Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 51, Issue 11, Pages -Publisher
WILEY
DOI: 10.1111/eci.13595
Keywords
aortic valve stenosis; deoxyribonuclease; extracellular DNA; transcatheter aortic valve replacement
Funding
- Paracelsus Medical University of Salzburg [R-19/05/125-FEJ]
- Austrian Science fund FWF [F54]
- Austrian Science Fund (FWF) [F54] Funding Source: Austrian Science Fund (FWF)
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This study investigated the levels of double-stranded DNA and deoxyribonuclease activity in plasma after TAVR, finding that baseline double-stranded DNA was significantly higher compared to healthy controls, peaked at 3 and 7 days post-TAVR, and then declined. Additionally, decreased deoxyribonuclease activity at baseline was associated with higher C-reactive protein levels and mean transaortic gradient after 12 months, serving as a strong independent predictor of outcome post-TAVR.
Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.
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