Aims

Aortic valve stenosis (AVS) is caused by active pro-inflammatory and calcifying remodelling. Chronic kidney disease (CKD) is a very frequent comorbidity. Circulating chaperones have emerged as both effectors and prognostic markers for various diseases, including cardiovascular disease. The aim of this study was to investigate the role of circulating chaperones in patients with severe AVS undergoing transcatheter aortic valve replacement (TAVR).

Methods and Results 

We included 159 consecutive patients who underwent TAVR. We determined serum levels Glucose-regulated protein 78 (GRP78) and heat shock protein 27 (HSP27) by ELISA kits. The primary end point was defined as one-year mortality. Patients with lower levels of circulating GRP78 (<1347 ng/ml) had an increased one-year mortality rate compared to patients with higher levels of GRP78 (25.0% vs. 10.3%, p=0.026). GRP78 was associated with lower one-year mortality in a univariate analysis (HR 0.354, p=0.047). After adjusting for age, sex, several comorbidities and biomarkers, GRP78 (HR 0.366, p = 0.049) and CKD (HR 2.788, p = 0.046) remained independent predictors of the primary end point in a multivariate analysis. Patients with concomitant CKD had significantly higher levels of HSP27 compared to patients without CKD (1690 pg/ml vs 1076 pg/ml, p = 0.0109). HSP27 was not associated with the primary end point in the overall cohort, but in patients with CKD, elevated HSP27 was identified as a protective marker (one-year mortality: 9.6% vs. 31.4%, log-rank p = 0.0166). Using cut-off values for GRP78 and HSP27 we were able to stratify patients with CKD undergoing TAVR into four groups with distinct mortality rates (50% vs. 22.2% vs. 24% vs. 7.9%, log-rank p=0.0170)

Conclusion

GRP78 is an overall predictor of mortality after TAVR, while the combination of GRP78 and HSP27 helps to predict mortality in patients with CKD receiving TAVR. These results suggest that there are protective properties of circulating chaperones in valvular inflammation and calcification.