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 ‘functionally single ventricle’ is
preferred rather than ‘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
(>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
mm2/m2 [23]. In our patient
series, the mean pulmonary artery (Nakata) index was 293 ± 72
mm2/m2 (range 171 to 456
mm2/m2). 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
mm2/m2 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 SaO2 was lower in fenestrated
patients, the late postoperative SaO2 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‘ten commandments’ of Choussat [7] or the ‘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.