Soluble Concentrations of the Interleukin Receptor Family Member ST2 and β-Blocker Therapy in Chronic Heart Failure

Background— Concentrations of soluble (s)ST2 predict prognosis in heart failure. We recently found changing doses of β-blocker (BB) may affect sST2 concentrations. It remains unclear whether sST2 concentrations identify benefit of BB therapy, however. Methods and Results— A total of 151 subjects with heart failure attributable to left ventricular systolic dysfunction were examined in this post hoc analysis; >96% were taking BB at enrollment. Medication regimen and sST2 values were obtained during 10 months. Cardiovascular events were examined as a function of baseline sST2 status (low ≤35 versus high >35 ng/mL) and final achieved BB dose (high ≥50 versus low <50 mg daily equivalent dose of metoprolol succinate). Patients with low sST2 titrated to high-dose BB had the lowest cardiovascular event rate at 0.53 events ( P =0.001), and lowest cumulative hazard ( P =0.003). Those with low sST2/low-dose BB, or high sST2/high-dose BB had intermediate outcomes (0.92 and 1.19 events). Patients with high sST2 treated with low-dose BB had the highest cardiovascular event rate (2.08 events) and the highest cumulative hazard. Compared with low sST2/high-dose BB, those with high sST2 treated with low-dose BB had an odds ratio of 6.77 ( P <0.001) for a cardiovascular event. Patients with low sST2/low-dose BB or high sST2/high-dose BB had intermediate odds ratios for cardiovascular events ( P =0.18 and 0.02). Similar results were found for heart failure hospitalization and cardiovascular death. Conclusions— Although BB therapy exerted dose-related benefits across all study participants, sST2 measurement identifies patients with chronic heart failure who may particularly benefit from higher BB doses. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00351390.