Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) pressure overload which leads to myocardial remodeling and heart failure. In these patients inflammatory biomarkers are known to be increased and of prognostic relevance. In detail Interleukin 6 (IL6) is secreted as an early response to infection and tissue damage. C-reactive protein (hsCRP) is a highly sensitive marker, which is subsequent to IL6 in the same pathway. Both have been described as a prognostic factor for incident cardiovascular events. Growth differentiation factor 15 (GDF-15) is a cytokine of the transforming growth factor superfamily that is upregulated in response to myocardial dilation and LV pressure overload in severe AS. Serum levels of mid-regional pro-adrenomedullin (MR-proADM) have also been found to be increased in cases of heart failure. Transcatheter aortic valve implantation (TAVI) has implemented as treatment option for symptomatic patients with severe AS. The primary aim of the present study was to examine the effect of TAVI on the overall inflammatory response by analyzing IL6, hsCRP, MR-proADM and GDF-15. In addition, the predictive value of all-cause mortality of these biomarkers was evaluated in these patient cohort.

Methods: A total of 91 consecutive patients (mean age: 80,8 [±5,3] years) undergoing TAVI were included in this study. TAVI was performed according to standard clinical practice. Venous blood samples for biomarker analysis were collected prior to and 6 months after TAVI, these were processed immediately and frozen at -80 °C until the assay was performed. Safety events, physiological- and echocardiographical parameters, including the New York Heart Association (NYHA) class, were assessed at the baseline and the 6-month follow-up. Furthermore, we compiled the all-cause mortality of our patients after two years.

Results: TAVI was performed successfully in all patients. During the two-year follow-up period 24 patients met the endpoint of all-cause mortality. At baseline, serum levels of the inflammatory biomarkers were significantly higher in patients who died within the follow-up period, when compared to survivors (IL6:14,450pg/ml [IQR:7,550;42,150] vs. 4,200pg/ml [IQR:2,515;13,875],p=0,0004; hsCRP:5,360 mg/l [IQR: 2,248;26,790] vs. 2,900mg/l [IQR:1,208;8,210],p=0,022); MR-proADM:1,347nmol/l [IQR:1,038-1,678] vs. 0,922nmol/l [IQR:0,706; 1,202],p=0,0003 and GDF-15:2770,0pg/ml [IQR:2401,0;3701,0] vs. 1675,2pg/ml [IQR:1141,6;2524,4],p=0,001). The area under the curve was 0,767 for IL-6, 0,665 for hsCRP, 0,735 for MR-proADM and 0,735 for GDF-15. In addition, there was a significant decrease of IL-6 (baseline: 4,200pg/ml [IQR:2,525;13,875] vs. 6FU:2,600pg/ml [IQR:1,500;7,000],p<0,0001), hsCRP (baseline:2,900mg/l [IQR:1,208; 8,210] vs. FU: 2,101 mg/l [IQR: 0,980; 4,540],p=0,002) and MR-proADM (baseline:0,922nmol/l [IQR:0,706-1,202] vs. FU: 0,828nmol/l [IQR:0,642-1,132],p=0,01) serum levels in survivors after a follow-up of 6 months after TAVI, when compared to baseline values. While the median serum levels of GDF-15 (baseline:1675,2pg/ml [IQR:1141,6;2524,4] vs. FU: 1663,8pg/ml [IQR:1176,5;2538,1],p=0,563) remained stable.

Conclusions: In the present study there was a significant decrease of inflammatory biomarkers after TAVI in high risk patients with severe aortic stenosis and good clinical outcome. In this regard, IL-6, hsCRP, MRproADM and GDF-15 were predictors of all-cause mortality in patients, who underwent TAVI.