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Imatinib For Treatment Of Pulmonary Hypertension Associated With Gaucher Disease

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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstracts - Nadine Al-Naamani III

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Background: We describe the case of imatinib used for treatment of severe refractory pulmonary hypertension (PH) in a patient with Gaucher disease (GD) and splenectomy.

Case: A 29 year old woman with GD type 1 on enzyme replacement and remote splenectomy presented with progressive dyspnea affecting activities of daily living (New York Heart Association Functional class [NYHA FC] 4). Echocardiogram revealed normal left ventricular function with dilated right atrium and right ventricle with moderately reduced function and severe elevation of pulmonary artery pressure. Imaging (ventilation/perfusion scan and chest CT) did not demonstrate evidence of venous thromboembolism. Pulmonary function tests showed an isolated moderate reduction in diffusion capacity. She had no evidence of portal hypertension and her rheumatologic workup was unremarkable. Right heart catheterization (RHC) showed severe hemodynamic impairment and she was diagnosed with PH World Health Organization (WHO) Group 5. Intravenous treprostinil was initiated and titrated to 20ng/kg/min with improvement to NYHA FC III. The patient was intolerant of tadalafil due to laryngeal edema. The addition of ambrisentan 5 mg/day provided symptomatic improvement to NYHA FC II at 6 months; however one year, she was back to NYHA FC III. RHC showed severe hemodynamic impairment. Imatinib was added at 200 mg/day for 4 weeks and 400 mg/day thereafter and was well tolerated except for initial periorbital and facial edema, which resolved with diuresis. After 6 months, she was NYHA FC I. RHC one year later showed marked improvement. 

 

Baseline RHC

Second RHC

Third RHC

Right atrial pressure, mmHg

15/13 (11)

14/12 (11)

12/13 (9)

Pulmonary artery pressure, mmHg

90/49 (66)

89/38 (59)

61/29 (42)

Pulmonary artery wedge pressure, mmHg

12/13 (12)

20/18 (15)

25/18 (15)

Pulmonary vascular resistance, WU

13.8

10.2

3.5

Cardiac Output, L/min

3.90

4.32

7.73

Cardiac index, L/min/m2

2.26

2.50

4.42

Compassionate addition of imatinib was well tolerated and associated with significant functional and hemodynamic improvement. Our patient had 2 possible associations with PH: GD, the most common lysosomal storage disease, and splenectomy, a known risk factor for chronic thromboembolic PH (not in our patient) and PH WHO Group 5. While prostacyclins, phosphodiesterase 5 inhibitors and endothelin receptor antagonists have been used to treat PH in patients with GD, to our knowledge, this is the first report of imatinib for treatment of PH in a patient with GD and splenectomy. Imatinib, a tyrosine kinase inhibitor of platelet derived growth factor receptor was investigated as a potential treatment for PAH.

Conclusions: Imatinib was used successfully in the treatment of PH WHO Group 5 refractory to conventional PH-specific therapy.

Type: Case Study