Hoffmann Jedrzej, Tabata Noriaki, Mas-Peiro Silvia, Spyridopoulos Ioakim, Sinning Jan-Malte, Berkowitsch Alexander, Martin-Ruiz Carmen, Al-Kassou Baravan, Herrmann Eva, Dimmeler Stefanie, Zeiher Andreas M, Vasa-Nicotera Mariuca
Department of Medicine, Cardiology, Goethe University Hospital, Frankfurt, Germany.
Department of Medicine II, Heart Center Bonn, University Hospital Bonn, Bonn, Germany.
Eur Heart J Open. 2022 Jul 23;2(4):oeac045. doi: 10.1093/ehjopen/oeac045. eCollection 2022 Jul.
Inflammatory activation of leukocytes may limit prognosis of patients (pts) with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Leukocyte telomere length (LTL) is a marker of proliferative capacity and inflammatory responsiveness but the impact of LTL on the prognosis in AS remains elusive. The aim of this study was to analyse the association of LTL with inflammatory markers and prognosis of pts undergoing TAVR.
LTL was analysed using quantitative real-time PCR in 285 consecutive pts (median age 82 years) undergoing TAVR and correlated with 18-month all-cause mortality. C-reactive protein was significantly elevated in pts with the longest LTL ( = 0.017), paralleled by increased procalcitonin (PCT) serum levels ( = 0.0006). This inflammatory reaction was accompanied by increased myeloid cells in the highest LTL tertile, mainly a rise in circulating neutrophils ( = 0.0025) and monocytes ( = 0.01). Multivariate analysis revealed LTL (HR 2.6, 95%CI 1.4-5.1, = 0.004) and PCT levels (HR 4.3, 95%CI 1.7-11.0, = 0.003) as independent predictors of mortality.
Longer LTL is associated with increased mortality after TAVR. This might be explained by enhanced proliferative capacity of cells resulting in myeloid and systemic inflammation. Our findings suggest that targeting the specific inflammation pathways could present a novel strategy to augment survival in selected patients with degenerative aortic stenosis.
白细胞的炎症激活可能会限制严重主动脉瓣狭窄(AS)患者接受经导管主动脉瓣置换术(TAVR)后的预后。白细胞端粒长度(LTL)是增殖能力和炎症反应性的标志物,但LTL对AS患者预后的影响仍不明确。本研究的目的是分析LTL与接受TAVR患者的炎症标志物及预后之间的关联。
对285例连续接受TAVR的患者(中位年龄82岁)采用定量实时PCR分析LTL,并将其与18个月的全因死亡率相关联。LTL最长的患者中C反应蛋白显著升高(P = 0.017),同时降钙素原(PCT)血清水平也升高(P = 0.0006)。这种炎症反应伴随着LTL最高三分位数组中髓系细胞增加,主要是循环中性粒细胞增多(P = 0.0025)和单核细胞增多(P = 0.01)。多变量分析显示LTL(风险比2.6,95%置信区间1.4 - 5.1,P = 0.004)和PCT水平(风险比4.3,95%置信区间1.7 - 11.0,P = 0.003)是死亡率的独立预测因素。
TAVR后LTL较长与死亡率增加相关。这可能是由于细胞增殖能力增强导致髓系和全身炎症所致。我们的研究结果表明,针对特定炎症途径可能是提高某些退行性主动脉瓣狭窄患者生存率的一种新策略。