Pre-symptomatic scintigraphic and genetic cascade screening in cardiac transthyretin amyloidosis

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.

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.

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).

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.

ClinicalTrials.gov Identifier: NCT05814380.