Plasma IL-18 and IL-18BP are altered differently in reverse remodeling following aortic valve replacement.

OBJECTIVES: Patients with aortic stenosis (AS) develop left ventricular remodeling characterized by changes in extracellular matrix (ECM) and cardiomyocyte-hypertrophy. Aortic valve replacement (AVR) reverses this process (reverse remodeling). We examined plasma levels of interleukin-18 (IL-18) and its binding protein (IL-18BP) before and after AVR for AS since these mediators have been shown experimentally to exert effects on myocardial remodeling. DESIGN: Plasma levels of IL-18 and IL-18BP were analyzed in 22 patients with AS undergoing AVR, preoperatively, two days, six and 12 months postoperatively. Echocardiography and functional testing were performed. RESULTS: IL-18BP was significantly increased by 28% and 15% at two days and six months after AVR, compared to preoperative values. In contrast, IL-18 showed a later peak (increased by 24% at 12 months postoperatively) when IL-18BP was normalized. IL-18 correlated positively with deceleration time (R = 0.44) at this time-point which might indicate an association with diastolic function. CONCLUSIONS: We report for the first time that plasma IL-18 and IL-18BP are differentially regulated after AVR for AS with an early increase in IL-18BP postoperatively followed by a later peak in IL-18 at 12 months. Given the known effects of these mediators on myocardial remodeling and function, they might play a role in the reverse and remodeling process associated with AVR.

Alterations in circulating activin A, GDF-15, TGF-beta3 and MMP-2, -3, and -9 during one year of left ventricular reverse remodelling in patients operated for severe aortic stenosis.

BACKGROUND: Patients with aortic stenosis (AS) develop left ventricular remodelling with cardiomyocyte hypertrophy and increased fibrosis. Following aortic valve replacement (AVR) reverse remodelling usually takes place. AIMS: To examine circulating levels of members of the transforming growth factor (TGF) beta superfamily and matrix metalloproteinases (MMP), known to have important effects on hypertrophy and extracellular matrix, in patients operated for AS. METHODS: Circulating levels of activin A, GDF-15, TGF-beta3, MMP-2, -3, and -9 were measured in twenty-two patients undergoing AVR preoperatively, and 2 days, six months and 12 months postoperatively. Echocardiography and a six minute walking test evaluated reverse remodelling and physical performance. RESULTS: Activin A increased at six (1081.00+/-98.05 pg/ml, p<0.05) and twelve months (1263.09+/-141.43 pg/ml, p<0.05) compared to the preoperative value (855.00+/-76.30 pg/ml) and correlated negatively to physical performance. The preoperative value was also increased compared to controls (639.54+/-63.05 pg/ml, p<0.05). GDF-15, MMP-3 and -9 were all increased at two days postoperatively (p<0.05). MMP-3 correlated with left ventricular end diastolic dimension (p<0.05). MMP-2 did not change during the study period. TGF-beta3 was only slightly reduced at six months postoperatively. CONCLUSION: The observed alteration in circulating levels of members of the TGF-beta superfamily and MMPs might play a role in the reverse remodelling process following AVR for AS.

The effect of aortic valve replacement on plasma B-type natriuretic peptide in patients with severe aortic stenosis--one year follow-up.

BACKGROUND: B-type natriuretic peptide (BNP) is synthesized in cardiac tissue in response to increased wall stress and myocardial hypertrophy. AIMS: In patients with severe aortic stenosis (AS) we examined the effect of aortic valve replacement (AVR) on plasma BNP and association between BNP and left ventricular mass index (LVMI) preoperatively and in the reverse-remodeling phase twelve months postoperatively. We also examined the correlation between BNP and NYHA-class and between BNP and age. METHODS AND RESULTS: Plasma BNP analyses and echocardiographic measurements were performed preoperatively, before discharge after AVR, and at twelve months in twenty-two patients. BNP was additionally measured at six months. Preoperatively, BNP was 283+/-45 pg/ml (mean+/-SEM). Following an immediate postoperative increase (441+/-38 pg/ml), BNP values decreased towards normal values at six and twelve months (139+/-25 and 130+/-18 pg/ml, respectively). LVMI was 206.5+/-15.8 g/m(2) preoperatively and decreased to 119.7+/-7.2 g/m(2) at twelve months with a correlation between LVMI and BNP preoperatively only (r=0.45, p<0.05). There was no correlation between BNP and NYHA-class, whereas BNP correlated to age both pre- and post-operatively. CONCLUSION: We report an increase in plasma BNP in patients with AS. Following a further transient increase postoperatively, BNP levels decreased at six and twelve months after AVR. BNP correlated with LVMI preoperatively, and with age both preoperatively and at twelve months.