Long telomere length in circulating leukocytes is associated with monocytosis and poorer survival in patients with transcatheter aortic valve replacement

Abstract

Abstract Background Whiletranscatheter aortic valve replacement (TAVR) has become a standard treatment option in the management of patients with severe aortic stenosis and higher risk for cardiac surgery, occurrence of a systemic inflammatory response after TAVR limits patients' prognosis. Leukocyte telomere length (LTL) is an established marker of cellular senescence and longer telomeres are hallmarks of immune competence and inflammatory responsiveness of leukocyte subsets. In the present study, we assessed LTL and its impact on 2-year survival in patients (pts) following TAVR. Methods and results LTL was analyzed using quantitative real-time PCR in 285 consecutive pts (mean age 80.9 years, 49% male) undergoing TAVR and correlated with 2-year all-cause mortality (46 deaths, 16%). Kaplan-Meier survival curves showed that the highest compared to lowest tertile of LTL was associated with an increased rate of all-cause mortality (log rank p=0.03). Multivariate regression model revealed higher EuroSCORE 2 (HR: 1.03, 95% CI: 1.01–1.05; p=0.021) and long LTL (HR: 1.001, 95% CI: 1.001–1.001; p=0.023) to be independent predictors for 2-year mortality, after adjustment for clinical variables such as age, sex, cardiovascular risk factors, LVEF and renal function. When analyzing blood leukocyte subset composition, pts in the highest LTL tertile showed significantly higher levels of circulating neutrophils (p=0.011) and monocytes (p=0.011), whereas there was no significant correlation between LTL and lymphocyte counts (p=0.12). Conclusion In elderly patients with severe aortic valve stenosis, long leukocyte telomere length is associated with increased mortality after TAVR. This might be explained by enhanced immune competence and increased pro-inflammatory leukocyte function in these patients as indicated by significant monocytosis, which might drive systemic inflammatory response syndrome or chronic inflammation and limit the prognosis in TAVR patients. Funding Acknowledgement Type of funding source: None