pulmonary artery pressure, transpulmonary gradient and PVR along
with ventricular function are still the most important parameters
addressing the long-term outcome of Fontan circulation {[}49{]}.
However, even the cardiac catheterization at increased altitudes may
present variability {[}49{]}. In fact, determination of the exact MPAP
value is not always reliable, since the pressure measurements may differ
when the patient is under local anesthesia and sedation at the
catheterization lab or under general anesthesia with neuromuscular
blockage in the operation room (17.5 +- 2.1 mmHg vs 16.5 +- 1.8 mmHg in
our patient population). Therefore, we recommend routine evaluation of
the PVR and transpulmonary pressure gradient in these patients. In
future, more real time monitorization tools for pulmonary artery
pressures may become available on routine basis and provide improved
management of pulmonary hemodynamics in Fontan patients {[}50{]}.
Obviously, the story of seeking for a perfect Fontan candidate and
research focusing on stem cells and optimal medical management
strategies will not end in the following decades {[}15{]}.

In our limited patient population, we think that Fontan procedure may be
performed with satisfactory mid-term results in patients with a
preoperative mean pulmonary artery pressure over 15 mmHg. These patients
should be carefully followed up after the operation for the well-known
complications in long term course of Fontan physiology.

\textbf{ACKNOWLEDGEMENTS}

None

\textbf{TABLE and FIGURE LEGENDS}

\textbf{Table -- 1:} Ten Commandments advised for an ideal Fontan
candidate (adopted from reference no.7).

\textbf{Table -- 2:} Summary of the patients who underwent Fontan
procedure.

\textbf{Table -- 3:} Operative details of the patients, concomitant
surgical procedures and summary of the stages of Fontan circulation.

\textbf{Figure -- 1:} The preoperative and postoperative mean pulmonary
artery values of the patients following the Fontan completion are
presented.

\textbf{AUTHOR CONTRIBUTIONS}

Arda Ozyuksel: Drafting the article, data analysis/interpretation, data
collection

Baran \selectlanguage{polish}Ş\selectlanguage{english}im\selectlanguage{polish}ş\selectlanguage{english}ek: Data analysis/interpretation, drafting the article, data
collection

\selectlanguage{ngerman}Ömer Özden: Data analysis/interpretation, data collection

\selectlanguage{polish}Ş\selectlanguage{english}ener Demiroluk: Concept/design, Critical revision of the article,
approval of the article

Murat Sayg\selectlanguage{polish}ı: \selectlanguage{english}Data analysis/interpretation, statistics, data collection

Mehmet Salih Bilal: Concept/design, Critical revision of the article,
approval of the article

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