microRNA-206 correlates with left ventricular function after transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is the method of choice in patients with high risk or contraindications for conventional aortic valve replacement. However, it is not well understood which parameters predict the overall cardiac function postprocedurally. miRNAs are small noncoding RNA molecules that repress gene expression by different mechanisms and can also be detected in the blood. Recent studies have shown that miRNAs detected in the blood may serve as sensitive and specific biomarkers in various diseases; therefore, we examined the levels of different microRNAs in the serum of patients undergoing TAVI. We thereby intended to find potential predictors for cardiac function after TAVI. Serum from patients with aortic valve disease was obtained at five different points: before the TAVI procedure, at days 1 and 3 after the TAVI procedure, and the day of dischargement and after a period of 3 mo. We next performed quantitative real-time PCRs to examine the samples for changes in the level of miRNAs previously described as cardiac enriched. Our results show that the level of miR-206 in the serum of patients after TAVI correlated negatively with the left ventricular ejection fraction of individual patients. We found left ventricular function to be better in patients with lower levels of miR-206 after implantation of the new valve. A decrease in the serum level of miR-206 may be linked to changes in cardiac function of patients after TAVI. Further studies are necessary to test the miRNA for its potential value as a prognostic marker. NEW & NOTEWORTHY This study is the first to investigate novel miRNA-based biomarkers within the context of transcatheter aortic valve implantation. miRNA-206 proved to correlate inversely with the postprocedural left ventricular ejection fraction of patients.

[Therapy of aortic valve stenosis]. / Therapie der Aortenklappenstenose.

Calcific aortic stenosis is the most frequent valve disorder in the western world. It is a degenerative and chronic progressive disease in the elderly with increasing prevalence due to the demographic development in the population. As there is no medical therapy, the only option in severe aortic stenosis is valve replacement. Echocardiography is the diagnostic tool to assess aortic stenosis severity and morphology of the valve. Aortic stenosis is severe if the valve area is <1.0 cm(2), valve index <0.6 cm(2)/m(2) body surface, mean gradient >40 mmHg, and peak velocity >4.0 m/s. The entity of low flow, low gradient aortic stenosis is complex, and diagnosis and therapy are still challenging. Asymptomatic patients have a good prognosis, but must be reevaluated on a regular basis for the onset of symptoms or signs of progression. If one of the classical symptoms dyspnea and fatigue, angina pectoris or syncope occurs prognosis worsens dramatically and valve replacement is indicated. Gold standard therapy for aortic stenosis is surgical valve replacement. For high-risk patients (older age and severe comorbidities), transcatheter aortic valve implantation (TAVI) is established as standard therapy.

The eNOS enhancer AVE 9488: a novel cardioprotectant against ischemia reperfusion injury.

Nitric oxide (NO) is an important regulator of vascular and myocardial function. Cardiac ischemia/reperfusion injury is reduced in mice overexpressing endothelial NO synthase (eNOS) suggesting cardioprotection by eNOS. Novel pharmacological substances, so called eNOS enhancers, upregulate eNOS expression and thereby increase NO production. We tested the effects of the eNOS enhancer AVE 9488 on cardiac ischemia/reperfusion injury in vivo in mice. After treatment with the eNOS enhancer AVE 9488 (30 mg/kg/day) or placebo for one week mice underwent 30 min of coronary artery ligation and 24 h of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in mice treated with the eNOS enhancer when compared to placebo treated mice (infarct/area at risk 65.4 +/- 4.1 vs. 36.9 +/- 4.0%, placebo vs. eNOS enhancer, P = 0.0002). The protective effect was blunted in eNOS knockout mice treated with the eNOS enhancer (infarct/area at risk 64.1 +/- 6.2%, eNOS knockout + eNOS enhancer vs. WT + eNOS enhancer, P = ns). Reactive oxygen species were significantly reduced in mice treated with the eNOS enhancer as indicated by significantly lower malondialdehyde-thiobarbituric acid levels (placebo vs. eNOS enhancer, 3.2 +/- 0.5 vs. 0.8 +/- 0.07 micromol/l, P = 0.0003). Thus pharmacological interventions addressed to increase eNOS-derived NO production constitute a promising therapeutic approach to prevent myocardial ischemia/reperfusion injury.