Department of Cardiology and Pneumology, University Medical Centre Göttingen, Georg August University of Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany.
German Centre for Cardiovascular Research (DZHK), partner site Göttingen, Göttingen, Germany.
ESC Heart Fail. 2024 Jun;11(3):1636-1646. doi: 10.1002/ehf2.14709. Epub 2024 Feb 26.
Studies have reported a strongly varying co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co-prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co-prevalence of AS and CA.
In this prospective, monocentric study, endomyocardial biopsies of 162 patients undergoing TAVR between January 2017 and March 2021 at the University Medical Centre Göttingen were analysed by one pathologist blinded to clinical data using haematoxylin-eosin staining, Elastica van Gieson staining, and Congo red staining of endomyocardial biopsies. CA was identified in only eight patients (4.9%). CA patients had significantly higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (4356.20 vs. 1938.00 ng/L, P = 0.034), a lower voltage-to-mass ratio (0.73 vs. 1.46 × 10 mVm/g, P = 0.022), and lower transaortic gradients (Pmean 17.5 vs. 38.0 mmHg, P = 0.004) than AS patients. Concomitant CA was associated with a higher prevalence of post-procedural acute kidney injury (50.0% vs. 13.1%, P = 0.018) and sudden cardiac death [SCD; P (log-rank test) = 0.017]. Following propensity score matching, 184 proteins were analysed to identify serum biomarkers of concomitant CA. CA patients expressed lower levels of chymotrypsin (P = 0.018) and carboxypeptidase 1 (P = 0.027). We propose an algorithm using commonly documented parameters-stroke volume index, ejection fraction, NT-proBNP levels, posterior wall thickness, and QRS voltage-to-mass ratio-to screen for CA in AS patients, reaching a sensitivity of 66.6% with a specificity of 98.1%.
The co-prevalence of AS and CA was lower than expected, at 4.9%. Despite excellent 1 year mortality, AS + CA patients died significantly more often from SCD. We propose a multimodal algorithm to facilitate more effective screening for CA containing parameters commonly documented during clinical routine. Proteomic biomarkers may yield additional information in the future.
已有研究报道，主动脉瓣狭窄（AS）和心脏淀粉样变性（CA）的共同患病率存在较大差异。本研究旨在通过组织学方法确定行经导管主动脉瓣置换术（TAVR）患者中 AS 和 CA 的共同患病率，并制定一种算法来识别可能存在 AS 和 CA 共同患病的病例。
本前瞻性单中心研究纳入了 2017 年 1 月至 2021 年 3 月在哥廷根大学医学中心接受 TAVR 的 162 例患者，由一名病理学家对其进行分析，分析过程中盲法处理临床数据，使用苏木精-伊红染色、弹力纤维 Van Gieson 染色和刚果红染色对心肌活检组织进行分析。仅在 8 例患者（4.9%）中发现 CA。CA 患者的 N 端脑利钠肽前体（NT-proBNP）水平显著更高（4356.20 比 1938.00 ng/L，P=0.034），电压-质量比更低（0.73 比 1.46×10 mVm/g，P=0.022），跨主动脉压力梯度更低（平均 Pmean 17.5 比 38.0 mmHg，P=0.004）。与 AS 患者相比，并发 CA 患者术后急性肾损伤（50.0%比 13.1%，P=0.018）和心源性猝死（SCD；P（log-rank 检验）=0.017）的发生率更高。经过倾向评分匹配后，对 184 种蛋白进行分析以确定并发 CA 的血清生物标志物。CA 患者的糜蛋白酶（P=0.018）和羧肽酶 1（P=0.027）水平较低。我们提出了一种使用常用参数（每搏输出量指数、射血分数、NT-proBNP 水平、后壁厚度和 QRS 电压-质量比）的算法来筛查 AS 患者中的 CA，该算法的灵敏度为 66.6%，特异性为 98.1%。
AS 和 CA 的共同患病率低于预期，为 4.9%。尽管 1 年死亡率良好，但 AS+CA 患者的 SCD 死亡率明显更高。我们提出了一种多模态算法，以便更有效地筛选包含临床常规记录的参数的 CA。蛋白质组学生物标志物可能在未来提供更多信息。
