Bevacizumab, Hereditary Hemorrhagic Telangiectasia (HHT), Pulmonary Hypertension
Conditions
Keywords
hereditary hemorrhagic telangiectasia, pulmonary hypertension, bevacizumab
Brief summary
High cardiac output secondary to hepatic arteriovenous malformations may be isolated or associated with left heart failure with post-capillary pulmonary hypertension. More rarely, precapillary pulmonary hypertension develops, linked to obstructive pulmonary arterial remodeling, referred to as pulmonary arterial hypertension (PAH), which affects younger patients and is not necessarily associated with hepatic arteriovenous malformation. BEVACIZUMAB is an anti-VEGF treatment indicated under compassionate use guidelines for hereditary hemorrhagic telangiectasia in cases of symptomatic hepatic arteriovenous malformations, when complicated by isolated high cardiac output or post-capillary pulmonary hypertension, and in cases of refractory chronic bleeding. However, the efficacy of this treatment on pulmonary hypertension related to high cardiac output, isolated or associated with left heart failure, is poorly understood. In addition, this treatment is classified as a "possible association" for the development of PAH, according to the 7th World Congress Symposium on Pulmonary Hypertension. Indeed, Hlavaty et al. found, based on pharmacovigilance data and by searching for disproportionate effects using the Bayesian network method, a possible link between the use of BEVACIZUMAB and the development of PAH. This treatment is therefore not recommended in cases of PAH associated with hereditary hemorrhagic telangiectasia. The objective of this study is to investigate the efficacy and tolerability of Bevacizumab treatment in hereditary hemorrhagic telangiectasia with cardiac involvement (isolated symptomatic high cardiac output or associated with post-capillary PAH) secondary to severe liver damage, based on the experience of the French hereditary hemorrhagic telangiectasia network since the CIROCO registry was opened in 2009.
Interventions
DRUGBevacizumab
This is a retrospective observational study of patients who received Bevacizumab as part of their routine clinical care. The study will describe efficacy and tolerance outcomes based on existing data (including echocardiographic, right heart catheterization, respiratory function, biologic and clinical data before and after treatment)
Sponsors
Poitiers University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* hereditary hemorrhagic telangiectasia * treated with BEVACIZUMAB for severe liver involvement with high cardiac output (symptomatic isolated high cardiac output or associated with post-capillary pulmonary hypertension or combined pulmonary hypertension or any pulmonary hypertension) * hemodynamic data (cardiac ultrasound or right heart catheterization) within 12 months prior to the start of Bevacizumab treatment * in the French hereditary hemorrhagic telangiectasia network and registered in the CIROCO national hereditary hemorrhagic telangiectasia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac impairement before and after bevacizumab | 6 months | mean pulmonary arterial pressure (right heart catheterization) or systolic pulmonary arterial pressure (cardiac ultrasound) in mmHg before (M0) and after (M6) treatment (bevacizumab) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Outcome | 1 year | Death or hospitalization for heart failure or liver transplantation |
| Adverse effects of bevacizumab | 6 months | Adverse effects from bevacizumab such as hypertension, proteinuria, fatigue, nausea, diarrhea, joint pain, headache, dysphonia etc. |
| Right ventricular function | 6 months | Peak S wave (in cm/s) measure in ultrasound |
| peak tricuspid regurgitant velocity | 6 months | peak tricuspid regurgitant velocity (in m/s) mesured in cardiac ultrasound |
| Liver ultrasound before and after bevacizumab | 6 months | Hepatic artery diameter (in cm) |
| Clinical evolution before and after bevacizumab | 6 months | Dyspnea in NYHA |
| Cardiac output | 6 months | Cardiac output in L/min before (M0) and after (M6) treatment (bevacizumab) |
| right ventricular function | 6 months | TAPSE (in mm) measured in cardiac ultra sound |
Countries
France
Outcome results
None listed