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Objectives Cathepsin D has been implicated in the development of preeclampsia and peripartum cardiomyopathy. We sought to examine the association of cathepsin D with cardiac dysfunction on echocardiography in women with preeclampsia. Methods Preeclamptic women aged 18–43 were recruited for this IRB approved study. Demographics, clinical data, and outcomes were recorded throughout the antepartum and postpartum course. Serum for cathepsin D activity and placental growth factor (PlGF) was drawn at the time of clinical labs. PlGF (pg/ml) was determined using ELISA. Cathepsin D activity (μM) was determined using a fluorimetric Sensolyte® 520 Immunoassay. Bedside transthoracic echocardiography was performed antepartum and postpartum for determination of standard myocardial function parameters as well as myocardial strain with speckle tracking. Statistical analyses included t -test, ANOVA, and pairwise correlations. Results We enrolled 23 women with mild ( n = 10) and severe ( n = 13) preeclampsia. Echocardiography was available antepartum on 21 women (strain imaging on 8) and postpartum on 17 women (strain imaging on 11). Mean age was 28.7 ± 5.6 years. Most women were Caucasian ( n = 21) and primigravida ( n = 14). Average gestational age at enrollment was 32.0 ± 4.8 weeks. Increasing ratio of cathepsin D activity to PlGF was associated with worsening longitudinal strain antepartum ( p = 0.02). Postpartum, increasing ratio of cathepsin D to PlGF was associated with decreasing fractional shortening ( p = 0.02). Conclusions Ratio of cathepsin D activity to PlGF is associated with subclinical cardiac dysfunction as determined by speckle tracking for cardiac strain as well as fractional shortening on echocardiography. A ratio of cathepsin D activity to PlGF as a marker of anti-angiogenic factors to pro-angiogenic balance better indicates this association than cathepsin D activity alone. Disclosures C.F. Pearce: None. G.S. Dhaliwal: None. M. Keihanian: None. S. Mast: None. R.I. Pollack: None. J.M. O’Brien: None. W.F. Hansen: None. T.E. Curry: None. A.L. Bailey: None.