Effect of Initiation With Sacubitril/valsartan on Blood Neurodegeneration Markers in HFrEF

IF 6.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiac Failure Pub Date : 2025-06-01 DOI:10.1016/j.cardfail.2025.01.021

SURIYA PRAUSMÜLLER MD , RAPHAEL WURM MD , MARKUS PONLEITNER MD , ELISABETH STÖGMANN MD , MARTIN HÜLSMANN MD , NOEMI PAVO MD, PhD

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引用次数: 0

Abstract

Background

Sacubitril/valsartan is a key therapy for heart failure with reduced ejection fraction (HFrEF). However, concerns remain regarding its potential impact on cognitive function, because neprilysin inhibition may influence amyloid-β (Aβ) metabolism. This study evaluates the effect of sacubitril/valsartan on plasma biomarkers of neurodegeneration.

Methods

Plasma neuromarkers (i.e., Aβ40, Aβ42, neurofilament light chain [NfL], and total tau [t-tau]) were measured at baseline, 3 months and 1 year after sacubitril/valsartan initiation by using the single-molecule array (SIMOA) technology in a cohort with HFrEF from a prospective registry with Biobank. Comparisons were made for baseline vs 3-month and baseline vs 1-year follow-up.

Results

A total of 31 patients with HFrEF (median age: 61 years, 74% male, median NT-proBNP level: 2333 pg/mL) were included. Aβ40 increased transiently at 3 months (228.6 pg/mL [Q1–Q3: 157.8–321.1] vs 138.8 [110.0–202.2]; P < 0.001) but remained unchanged at 1 year (215.0 [106.5–290.9]; P = 0.052). Aβ42 remained stable (9.90 [6.67–12.49] and 8.43 [5.57–11.86] vs 7.84 [6.50–11.02] pg/mL; P = 0.108 and 0.771), resulting in a reduced Aβ42/Aβ40 ratio at both follow-ups (0.039 [0.036–0.049] at 3 months, P < 0.001; 0.048 [0.041–0.060] at 1 year, P = 0.026; vs 0.055 [0.052–0.061]). Total tau remained unchanged (1.13 [0.91–1.90] and 1.21 [0.85–1.65] vs 1.03 [0.82–1.53] pg/mL; P = 0.068 and 0.188), while NfL increased at 1 year (28.3 [16.5–78.6] vs 22.6 [15.1–46.9] pg/mL; P = 0.013), with no short-term change (25.3 [15.0–51.3]; P = 0.502).

Conclusion

Sacubitril/valsartan therapy in patients with HFrEF leads to a transient increase in Aβ40 and a sustained reduction in the Aβ42/Aβ40 ratio. Stable t-tau and short-term stable NfL levels provide reassurance regarding the absence of immediate neuronal injury, while an NfL increase observed at 1 year may indicate ongoing progression of heart failure rather than direct neurotoxicity. These findings highlight the need for cautious interpretation of the Aβ42/Aβ40 ratio in neurocognitive assessments among patients treated with angiotensin receptor-neprilysin inhibitors. Further studies are warranted to clarify the long-term cognitive implications of sacubitril/valsartan in patients with HFrEF.

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开始使用苏比里尔/缬沙坦对HFrEF血液神经变性标志物的影响。

背景：沙克比利/缬沙坦是治疗心力衰竭伴射血分数降低（HFrEF）的关键药物。然而，由于neprilysin抑制可能影响淀粉样蛋白-β (Aβ)代谢，因此其对认知功能的潜在影响仍然值得关注。本研究评估了苏比里尔/缬沙坦对神经变性血浆生物标志物的影响。方法：采用单分子阵列（SIMOA）技术，在来自biobank前瞻性注册的HFrEF队列中，在基线、3个月和1年后，测量血浆神经标志物，即a β40、a β42、神经丝轻链（NfL）和总tau （t-tau）。对基线与3个月、基线与1年随访进行比较。结果：共纳入31例HFrEF患者（中位年龄：61岁，男性74%，NT-proBNP: 2333 pg/ml）。Aβ40在3个月时短暂升高[228.6 pg/ml (Q1-Q3: 157.8-321.1) vs. 138.8 pg/ml (110.0-202.2), p < 0.001]，但在1年后保持不变[215.0 (106.5-290.9),p = 0.052]。a - β42保持稳定[9.90（6.67-12.49）和8.43（5.57-11.86）比7.84 (6.50-11.02)pg/ml, p = 0.108和0.771]，导致a - β42/ a - β40比值降低[3个月时0.039 (0.036-0.049),p < 0.001；0.048 (0.041-0.060), p = 0.026 vs. 0.055(0.052-0.061)]。总tau蛋白保持不变[1.13（0.91-1.90）和1.21（0.85-1.65）比1.03 (0.82-1.53)pg/ml, p = 0.068和0.188]，而NfL在1年后增加[28.3（16.5-78.6）比22.6 (15.1-46.9)pg/ml, p = 0.013]，短期无变化[25.3 (15.0-51.3),p = 0.502]。结论：Sacubitril/缬沙坦治疗HFrEF患者可导致a - β40的短暂升高和a - β42/ a - β40比值的持续降低。稳定的t-tau和短期稳定的NfL水平可以保证没有立即的神经元损伤，而1年后观察到的NfL增加可能表明持续的心力衰竭进展，而不是直接的神经毒性。这些发现强调了在ARNi治疗患者的神经认知评估中对a - β42/ a - β40比值进行谨慎解释的必要性。需要进一步的研究来阐明sacubitril/缬沙坦对HFrEF的长期认知影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cardiac Failure 医学-心血管系统

CiteScore

7.80

自引率

8.30%

发文量

653

审稿时长

21 days

期刊介绍： Journal of Cardiac Failure publishes original, peer-reviewed communications of scientific excellence and review articles on clinical research, basic human studies, animal studies, and bench research with potential clinical applications to heart failure - pathogenesis, etiology, epidemiology, pathophysiological mechanisms, assessment, prevention, and treatment.