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

Abstract

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/lowdose 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.

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“…In this same cohort, sST2 concentrations were found to interact with β-adrenergic blocker therapy. 141 …”

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“…Similarly, the highsST2 group benefited most from beta-blocker therapy in other settings. 37,38) sST2 might be used to help clinicians with decision-making and it is also a potential therapeutic target.…”

Preliminary study of beta-blocker therapy on modulation of interleukin-33/ST2 signaling during ventricular remodeling after acute myocardial infarction

“…However, the expected benefits of b-blocker therapy in those with elevated concentrations of sST2 have been elusive. The recent PROTECT study has shown that chronic systolic HF patients with lower ST2 levels are likely to get the most benefit from higher b-blocker doses [20]. While this report is encouraging, the putative link between ST2 and the cardioprotective effect of b-blocker therapy requires further clarification.…”