Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
JACC Heart Fail. 2024 Jun;12(6):1073-1085. doi: 10.1016/j.jchf.2024.03.005.
Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration.
This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid beta 40 (Aβ40), and amyloid beta 42 (Aβ42) in a large, well-characterized cohort.
The study included 470 patients with HFrEF from a biobank-linked prospective registry at the Medical University of Vienna. High-sensitivity single-molecule assays were used for measurement. Unplanned heart failure (HF) hospitalization and all-cause death were recorded as outcome parameters.
All markers, but not the Aβ42:Aβ40 ratio, correlated with HF severity, ie, N-terminal pro-B-type natriuretic peptide and NYHA functional class, and comorbidity burden and were significantly associated with all-cause death and HF hospitalization (crude HR: all-cause death: NfL: 4.44 [95% CI: 3.02-6.53], t-tau: 5.04 [95% CI: 2.97-8.58], Aβ40: 3.90 [95% CI: 2.27-6.72], and Aβ42: 5.14 [95% CI: 2.84-9.32]; HF hospitalization: NfL: 2.48 [95% CI: 1.60-3.85], t-tau: 3.44 [95% CI: 1.95-6.04], Aβ40: 3.13 [95% CI: 1.84-5.34], and Aβ42: 3.48 [95% CI: 1.93-6.27]; P < 0.001 for all). These associations remained statistically significant after multivariate adjustment including N-terminal pro-B-type natriuretic peptide. The discriminatory accuracy of NfL in predicting all-cause mortality was comparable to the well-established risk marker N-terminal pro-B-type natriuretic peptide (C-index: 0.70 vs 0.72; P = 0.225), whereas the C-indices of t-tau, Aβ40, Aβ42, and the Aβ42:Aβ40 ratio were significantly lower (P < 0.05 for all).
Neurodegeneration is directly interwoven with the progression of HF. Biomarkers of neurodegeneration, particularly NfL, may help identify patients potentially profiting from a comprehensive neurological work-up. Further research is necessary to test whether early diagnosis or optimized HFrEF treatment can preserve cognitive function.
认知障碍在射血分数降低的心力衰竭（HFrEF）患者中很常见，影响自我护理和结局。新型血液生物标志物已成为神经退行性变的潜在诊断工具。
本研究旨在通过测量神经丝轻链（NfL）、总tau（t-tau）、β-淀粉样蛋白 40（Aβ40）和β-淀粉样蛋白 42（Aβ42）在一个大型、特征明确的队列中评估 HFrEF 中的神经退行性变。
该研究纳入了来自维也纳医科大学生物库相关前瞻性注册中心的 470 名 HFrEF 患者。使用高灵敏度单分子测定法进行测量。未计划的心力衰竭（HF）住院和全因死亡被记录为结局参数。
所有标志物（但 Aβ42:Aβ40 比值除外）均与 HF 严重程度相关，即 N 末端 B 型利钠肽前体和 NYHA 功能分级，以及合并症负担，并与全因死亡和 HF 住院显著相关（未校正 HR：全因死亡：NfL：4.44 [95%CI：3.02-6.53]，t-tau：5.04 [95%CI：2.97-8.58]，Aβ40：3.90 [95%CI：2.27-6.72]，Aβ42：5.14 [95%CI：2.84-9.32]；HF 住院：NfL：2.48 [95%CI：1.60-3.85]，t-tau：3.44 [95%CI：1.95-6.04]，Aβ40：3.13 [95%CI：1.84-5.34]，Aβ42：3.48 [95%CI：1.93-6.27]；P < 0.001）。在包括 N 末端 B 型利钠肽前体的多变量调整后，这些相关性仍然具有统计学意义。NfL 在预测全因死亡率方面的判别准确性与已确立的风险标志物 N 末端 B 型利钠肽前体相当（C 指数：0.70 与 0.72；P = 0.225），而 t-tau、Aβ40、Aβ42 和 Aβ42:Aβ40 比值的 C 指数显著降低（P < 0.05）。
神经退行性变与 HF 的进展直接交织在一起。神经退行性变的生物标志物，特别是 NfL，可能有助于识别可能从全面神经检查中获益的患者。需要进一步研究以测试早期诊断或优化 HFrEF 治疗是否可以保留认知功能。
