Abstract

Background

Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt.

Methods

Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (^99mTc-hydroxymethylene diphosphonate – ^99mTc-HMDP), innervation (¹²³I-metaiodobenzylguanidine – ¹²³I-MIBG), and perfusion (^99mTc-tetrofosmin).

Results

Median summed ^99mTc-HMDP score was 60 (58–62), denoting a severe and diffuse amyloid burden. Planar ¹²³I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3–1.6], range 1.2–1.9, reference value ≥2.0). Summed ¹²³I-MIBG score was 12 (6–22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5–11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative ^99mTc-HMDP uptake) and innervation (as relative ¹²³I-MIBG uptake) did not achieve statistical significance at both segmental (p = .252) and regional level (p = .251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and ¹²³I-MIBG scores increased with ^99mTc-HMDP scores. Segments and regions with prominent hypoperfusion also showed a higher degree of denervation (r = 0.500 and 0.591, respectively; both p < .001).

Conclusions

Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.

中文翻译：

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野生型转甲状腺素蛋白淀粉样变性中的心脏交感神经去神经支配。

摘要

背景

由于TTR基因突变（变异淀粉样蛋白 TTR 淀粉样变性，ATTRv）或与年龄相关的现象（野生型 ATTR，ATTRwt），可能会发生错误折叠的甲状腺素蛋白 (TTR) 的组织积累。在 ATTRv 中已经报道了心脏交感神经去神经支配，但从未在 ATTRwt 中进行过研究。

方法

连续 15 名 ATTRwt 心肌病患者（81% 男性，中位年龄 82 岁，无既往心肌梗塞史）接受碲化镉锌断层成像检查淀粉样蛋白负荷（^99m Tc-羟基亚甲基二膦酸酯 - ^99m Tc-HMDP），神经支配（¹²³ I-间碘苄基胍– ¹²³ I-MIBG ）和灌注（^99m Tc-tetrofosmin）。

结果

^99m Tc-HMDP 总分中位数为 60 (58-62)，表明存在严重且弥散的淀粉样蛋白负担。平面¹²³ I-MIBG 检查显示早期和晚期 H/M 比值降低（晚期 H/M 比值：1.5 [1.3-1.6]，范围 1.2-1.9，参考值≥2.0）。求和¹²³ I-MIBG得分为12（6-22）中，用在infero隔最突出去神经支配，下侧和infero -外侧区域; 总静息评分为 7 (5-11)，下中隔和下中隔区域的心肌灌注程度最低。淀粉样蛋白负荷（相对^99m Tc-HMDP 摄取）和神经支配（相对¹²³ I-MIBG 摄取）之间的相关性在两个节段（p = .252) 和区域水平 ( p  = .251)。然而，去神经支配倾向于与淀粉样蛋白负荷同时恶化，并且¹²³ I-MIBG 评分随着^99m Tc-HMDP 评分的增加而增加。显着低灌注的节段和区域也显示出更高程度的去神经支配（ 分别为r = 0.500 和 0.591；两者p  < .001）。

结论

ATTRwt 心肌病患者表现出心脏交感神经去神经支配，特别是在下壁和间隔心肌壁。心肌低灌注具有相似的区域模式，而淀粉样蛋白负荷更广泛。