Purpose

While early diagnosis is crucial, as new treatments can significantly slow the progression of the disease, there is growing evidence on the application of novel imaging techniques for detecting transthyretin amyloidosis (ATTR) in pre-symptomatic stages. This study aimed to evaluate the utility of pre-symptomatic scintigraphic imaging cascade screening for early detection of ATTR.

Methods

During the period from 2020 to 2024, we conducted a prospective study that enrolled 100 consecutive adults. The study utilized a multimodal cascade screening approach to assess asymptomatic relatives of individuals with ATTR (ClinicalTrials.gov Identifier: NCT05814380). The analysis incorporated clinical data, genetic testing, echocardiography, scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD, regardless of the predicted age of disease onset.

Results

Overall, scintigraphy identified cardiac amyloidosis (CA) in 8.2% of relatives, while 20.5% carried a pathogenic transthyretin variant without radiotracer uptake, with Phe53Leu being predominant. Notably, no relatives of wild-type ATTR patients exhibited CA on scintigraphy or carried a transthyretin variant. Additionally, newly-diagnosed relatives with ATTR CA presented elevated high-sensitivity troponin levels and exhibited a higher incidence of pathological electrocardiographic Q waves, greater thickness of the intraventricular septum and left ventricular posterior wall, a notable decline in lateral wall and intraventricular septal E' tissue velocities measured by TDI, and the "5–5-5" sign (p < 0.05).

Conclusion

The presented findings demonstrate that implementing a systematic screening protocol, which integrates genetic and scintigraphic testing, facilitates the early detection of ATTR. Crucially, a significant proportion of asymptomatic relatives of patients with hereditary ATTR may suffer from underlying CA.

Registration

ClinicalTrials.gov Identifier: NCT05814380.

中文翻译：

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心脏转甲状腺素蛋白淀粉样变性的症状前闪烁显像和遗传级联筛查

 目的

虽然早期诊断至关重要，因为新的治疗方法可以显着减缓疾病的进展，但越来越多的证据表明，在症状前阶段应用新的成像技术来检测转甲状腺素蛋白淀粉样变性 （ATTR）。本研究旨在评估症状前闪烁显像成像级联筛查对早期检测 ATTR 的效用。

 方法

在 2020 年至 2024 年期间，我们进行了一项前瞻性研究，连续招募了 100 名成年人。该研究采用多模式级联筛查方法来评估 ATTR （ClinicalTrials.gov 标识符： NCT05814380） 个体的无症状亲属。该分析结合了临床数据、基因检测、超声心动图、闪烁显像和单光子发射计算机断层扫描/计算机断层扫描 （SPECT/CT） 与 [99mTc]Tc-DPD，无论预测的发病年龄如何。

 结果

总体而言，闪烁显像在 8.2% 的亲属中发现了心脏淀粉样变性 （CA），而 20.5% 的亲属携带致病性转甲状腺素蛋白变体，没有放射性示踪剂摄取，其中 Phe53Leu 占主导地位。值得注意的是，野生型 ATTR 患者的亲属在闪烁显像上没有表现出 CA 或携带转甲状腺素蛋白变体。此外，新诊断的 ATTR CA 亲属表现出高敏肌钙蛋白水平升高，并表现出病理心电图 Q 波的发生率更高，脑室间隔和左心室后壁厚度增加，通过 TDI 测量的侧壁和脑室间隔 E' 组织速度显着下降，以及“5-5-5”征 （p < 0.05）。

 结论

提出的结果表明，实施整合遗传和闪烁显像检测的系统筛查方案有助于 ATTR 的早期检测。至关重要的是，遗传性 ATTR 患者的很大一部分无症状亲属可能患有潜在的 CA。

 注册

ClinicalTrials.gov 标识符：NCT05814380。