Abstract 16870: Dickkopf-Related Protein 1, a Wingless-Regulatory Molecule, Identifies Maladaptive Left Ventricular Remodeling in Aortic Stenosis

Abstract

Introduction: Aortic stenosis (AS) may lead to left ventricular (LV) dysfunction with inadequate LV remodeling or may result in excessive LV hypertrophy. We hypothesized that circulatory Dickkopf-related protein 1 (DKK-1) as experimental regulator of myocardial repair could identify patients with a maladaptive LV response to AS. Maladaptive response may be defined by inadequate remodeling resulting in LV dysfunction or excessive hypertrophy. Methods: There were 53 adult patients demonstrated to have AS by echocardiogram or cardiac MRI completed between Jan 1st, 2016 and Dec 31st, 2017. Study patients were compared with 239 patients without AS. Patient and imaging data were collected. DKK-1 level was measured using Human DKK-1 quantikine ELISA kit. Values of DKK-1 were skewed, so non-parametric tests were used to determine the associations between DKK-1 and LV and AS parameters in echocardiography and cardiac MRI. Spearman’s Rank Order Correlation, Wilcoxon Rank Sum Test, and analysis of variance (ANOVA) were used to assess associations. Results: Among the 53 patients with AS, 29 (54.7%) were mild, 6 (11.3%) were moderate, and 18 (34%) were severe as per standard imaging criteria. In the study group, 32 (60.4%) were male, 21 (39.6%) were female, with a mean age of 72.2 years (range 47-90). In patients with AS, the median DKK-1 was 427.57 pg/mL, mean LV ejection fraction was 48.07%, mean LV mass was 147.5 g, and mean LV mass index was 69.1 g/m 2 . There was a statistically significant inverse correlation between DKK-1 and LV ejection fraction (correlation coefficient -0.28, p<0.05) only in patients with AS. There was an inverse trend of a correlation between DKK-1 and LV mass and mass index (correlation coefficient -0.3 and -0.23, respectively). There was no association between the severity of AS (aortic valve area, maximum velocity, or mean pressure gradient) and the level of DKK-1. Conclusions: In conclusion, DKK-1 might be a predictor of a maladaptive response in AS patients. In patients with elevated DKK-1 level, there is an associated diminished myocardial repair and LV dysfunction. In patients with low DKK-1 level there is a trend towards the development of accentuated LV hypertrophy. Our findings support further prospective clinical investigations of DKK-1 and other Wnt-regulatory molecules in patients with AS in the future.