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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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