Coronary Artery Dilation and Tortuosity in STAT3DN Hyper IgE Syndrome

Background Hyper IgE syndrome from dominant-negative STAT3 mutations is a multisystem disease with vascular complications. Following a myocardial infarction (MI) from a coronary artery aneurysm in a 43-year-old patient, our center began MRI screening for coronary vessel changes. This project aims to identify the prevalence of coronary artery dilation or tortuosity in STAT3-HIES and changes over time. Methods We reviewed coronary artery MRIs of patients with STAT3-HIES, identifying 134 patients with 345 studies from 2006 to 2025, representing 70% of our cohort. We typically repeat imaging every 3 years. Results Patients were 7–64 years (median 21) at baseline imaging and ranged from 7 to 74 years, including all studies. Seventy-six of the patients were female (57%), 122 living. At baseline imaging, 56 patients (42%) had normal-appearing coronary arteries. Tortuosity of the right coronary artery (RCA) was seen in 56 patients (42 %), and dilation of the left anterior descending coronary artery (LAD) was seen in 19 patients (14%). Eighty-eight patients had repeat imaging over 1–18 years (median 10), average 3.4 MRIs. 37 patients (42%) had imaging that worsened over time with either increased dilation or tortuosity. Three patients had myocardial infarctions related to coronary artery dilation/aneurysm; all were started on antiplatelet agents, and recurrence was seen in one patient. Hypertension occurs in about one-third of patients with STAT3-HIES. In the patients with multiple images, 5 (19%) had hypertension with normal coronary arteries over time, compared to 11 (52%) with abnormal coronary arteries but no changes over time, and 16 (44%) with worsening changes. Six patients underwent hematopoietic stem cell transplant at ages 7–20 years (median 16); three of the five with post-transplant imaging had new RCA tortuosity. Conclusions Complications from middle-sized arterial abnormalities in STAT3-HIES include subarachnoid hemorrhage from cerebral aneurysm and myocardial infarction from clot in coronary artery aneurysms. Tortuosity and dilation of the coronary arteries are common in STAT3-HIES. Patients should be screened to allow for antiplatelet therapy if a coronary artery aneurysm is present. Further study is needed regarding the role of hypertension affecting coronary artery changes and whether hematopoietic stem cell transplantation (HSCT) provides additional vascular risk.