Impact of Sildenafil Therapy on Pulmonary Arterial Hypertension
in Adults with Congenital Heart Disease
Xian-Ling Lu,1,2Chang-Ming Xiong,1Guang-Liang Shan,3Xian-Yang Zhu,4Bing-Xiang Wu,5Guang-Hua Wu,6
Zhi-Hong Liu,1Xin-Hai Ni,1Xian-Sheng Cheng,1Qing Gu,1Zhi-Hu Zhao,1Duan-Zhen Zhang,4Wei-Min Li,5
Cheng Zhang,6Hong-Yan Tian,7Ya-Juan Guo,7Tao Guo,8Hong-Min Liu,8Wei-Jun Zhang,9Hong Gu,9
Shi-An Huang,10Jian-Ying Chen,10Wei-Feng Wu,11Kai Huang,11Jian-Jun Li1& Jian-Guo He1
1Center for Diagnosis and Management of Pulmonary Vascular Diseases, Department of Cardiology, Cardiovascular Institute and Fu Wai Hospital, Chinese
Academy of Medical Sciences & Peking Union Medical College, Beijing, China
2The First Affiliated Hospital, Shihezi Medical College, Xinjiang, China
3Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
4General Hospital of Shenyang Military Region, Liaoning, China
5The First Affiliated Hospital, Haerbin Medical University, Heilongjiang, China
6The First Affiliated Hospital, Jining Medical College, Shandong, China
7The First Affiliated Hospital, Xi’an Medical University Shanxi, China
8The First Affiliated Hospital, Kunming Medical College, Yunnan, China
9Anzhen Hospital, Capital Medical College, Beijing, China
10The First Affiliated Hospital, Guangdong Medical College, Guangdong, China
11The First Affiliated Hospital, Guangxi Medical College, China
Adults; Congenital heart disease; Pulmonary
arterial hypertension; Sildenafil.
Dr. Jian-Guo He, M.D., Ph.D., or Dr. Jian-Jun Li,
M.D., Ph.D., Department of Cardiology, Fu Wai
Hospital, Chinese Academy of Medical Sciences
and Peking Union Medical College, 167 BeiLiShi
Road, Beijing 100037, China.
Tel.: 86-10-88398060 or 86-10-88396077;
E-mail: email@example.com or
Background: It has been demonstrated that sildenafil is effective in patients with pul-
monary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults
with congenital heart disease (CHD) has been less investigated. Objective: In this prospec-
tive, open-label, uncontrolled and multicenter study, 60 patients with PAH related to CHD
received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six-
minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the
12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT;
the secondary end point included assessment of functional class, evaluation of cardiopul-
monary hemodynamics, and clinical worsening (defined as death, transplantation, and re-
hospitalization for PAH). Drug safety and tolerability were also examined. Results: Oral
sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m,
P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32
vs. 2.57 ± 1.42, P = 0.0307). Moreover, significant improvements in World Healthy Orga-
nization (WHO) functional class and cardiopulmonary hemodynamics were also discovered
(mean pulmonary artery pressure, P = 0.0002; cardiac index, P < 0.0001; pulmonary vascu-
lar resistance, P < 0.0001). Side effects in this study were mild and consistent with reported
studies. None of the enrolled patients experienced significant clinical worsening. Conclu-
sions: This study confirmed and extended previous studies. It suggested that oral sildenafil
was safe and effective for the treatment of adult patients with CHD-related PAH.
Pulmonary arterial hypertension (PAH) of variable degree is com-
monly associated with adult heart disease . It has been reported
that 5–10% of patients with congenital heart disease (CHD) de-
velop PAH of variable severity [2,3]. Despite recent advancements
in the diagnosis and cardiac surgery for CHD, a significant number
of CHD patients still develop PAH, which impacts negatively on
the life quality and even the survival of these adult patients. This is
especially the case with patients who develop near-systemic pul-
monary arterial pressures (Eisenmenger syndrome) [4–6]. Even
for patients who go through surgical correction of large systemic-
to-pulmonary shunts in infancy, PAH can still be developed in
some patients postoperatively .
Recently, improved disease-targeting therapies for PAH have led
to a renewed interest in this condition and stood to benefit a large
number of patients with CHD [8–12]. However, patients with CHD
are underrepresented in most trials of advanced PAH therapies.
Cardiovascular Therapeutics 28 (2010) 350–355c ?2010 Blackwell Publishing Ltd
X.-L. Lu et al.
Impact of Sildenafil on PAH in CHD
study (12 weeks) may not be enough to fully elucidate the possible
effect of sildenafil on CHD-associated PAH in adults.
Financial disclosure: This study was supported by National
Grant (the Eleventh 5-year Plan of Social and Economic Develop-
ment in China Improve the Diagnosis and Therapy of Pulmonary
Hypertension in China, 2006BAI01A07) from the Ministry of Sci-
ence and Technology, and Capital Development Scientific Fund
(Study of Guideline in Pulmonary Hypertension Diagnosis and
Management, 2005–1081) the People’s Republic of China.
Dr. Xian-Ling Lu collected and analyzed data and prepared the
primary manuscript. Dr. Jian-Jun Li interpreted the data and pre-
pared the final manuscript. Dr. Jian-Guo He designed the project
as the principle investigator for the study. All other authors who
are listed yet not specially acknowledged contributed to the acqui-
sition of subjects and data.
We would like to thank Pfizer Pharmaceuticals Limited for supply-
ing each of the recruited patients one month worth of medicine for
Conflict of Interest
The authors have no conflict of interest.
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Cardiovascular Therapeutics 28 (2010) 350–355c ?2010 Blackwell Publishing Ltd