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and 92%. Hemodynamic re-evaluation at 1 year after Fontan
procedure showed a good surgical result without stenoses of
the conduit, the aortic arch, or the LPA. Significant in-stent
intimal proliferation was excluded, but left-sided pulmonary
perfusion was dramatically impaired (Fig. 1). Angiography
demonstrated, in particular, nearly no capillary perfusion
and lost flow to the left upper lobe (Fig. 3). LPVstenosis was
excluded by selective angiography and magnetic resonance
imaging (MRI). Phase-velocity (PV)-MRI confirmed the
significant perfusion mismatch taking the smaller left lung
into particular consideration (Fig. 2). Selective pulmonary
vein blood gas probes demonstrated a significant difference
in oxygen power (Table 1).
The patient remained on oral anticoagulation. Mont-
elukast was added to optimize bronchial and pulmonary
function, especially in the left lung. Five months later (after
we finished addressing administrative, ethical, and organi-
zational issues), oral phosphodiesterase V-inhibitor silde-
nafil was started at the recommended dose of 20 mg orally
three times daily (3.5 mg/kg/d) with the intention to
improve lung perfusion by decreasing PVR by way of the
nitric oxide (NO)-dependent pathway. PV-MRI 3 months
later demonstrated a significant improvement in left pul-
monary perfusion. This could be confirmed by cardiac
catheterization with recruitment of the capillary vascular
bed (Fig. 4). The transpulmonary pressure gradient
decreased, and left-ventricular filling pressure increased.
The patients clinical state improved from Ross classifica-
tion II to I. Treadmill exercise testing on sildenafil treatment
verified VO2 max of 32.5 ml/min/kg. Unfortunately, we
were not able to perform treadmill exercise testing before
treatment. Table 1 lists the patients hemodynamic data,
lung function, and clinical parameters before and on silde-
nafil medication.
Discussion
Despite a good surgical and interventional result, pul-
monary perfusion can be significantly impaired in the
nonpulsatile Fontan circulation. In our patient, the post-operative anatomy was favorable to direct the blood pref-
erentially to the smaller left lung. However, there was no
efficient blood flow to the left side despite effective stent
therapy of LPA branch stenosis and optimized airway
therapy (Fig. 1). This problem was successfully overcome
by administration of oral sildenafil, which restored left-
sided pulmonary perfusion with significant and sustained
clinical benefit (Fig. 4).
The problem of acquired LPA branch stenosis or atresia
after aortic arch reconstructions in patients with Fontan
circulation has been reported by Zachary et al. [11]. In a
small cohort of seven patients, they were able to show that
Fontan procedures can be performed quite satisfactory in a
functionally single-lung situation but that there is a sig-
nificant difference in systemic arterial saturations after
surgery compared with patients having continuous pul-
monary arteries. However, there are no data about the long-
term course, and it is difficult to imagine that single-lung
physiology would have no adverse effect in Fontan
patients. Thus, recovery of every single pulmonary vessel
is mandatory.
Fig. 1 High-flow SVC-angiography (9 ml/s, 25 frames/s) with patent
LPA stents but no flow to the left lung despite a favourable anatomy
Fig. 2 PV-velocity MRI demonstrates significantly decreased flow to
the small left lung. Signal extinction in the proximal left pulmonaryartery is due to the implanted stents
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Still, there is a significant lack of data of pulmonary
vascular alterations in patients with a nonpulsatile per-
fusion. Initially the lungs of those patients, and espe-
cially their vessels, should be assumed to be healthy.
However, in case of decreased ventilation and persistent
alveolar hypoxemia, the Euler-Liljestrand reflex will lead
to pulmonary vasoconstriction. Whether or not this
relates to the NO-dependent pathway remains uncertain.
However, in our case, this mechanism could have con-
tributed to initiating the increased left-sided PVR,
although the initial problem of the left mainstem bron-
chus compression did not persist as an ongoing clinical
problem. In children after bidirectional cavopulmonary
anastomosis, Kurotobi et al. [5] demonstrated attenuation
of the endothelium-dependent vasorelaxation to be pro-
nounced in the patient with nonpulsatile perfusion com-
pared with those having an additional flow source.
