Abstract 4143083: Cardiomyopathy in Pregnancy Complicated by Loeys-Dietz Syndrome

Case Description: A 28-year-old G2P1 woman presented at 27 weeks gestation with progressive dyspnea and lower extremity edema. She was found to have atrial fibrillation and flutter with RVR. Initial TTE revealed severely dilated left ventricle (LV) with reduced systolic function (EF 20-25%) (Figure 1). She remained in flutter despite diuresis, rate control with metoprolol and digoxin, cardioversion, and ablation. Initiation of guideline-directed medical therapy was limited by hypotension and pregnancy. She underwent a cesarean section at 32 weeks given ongoing arrhythmia and heart failure symptoms. Skin fragility and poor uterine tone were noted intraoperatively. This, in addition to her exam findings of arachnodactyly and hypertelorism, prompted genetic testing, which was positive for SMAD3 mutation consistent with Loeys-Dietz syndrome (LDS) type 3. Following delivery, spironolactone and enalapril were added in keeping with breastfeeding compatibility. Her arrhythmia burden continued to lessen. Repeat TTE showed EF of 35-40% and normal LV size. MRA of head to pelvis was notable for mild dilation of intrarenal abdominal aorta (2.5 cm) with no other vascular abnormalities. Discussion: Loeys-Dietz syndrome is an inherited connective tissue disorder caused by mutations in TGFBR 1/2, TGFB 2/3, and SMAD 3. It is characterized by multisystem involvement with cardiovascular, craniofacial, skeletal, and cutaneous features. Cardiomyopathy and arrhythmia have been described in a small number of cases. This case represents a rare manifestation of LDS diagnosed during pregnancy where hemodynamic changes likely precipitated development of symptoms and intraoperative findings, which informed additional testing and led to the diagnosis. More commonly, LDS presents with widespread arterial and aortic aneurysms that carry a high risk of dissection. Aortic dissection represents a major cause of early mortality in LDS often requiring intervention at a younger age. Complete vascular imaging is recommended at initial diagnosis, with regular surveillance thereafter. Beta blockers and angiotensin receptor antagonists are used in slowing aortic dilatation; cardiomyopathy and arrhythmias should be treated according to established guidelines.