Outcome of Bosentan treatment in Outcome of Bosentan treatment in patients with pulmonary arterial patients with pulmonary arterial

hypertension associate with congenital hypertension associate with congenital heart diseaseheart disease

Hong Gu, MD. PhDHong Gu, MD. PhD

Department of Pediatric CardiologyDepartment of Pediatric CardiologyBeijing Anzhen HospitalBeijing Anzhen Hospital

Beijing, ChinaBeijing, Chinakoko_gu@yahoo.comkoko_gu@yahoo.com

BackgroundBackground

1. Bosentan is known as a safe and effective 1. Bosentan is known as a safe and effective vasodilators in vasodilators in

patients with idiopathic pulmonary hypertension patients with idiopathic pulmonary hypertension (IPAH). (IPAH).

2. Evidences of Bosentan used in patients with PAH 2. Evidences of Bosentan used in patients with PAH associated with unrepaired congenital heart disease associated with unrepaired congenital heart disease are limited.are limited.

PurposePurpose

Describe the safety and effectivity Describe the safety and effectivity of Bosentan used in patients with of Bosentan used in patients with PAH-CHD.PAH-CHD.

MethodsMethods

1. A monocentre, open-label, uncontrolled, observational 1. A monocentre, open-label, uncontrolled, observational study was conducted.study was conducted.

2. 32 patients with PAH associated with unrepaired CHD 2. 32 patients with PAH associated with unrepaired CHD were treated with bosentan as monotherapy (n=26) were treated with bosentan as monotherapy (n=26)

or or as an add-on to pre-existing oral Sildenafil (n=6), as an add-on to pre-existing oral Sildenafil (n=6), bbetween etween Janurory 2008 Janurory 2008 and and May 2011.May 2011.

3. The diagnosis was conformed by echocardiogram, and 3. The diagnosis was conformed by echocardiogram, and cardiac catheterizition.cardiac catheterizition.

4. NYHA functional class, 6-minute walk distance 4. NYHA functional class, 6-minute walk distance (6MWD)(6MWD)

and SPOand SPO2 2 were assessed before starting bosentan treatment and during follow-up.

5. Hemodynamic parameters (mPAP, Qp/Qs, PVRI, 5. Hemodynamic parameters (mPAP, Qp/Qs, PVRI, and and

Rp/Rs) were obtained by cardiac catheterization Rp/Rs) were obtained by cardiac catheterization in all in all

the patients before Bosentan treatment and the the patients before Bosentan treatment and the follow up cath in some of the patients.follow up cath in some of the patients.

MethodsMethods

Patient Data

Male/Female 9/23 Male/Female 9/23

Age (years) 13.5±8.2Age (years) 13.5±8.2 Adult/Pediatric 9/23 Adult/Pediatric 9/23

Mean duration of therapy (months) 13.3±9.9Mean duration of therapy (months) 13.3±9.9

（（ range 2.1-35.9range 2.1-35.9 ））

（（ range 3-51range 3-51 ））

DiagnosisDiagnosis

VSD 12VSD 12

ASD 3 ASD 3

PDA 5PDA 5

VSD+ASD 4VSD+ASD 4

VSD+PDA 3VSD+PDA 3

ASD+PDA 1ASD+PDA 1

VSD+ASD+PDA 3VSD+ASD+PDA 3

TECD+PDA 1TECD+PDA 1

Clinical Response to therapy

SpO2% 32 89±5 91±5 0.002 SpO2% 32 89±5 91±5 0.002 ﹡﹡

6MWT(m) 19 452±86 482±71 0.004 6MWT(m) 19 452±86 482±71 0.004 ﹡﹡ (age older than 7 years)(age older than 7 years)

NYHA-FCNYHA-FC

I 0 1 0.011 I 0 1 0.011 ﹡﹡ II 25 30 II 25 30

III 5 1 III 5 1

IV 2 0IV 2 0

N Baseline After treatment PN Baseline After treatment P

Demographics of patients with twice cardiac catheterization

Male/Female 4/10Male/Female 4/10

Age (years) 13.2±9.2Age (years) 13.2±9.2 （（ 2.1-2.1-36.236.2 ））

Mean duration of therapy (months) 9.3±4.2Mean duration of therapy (months) 9.3±4.2 （（ 5.3-5.3-20.520.5 ））

N=14N=14

Changes of hemodynamic Changes of hemodynamic parametersparameters

mPAP (mmHg) 77±6 77±16 0.832mPAP (mmHg) 77±6 77±16 0.832

PVRI (WUPVRI (WU··MM22) 22.9±10.5 20.7±11.5 0.257) 22.9±10.5 20.7±11.5 0.257

Qp/Qs 0.98±0.3 1.3±0.6 0.011Qp/Qs 0.98±0.3 1.3±0.6 0.011

﹡﹡

Rp/Rs 0.98±0.29 0.86±0.37 0.198Rp/Rs 0.98±0.29 0.86±0.37 0.198

TPR 28.8±17.4 23.2±12.7 0.09TPR 28.8±17.4 23.2±12.7 0.09

N=14 Before After PN=14 Before After P

Side effectsSide effects

1. No abnormal liver function 1. No abnormal liver function 2. No systemic hypotension2. No systemic hypotension3. Two patients had hematochezia (fresh blood on the 3. Two patients had hematochezia (fresh blood on the surface).surface).

No1 No1 (10 years old boy, VSD+PDA, treated with Bosentan (10 years old boy, VSD+PDA, treated with Bosentan

and Sidenafil), was diagnosed as ulcerative colitis by and Sidenafil), was diagnosed as ulcerative colitis by

colonoscope. colonoscope. No2 (25 years old young lady, huge VSD, treated only with Bosentan) Both of them recovered by reducing the dose of Bosentan, they are all still on Bosentan treatment now.

Side effectsSide effects

ConclusionConclusion

1. All patients alived during treatment of Bosentan.1. All patients alived during treatment of Bosentan.

2. Bosentan was well tolerated by all patients with 2. Bosentan was well tolerated by all patients with PAHPAH

related to unrepaired CHD, even in chidren.related to unrepaired CHD, even in chidren.

2. Bosentan caused significant improvements in2. Bosentan caused significant improvements in

6MWD6MWD 、 、 NYHA-FC NYHA-FC 、 、 SpOSpO22..

3. Bosentan significantly increased Qp/Qs, reduced 3. Bosentan significantly increased Qp/Qs, reduced thethe

PVRI, TPR and Rp/Rs.PVRI, TPR and Rp/Rs.

4. There is a potential for side effect like bleeding.4. There is a potential for side effect like bleeding.

Thank you very much!