Impact of Pregnancy on the Natural History of Women with Hypertrophic Cardiomyopathy

Aim: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. Methods: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peripartum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events (MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure [HF] progression). Results: Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n=39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peripartum period. At 10±9 years follow-up, age at diagnosis (hazard Ratio [HR]: 1.034, 95% confidence interval [C.I.]: 1.018-1.050, p<0.001) and NYHA Class (II vs I: HR 1.944, 95% C.I. 0.896-4.218; III vs I: HR 5.291, 95% C.I. 2.392-11.705, p<0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% C.I. 0.380-0.963, p=0.034). Among women with pregnancy, multiple occurrences did not modify risk. Conclusions: Pregnancy is not a modifier of long-term outcome in women with HCM, and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.