REPLY: Sex, Gender, and Reproductive History Are Critical Variables for Spontaneous Coronary Artery Dissection Research

We appreciate the interest and thoughts from several readers regarding our article titled, “Spontaneous Coronary Artery Dissection Associated With Pregnancy.” Drs. Krittanawong and Yue highlight the challenges of International Classification of Diseases-coded research. This observation emphasizes the importance of tailoring databases to include relevant sex-based concerns to further identify and risk stratify women with cardiac disease. We agree with Drs. Elkayam and Havakuk that patients with pregnancy-associated spontaneous coronary artery dissection (P-SCAD) present with more severe disease as compared with patients with non-pregnancy-associated SCAD (NP-SCAD), and such cases can be challenging to manage.

We thank Dr. Macaya and colleagues for their thoughts. Of note, the Table 2 row heading in our paper should have read nulligravida (n = 34 in our cohort) instead of nulliparous (n = 45 in our cohort), so the comparisons performed by Dr. Macaya and colleagues do indeed include only women with prior pregnancy. The repeated exposure to the stress of pregnancy may heighten risk in vulnerable patients, and, as alluded to, this likely encompasses both the P-SCAD and NP-SCAD subgroups. Even though some aspects of the reproductive history are similar between the P-SCAD and NP-SCAD groups, the differences in severity of SCAD presentation remain significant. Of note, some of the nulligravida women were of childbearing age (mean age 45 years; range 20 to 63 years), and the women with NP-SCAD had varying exposure to exogenous hormones. Four of the nulligravida women with NP-SCAD had history of infertility treatments without subsequent pregnancy. Undoubtedly, these observations highlight the complexities of scientifically studying and understanding the role of reproductive history and ovarian hormones with regard to SCAD.

The suggestion that patients with P-SCAD may be too young to have fibromuscular dysplasia (FMD) is thought provoking. Current data suggest that FMD is for the most part a stable disease entity (1), and among patients with SCAD, imaging evaluation for FMD is recommended for all patients regardless of age or symptoms (2). However, much remains to be learned about the natural history of SCAD, FMD, and the extent of their overlapping mechanisms.