At the Heart of the Matter - Speckle Tracking Echocardiography in Lupus Mothers and Their Offspring

Women with SLE have a high risk of placenta-mediated adverse pregnancy outcomes (APO), including gestational hypertension, preeclampsia, eclampsia, small for gestational age (SGA) neonate, placental abruption, and stillbirth. It is hypothesized that high levels of circulating anti-angiogenic factors, placental microparticles, and other soluble mediators cause endothelial dysfunction and lead to cardiovascular diseases (CVD) in women with APO. In women with SLE, CVD is the leading cause of death, accounting for almost half of all deaths.Until now, studies have been unable to identify the cause of increased CVD in SLE women, despite accounting for SLE disease activity, damage, and drugs. Given the huge burden of CVD in SLE, it is unfathomable that no one has, to date, comprehensively examined the relationship between APO and CVD risk in SLE women.

Importantly, the offspring of mothers with placenta-mediated complications also have an increased CVD risk and in SLE offspring, in-utero exposure to maternal autoantibodies might further contribute to increased CVD risk.

Hydroxychloroquine (HCQ), the cornerstone drug in SLE treatment, may prevent SLE flare during pregnancy and reduces the risk of APO. However, HCQ may pose cardiotoxicity. HCQ dosing is done by weight but surprisingly, drug level monitoring is almost non-existent in Canada, although it is increasingly championed by key opinion leaders in the US and Europe. Lack of drug level monitoring is particularly concerning during pregnancy, given potential risks to mother and baby for adverse outcomes related to under or potentially overdosing. The incidence and prevalence of HCQ cardiotoxicity are not known and it is likely to be an under-diagnosed complication as patients are not systematically screened. Furthermore, data are urgently needed to address cardiac safety in neonates exposed to HCQ.

To assess cardiac function (i.e., myocardial contraction and relaxation), the investigators will use global longitudinal strain (GLS) measured by speckle tracking echocardiography (STE). GLS has superior prognostic value to conventional measures such as the left ventricle ejection fraction (LVEF) for predicting major adverse cardiac events and provides incremental prognostic information beyond the traditional CVD risk stratification tools. Moreover, GLS assessed by STE has most consistently detected early myocardial changes during therapy and appears to be the best measure of early drug cardiotoxicity, predicting future reduction in LVEF or heart failure.

The investigators will test the hypothesis that SLE women with APO have higher frequency of impaired myocardial strain versus SLE women without APO. The investigators will also evaluate the hypothesis that exposure to maternal autoantibodies during pregnancy (ie anti-Ro/La and aPL) is associated with impaired myocardial strain in neonates (versus unexposed neonates). Another hypothesis is that maternal and cord HCQ levels correlate with impaired myocardial strain in mothers and neonates respectively, potentially following a J-curve relationship (i.e. lower HCQ levels failing to be cardio-protective against maternal autoantibodies and higher HCQ levels leading to cardiotoxicity).