Efficacy and Tolerance of Treatment With Bevacizumab for Severe Liver Involvement With High Cardiac Output in Hereditary Hemorrhagic Telangiectasia Within the French Hereditary Hemorrhagic Telangiectasia Network (BevaHHearT)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pulmonary Hypertension; Bevacizumab; Hereditary Hemorrhagic Telangiectasia (HHT)
• Intervention / Treatment: Drug: Bevacizumab

• Study Type: Observational
• Enrollment (Estimated): 111

Contacts and Locations

Study Locations

• France
  • Poitiers, France, 86000
    • Centre Hospitalier Universitaire de Poitiers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with hereditary hemorrhagic telangiectasia who have received treatment with BEVACIZUMAB for severe liver involvement with high cardiac output in hereditary hemorrhagic telangiectasia within the French hereditary hemorrhagic telangiectasia network and registered in the CIROCO national hereditary hemorrhagic telangiectasia registry

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

hereditary hemorrhagic telangiectasia patients; Adult patients with hereditary hemorrhagic telangiectasia who have received treatment 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) in hereditary hemorrhagic telangiectasia within the French hereditary hemorrhagic telangiectasia network and registered in the CIROCO national hereditary hemorrhagic telangiectasia registry and having hemodynamic data (cardiac ultrasound or right heart catheterization) within 12 months prior to the start of Bevacizumab treatment

Drug: Bevacizumab; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac impairement before and after bevacizumab	mean pulmonary arterial pressure (right heart catheterization) or systolic pulmonary arterial pressure (cardiac ultrasound) in mmHg before (M0) and after (M6) treatment (bevacizumab)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outcome	Death or hospitalization for heart failure or liver transplantation	1 year
Adverse effects of bevacizumab	Adverse effects from bevacizumab such as hypertension, proteinuria, fatigue, nausea, diarrhea, joint pain, headache, dysphonia etc.	6 months
Right ventricular function	Peak S wave (in cm/s) measure in ultrasound	6 months
peak tricuspid regurgitant velocity	peak tricuspid regurgitant velocity (in m/s) mesured in cardiac ultrasound	6 months
Liver ultrasound before and after bevacizumab	Hepatic artery diameter (in cm)	6 months
Clinical evolution before and after bevacizumab	Dyspnea in NYHA	6 months
Cardiac output	Cardiac output in L/min before (M0) and after (M6) treatment (bevacizumab)	6 months
right ventricular function	TAPSE (in mm) measured in cardiac ultra sound	6 months

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 28, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 28, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: bevacizumab; pulmonary hypertension; hereditary hemorrhagic telangiectasia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Hypertension; Vascular Malformations; Telangiectasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hypertension, Pulmonary; Telangiectasia, Hereditary Hemorrhagic; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: BevaHHearT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No