since the first fontan procedure was introduced by fontan in 1971 , the surgical technique has evolved and the survival rate has shown dramatic improvement . recently ,
fontan surgery has been performed as an operation of the final stage for congenital heart disease with single ventricle physiology1 ) . in fontan circulation
therefore , the pulmonary vascular resistance ( pvr ) must be lower than the antegrade transpulmonary flow resistance2 ) .
thus , even a mild increase in the pvr may interfere with pulmonary circulation which in turn may result in decreased preload of ventricle , diminished cardiac output , and declined exercise tolerance3,4 ) .
loss of pulsatility of pulmonary flow , reduced growth of the pulmonary vasculature , micro and macro thromboembolism in pulmonary circulation and reduced ventricular function are underlying mechanisms that induce the high pvr in fontan circulation5,6,7 ) .
several studies8,9,10,11,12 ) reported the pulmonary vasodilating therapy had an effective influence on fontan patients so we want to determine whether inhaled iloprost as a pulmonary vasodilator might have a role in the clinical symptoms , hemodynamics and exercise capacity of fontan patients .
ethical approval for this study and permission for acquiring , analyzing and reporting of patient 's data were obtained in accordance with the guidelines of the institutional review board of gachon university gil medical center ( no .
an 18-year - old female with pulmonary atresia with intact ventricular septum status post fontan surgery at age of three years complained of aggravated dyspnea on exertion ( doe ) .
a physical examination showed regular heart beat without murmur and mild pitting edema on the pretibial area , liver and spleen were not palpable .
recently , she felt more difficult to climb the stairs due to shortness of breath .
the inhaled iloprost was administered at 60 microgram / day divided by six times for 12 weeks .
pre and post medication , laboratory test - including pro brain natriuretic peptide , cardiac catheterization , bicycle ergometer test , nyha class , and 6-minute walking test - were performed .
after 12 weeks , the patient 's systemic blood pressure and o2 saturation were increased .
six - minute walking distance was increased from 380 to 395 m and nyha class changed from iii to ii .
, the cardiac index and stroke volume were increased without significant change of pulmonary pressure and pvr .
the results are shown in table 1 . a 22-year - old male with double outlet right ventricle
after 12 weeks , the patient 's systemic blood pressure , o2 saturation , and nyha class were not changed significantly .
, the cardiac index and stroke volume were also increased without significant change of pulmonary pressure and pvr .
an 18-year - old female with pulmonary atresia with intact ventricular septum status post fontan surgery at age of three years complained of aggravated dyspnea on exertion ( doe ) .
a physical examination showed regular heart beat without murmur and mild pitting edema on the pretibial area , liver and spleen were not palpable .
recently , she felt more difficult to climb the stairs due to shortness of breath .
the inhaled iloprost was administered at 60 microgram / day divided by six times for 12 weeks .
pre and post medication , laboratory test - including pro brain natriuretic peptide , cardiac catheterization , bicycle ergometer test , nyha class , and 6-minute walking test - were performed .
after 12 weeks , the patient 's systemic blood pressure and o2 saturation were increased .
six - minute walking distance was increased from 380 to 395 m and nyha class changed from iii to ii .
, the cardiac index and stroke volume were increased without significant change of pulmonary pressure and pvr .
a 22-year - old male with double outlet right ventricle status post fontan surgery at age of five years complained of mild doe only .
after 12 weeks , the patient 's systemic blood pressure , o2 saturation , and nyha class were not changed significantly .
, the cardiac index and stroke volume were also increased without significant change of pulmonary pressure and pvr .
despite the increased survival rate of patients who has congenital heart disease with single ventricular physiology due to advanced surgical technique , the fontan surgery is still a palliative procedure .
development of the fontan failure state might occur gradually over time ; ventricular dysfunction , aggravated cyanosis , hepatic dysfunction , coagulopathy , protein loosing enteropathy , plastic bronchitis , arrhythmia etc.1 ) .
progressive decreasing cardiac output , and increasing central venous pressure can be also observed in fontan physiology with age1 ) .
most patients who underwent cardiac transplant long after fontan surgery had elevated pvr before and immediately after the operation13 ) .
indeed , pvr is an important factor in the progressive decline in efficiency of the fontan physiology .
the loss of pulsatile blood flow of pulmonary circulation of fontan patients is positively correlated with high pvr .
the lowering of pvr may increase pulmonary blood flow and preload reserve in fontan physiology , and for this reason the selective pulmonary vasodilating therapy is interesting as a means to improve the fontan circulation8 ) .
in addition , nonpulsatile pulmonary blood flow may reduce capillary recruitment and endothelial function . as a result of endothelial dysfunction , impairment in production of nitric oxide , prostacyclin and prolonged overexpression of endothelin-1 level can be observed5,14 ) .
most studies were based on high level of endothelin-1 in fontan patients9,10 ) , the endothelin receptor antagonist induced improvement of clinical , hemodynamic parameters and exercise capacity .
experiences with sildenafil therapy on fontan patients have also been reported11,12 ) . in a recent study , rhodes
et al.15 ) reported on the effect of inhaled iloprost on exercise function of fontan patients . in this article
the authors administered a single treatment with iloprost nebulizer just before exercise and concluded that iloprost improves the peak oxygen pulse and peak vo2 of patients with fontan physiology . in our two case studies
, we found that 12 weeks of iloprost therapy showed an association with improvement of clinical , hemodynamic parameters and exercise capacity in patients with fontan physiology .
first case was considered fontan failure because of aggravated doe , functional class and pitting edema .
unlike previous study using iloprost once , we used iloprost for three month period and positive results were achieved without major side effects . in addition , we found that iloprost was effective for fontan patients with or without symptoms .
although more advanced curable treatments of fontan physiology have not been developed , pulmonary vasodilator therapy on fontan circulation is one of good suggestion for symptomatic treatment of fontan failure and improvement of the cardiac output .
 decreased exercise capacity after fontan surgery is relatively common and the failure of the fontan state gradually increases with age . 
 however , there is no further treatment for patients with fontan circulation . 
 pulmonary vasodilation therapy is an effective method to solve this problem because pulmonary vascular resistance is a major factor of the fontan problem . 
 inhaled iloprost is a chemically stable prostacyclin analogue and a potent pulmonary vasodilator . 
 we experienced two cases of fontan patients treated with inhaled iloprost for 12 weeks . 
 the first patient was an 18-year - old female with pulmonary atresia with an intact ventricular septum , and the second patient was a 22-year - old male with a double outlet right ventricle . 
 fifteen years have passed since both patients received fontan surgery . 
 while the pulmonary pressure was not decreased significantly , improved exercise capacity and cardiac output were observed without any major side effects in both patients . the iloprost inhalation therapy was well tolerated and effective for the symptomatic treatment of fontan patients . 
Introduction
Case reports
1. Case 1
2. Case 2
Discussion