Successful use of aflibercept for high cardiac output in hereditary hemorrhagic telangiectasia after failure of pazopanib and bevacizumab therapy.

Hereditary hemorrhagic telangiectasia (HHT) can manifest with hepatic arteriovenous malformations, leading to a high cardiac output state and pulmonary hypertension. Bevacizumab is commonly used to treat this complication, but response is often partial and may diminish over time. We present a patient with ACVRL1-related HHT and high cardiac output who failed pazopanib and developed apparent bevacizumab resistance with symptom recurrence despite maintenance and reintroduced therapy. Aflibercept, a vascular endothelial growth factor and placental growth factor-binding decoy receptor, was initiated intravenously, resulting in improved dyspnea, decreased epistaxis severity, and a reduction in cardiac index from 3.92 to 2.90 L/min/m2. Hemoglobin and iron indices remained stable without transfusion or iron support. This case highlights aflibercept as a potential alternative antiangiogenic agent for HHT-related high-output states following bevacizumab failure. Mechanistic distinctions between these agents and prior reports of aflibercept efficacy in other refractory vascular contexts suggest a role for broader investigation.