Khambadkone et al. [4] demonstrated that basal PVR canbe decreased by inhaled nitric oxide (iNO) even late
after Fontan procedures. The effect of sildenafil seems to
be quite analogous to iNO because sildenafil increases
endothelial levels of cyclic guanosine monophosphate in
the pulmonary vasculature, resulting in relaxation. The
beneficial effect of single-dose sildenafil on exercise
capacity after Fontan procedure was shown by Giardini
et al. [2]. There are case reports about sildenafil therapy
with positive effect in Fontan circulation, especially in
cases of a failing circulation [3, 8, 9].
In our case, increased PVR occurred only in the left
lung. Virtually, the complete minute volume passesthrough the right side (minus the right-to-left shunt by way
of the fenestration and the coronary venous drainage).
Therefore, in view of the low pressure (12 mmHg
[Table 1]), the right-sided PVR must be less than normal.
This compares favourably with the situation of a simple
atrial septal defect with significant recirculation at normal
PA pressures, thus resulting in decreased PVR. Pulsatile
flow is necessary for recruitment of pulmonary capillaries
[7]. Therefore, absence of pulsatile flow in Fontan patients
is suspected to be another reason for increased PVR
because of lower endogenous nitric oxide release and
subsequent endothelial dysfunction [10]. Levy et al. [6]
compared clinical outcomes with results of pulmonary
biopsy specimens obtained during Fontan completion.
Patients with subsequent failing circulation had musculated
distal arterioles, and nitric oxide synthase expression was
significantly increased; however, endothelin-1 expression
remained low in both groups. Therefore, we favoured
treating the NO-dependent pathway in the presence of low
pulmonary pressures.
The quantification and side-dependent measurement of
pulmonary flow, with subsequent calculation of PVR, in
children is difficult and technically demanding. Phase-
velocity MRI seems to be an excellent method for ana-
tomical and functional evaluation and, especially, quanti-
fication of pulmonary blood flow in Fontan patients [1].
Compared with lung-perfusion scintigraphy, this method is
able to quantify lung perfusion with high accuracy, even
in patients with complex single-ventricle physiology and
nonpulsatile lung perfusion. However, conventional selec-
tive angiography seems to be superior to differentiate
between improved global and specific capillary perfusion
(Figs. 3, 4).
Table 1 Hemodynamics and pulmonary function
Before
sildenafil
With sildenafil
(3.5 mg/kg/d)
Oxygen saturation (%) 91 92
NT-ProBNP (ng/l) 144 90
Comedication Carvedilola Carvedilola
Montelukastb
Montelukastb
Warfarinc Warfarinc
Hemodynamic parameters
Pressures (mmHg)
LA 5 9
RPA 12 12
LPA (distal from the stent) 13 14
IVC 14 14
Conduit 12 14
SVC 12 15
LV 105/07 90/011
Descending aorta 115/62 107/51
LA to conduit (pullback)d 5 5
Oxygen content (room air)
RPV (mmHg) 76 75
PaO2 (%) 94 94
Left LPV (mmHg) 56 46e
PaO2 (%) 85 75
Left UPV (mmHg) 51 51
PaO2 (%) 84 80
Pulmonary function (%)
FVC 70 78
FEF 1 80 84
MEF 75 70 95
MEF 50 86 86
MEF 25 101 96
UPV upper pulmonary veina At 0.35 mg/kg/db At 0.23 mg/kg/dc INR 2 to 3d Mean pressure gradiente Decreased PaO2 was probably caused by intrapulmonic shunting
(see small vessel in left lateral basal lung [Fig. 3])
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Conclusion
Our case demonstrates that sildenafil is able to re-establish
lost unilateral pulmonary perfusion in patients with non-
pulsatile Fontan circulation. This effect on the capillary
level can only be visualised with sufficient accuracy by
conventional angiography, whereas PV-MRI better quan-
tifies the side differences. Sildenafil caused significant
hemodynamic and clinical improvement and was well
tolerated without adverse effects. It seems to be a safe and
worthwhile therapeutic option in cases of acquired loss of
alveolo-capillary bed.
Acknowledgments The surgical procedures were performed by
V. H. at the Universitares Herzzentrum Hamburg, Hamburg, Germany
(stages I and II) and at the Deutsches Kinderherzzentrum, Asclepios
Klinik Sankt Augustin GmbH, Sankt Augustin, Germany (stage III).
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