Abstract 18626: Cardiac Malformations in a Pheochromocytoma and Paraganglioma Syndrome: Reconsidering the Origins of Structural Cardiovascular Disease

Abstract

Introduction: Structural cardiovascular (CV) disease and heart failure in patients with pheochromocytoma/paraganglioma is thought to develop from catecholamines and hypertension. A syndrome of polycythemia, catecholamine-releasing paragangliomas, and resultant hypertension caused by pathogenic mosaic variants in hypoxia-inducible factor 2-alpha (HIF2A or EPAS1 ) was described. Hypothesis: We hypothesized this syndrome may have both developmental and secondary causes of structural CV disease. Methods: We evaluated CV structure and function in syndromic patients (n=10), hypertensive pheochromocytoma patients without a known syndrome (n=29), and polycythemic patients (n=29) using cardiac magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) and compared their findings to normal volunteers. We also evaluated the mouse model via vascular casting and subsequent micro-CT or ex vivo 14 tesla MRI at embryonic, post-natal, and adult stages. We tested affected tissue from the mouse model for the genetic variant. Results: Compared to normal volunteers, hypertensive pheochromocytoma, and polycythemic patients, syndromic patients had enlarged left and right atrial appendages relative to respective atria (LAA/LA ratio 0.18 ± 0.04 p<0.001; RAA/RA: 0.20 ±0.10 p=0.005) [ Table ]. We observed similar abnormalities in the mouse model and confirmed the genetic variant in the affected cardiac tissue ( Figure ). Conclusions: This study identifies a signature for distinguishing primary from secondary causes of CV disease in patients with pheochromocytoma and paraganglioma using an atrial appendage to atrial volume ratio.