Abstract 4333: Non-Myocardial Production of ST2 Protein in Human Cardiac Hypertrophy and Failure is Related to Diastolic Load
ST2 is a member of the Toll-interleukin-1 receptor family currently under investigation as a novel serum marker of heart failure (HF).
Aim. To investigate
the relationship between serum ST2 levels and hemodynamic and neurohumoral factors;
the myocardium as the source of ST2 production in human cardiac hypertrophy and failure.
Serum levels of ST2, Nt-pro BNP, and CRP were measured (ELISA) in 45 patients (pts) with aortic stenosis (AS), 53 pts with congestive cardiomyopathy (CCM), and 23 controls with normal LV function (C). LV hemodynamics were assessed at catheterization and echocardiography within 24 hours of blood sampling. Myocardial production of ST2 and Nt-pro BNP were assessed from concentration differences following coronary sinus and intraventricular sampling in 24 pts with CCMP. (Table⇓, Kruskal-Wallis or ANOVA, and post-hoc statistics. *, p<0.05 vs C; **p<0.01 vs C). Serum ST2 levels (pg/mL; median [25th–75th]) were elevated in AS and CCM vs. C and were significantly correlated with Nt-pro BNP (r=0.47; p<0.0001) and CRP (r=0.55; p<0.01). Among hemodynamic variables (mean±SEM), ST2 levels were positively correlated with EDP (r=0.38, p<0.05) and LV diastolic wall stress (diaWS, r=0.28 p<0.05) but not with other hemodynamic variables, including indices of systolic load. Serum ST2 was significantly higher in pts with isolated diastolic heart failure (diastolic HF, N=14) compared to Controls (383±149 vs. 75±12 pg/mL, p<0.01). Arterial vs coronary sinus levels of Nt-pro BNP were 1069±191 and 1798±241 pg/mL with a difference of +729±84 pg/mL, p<0.0001, and of ST2 were 275±40 and 264±35 pg/mL with a differences of −11±8 pg/mL, p=NS, demonstrating myocardial production of Nt-pro BNP but not of ST2. In human hypertrohy and failure, serum ST2 is elevated and correlates with diastolic load. Unlike Nt-pro BNP, the source of circulating serum ST2 is extra-myocardial.