Elevated suppression of tumorigenicity 2 receptor is associated with poor outcome in heart failure with preserved ejection fraction

Background Soluble suppression of tumorigenicity 2(sST2) receptor is a well-known biomarker implicated in inflammatory diseases. It has already been shown that sST2 is associated with worse outcome in HFrEF. Objective We sought to evaluate the association of sST2 with clinical, laboratory and imaging findings and its prognostic value in HFpEF. Methods Between January 2015 and June 2017, we prospectively enrolled 137 consecutive HFpEF patients (79 ± 8 years, 61% women). Elevated sST2 was determined by an age and sex-adjusted cutoff value (55 ng/ml) corresponding to mean + 2 SD in 31 controls (75 ± 6years, 61% women). All patients underwent complete 2D echo and cMR and were followed up for a composite outcome of mortality and first HF hospitalization. Results Median sST2 level was 44.5 ng/ml (IQR: 31.6–62.2 ng/ml). Elevated sST2 patients (n = 46) had an impaired right ventricular (RV) function (FAC 39 ± 10% vs. 43 ± 8%, P = 0.017; RVEF by cMR 53.5 ± 9.8% vs. 58.1 ± 7.8%, P = 0.008) and a higher proportion with pathologic RV/RA gradient (n = 20 (40%) vs. n = 23 (26%), P = 0.034). They were similar for other clinical, laboratory and imaging characteristics. Multivariate logistic analysis showed that only RVEF by cMR was associated with high sST2 level (OR: 0.94 [0.89–0.99], P = 0.010). During a mean follow-up of 20 ± 8months, 71 patients (52%) reached the combined end point. Cox analysis identified GFR, hemoglobin, sST2, use of loop diuretic and E/e’ ratio as significant predictors of outcome. Only GFR (HR = 0.98 [0.96–0.99], P Kaplan Meier event free survival curve showed that high sST2 HFpEF patients had poorer prognosis than low sST2 patients (P = 0.001, Fig. 1 ). Conclusions In HFpEF, sST2 is associated with impaired RV function and with a poorer prognosis with higher rate of mortality and first HF hospitalization.