Supplementary Material for: Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis

Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3). Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

背景：目前尚不明确主动脉瓣（aortic valve, AV）处透析相关淀粉样变性（dialysis amyloid, DA）沉积与主动脉瓣狭窄（aortic stenosis, AS）之间的关联。
方法：本研究为横断面研究。连续纳入56例心脏手术标本与13例尸检标本，均来自透析时长中位数为8.8年的透析患者，由对临床数据设盲的专科认证病理学家对标本进行检测。若标本中的沉积物同时在偏振光下经刚果红染色呈苹果绿双折光，且被抗β2微球蛋白（anti-β2-microglobulin）抗体染色，则判定为存在透析相关淀粉样变性沉积。淀粉样沉积程度分级标准如下：(-) 无沉积物；(1+) 偶见小型沉积物；(2+) 多发小型至大型沉积物，或单发大型沉积物。钙化定义为标本中直径＞1mm的钙化沉积物。重度主动脉瓣狭窄（severe AS, sAS）定义为超声心动图检测显示平均跨瓣梯度＞50mmHg。本研究分析了透析相关淀粉样变性沉积的检出率，以及其与重度主动脉瓣狭窄之间的关联。
结果：71%的标本（n=49）检出透析相关淀粉样变性沉积，且沉积主要与钙化共存；仅1例标本检出非透析相关性淀粉样变性。剔除该非透析相关性淀粉样变性标本后，相较于“淀粉样沉积(-)且钙化≤1mm”组，“淀粉样沉积(1+)且钙化＞1mm”组与“淀粉样沉积(2+)且钙化＞1mm”组均与重度主动脉瓣狭窄相关，比值比（odds ratios, ORs）分别为13.5与34.2。在校正混杂因素后，仍可见“淀粉样沉积(2+)且钙化＞1mm”与重度主动脉瓣狭窄存在关联（OR=24.3）。
结论：透析患者主动脉瓣处的透析相关淀粉样变性沉积检出率较高；伴随钙化的透析相关淀粉样变性沉积可能参与主动脉瓣狭窄的病情加重过程。