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Both N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and soluble isoform of ST2 (sST2) have been identified as biomarkers of heart failure. We evaluated the plasma levels of NT-proBNP and sST2 in a rat model of severe aortic valve regurgitation (AR) and correlated these findings with echocardiographic measurements. We also examined the impact of omecamtiv mecarbil (OM) on these parameters. The plasma levels of NT-proBNP and sST2 were measured in 18 rats both before and 2 months after surgical induction of AR, and at these same time points, in six rats assigned to a sham-procedure control group. Plasma biomarkers were then measured again after infusion of OM or placebo in rats with AR (n=8 and 10, respectively) and OM alone in the sham control rats (n=6). Echocardiographic measurements were collected before and 2 months after induction of AR. Our results revealed increased levels of plasma NT-proBNP (219 ± 34 pg/mL vs. 429 ± 374 pg/mL; p<0.001) in rats with AR at day 7 after infusion of placebo, whereas plasma levels of sST2 were higher in this cohort after infusion of either OM or placebo. We identified a significant positive correlation between plasma sST2 with posterior wall thickness in diastole (r=0.34, p<0.05) and total body weight (r=0.45, p<0.01) in rats with surgically induced AR. Because sST2 increased markedly, whereas NT-proBNP remained unchanged, when OM was administered, we hypothesize that sST2 has a distinct capability to detect deleterious effects of passive muscle tension, not reliably assessed by NT-proBNP, in the setting of AR. [ABSTRACT FROM AUTHOR]

In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end‐systolic and end‐diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end‐systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end‐systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham‐operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR. [ABSTRACT FROM AUTHOR]