Risk-score performance for detecting transthyretin cardiac amyloidosis in severe aortic stenosis: a prospective cohort study
K Graczyk, E Dziewiecka, A Stepien-Wroniecka, M Winiarczyk, N Przytula, W Szot, K Holcman, M Kostkiewicz, P RubisAbstract
Introduction
The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and severe aortic stenosis (AS) presents diagnostic challenges. This study aimed to determine the prevalence and clinical characteristics of patients with combined ATTR-CA and severe AS, and to evaluate the role of existing models in refining the diagnostic process.
Methods
We conducted a prospective study on 104 consecutive patients with severe AS, defined as aortic valve area (AVA) <1cm2. Comprehensive evaluation included clinical and laboratory assessment, electrocardiography, transthoracic echocardiography, and planar whole-body bone scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) using technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) tracer. Patients were divided into two subgroups based on the presence or absence of ATTR. Additionally, we evaluated the following diagnostic models: the RAISE score and its modified variations, and the T-AMYLO simplified score and multivariable formula.
Results
Nineteen (18%) patients with severe AS also had ATTR-CA (ATTR-CA-AS). Compared with patients with severe AS alone, those with ATTR-CA-AS were significantly older (82.6±7.4 vs. 76±6.9, p<0.001), more often had arrhythmic and conduction disorders (atrial fibrillation, implanted pacemakers, and longer QRS duration), and had reduced left ventricular ejection fraction (44.6% vs. 54.7%, p=0.03). Patients with ATTR-CA-AS more frequently presented with the low-gradient/low-flow phenotype of AS (73.7%, p=0.009). Red flags were common in the ATTR-CA-AS group, including carpal tunnel syndrome [8 (42%) vs. 5 (6%), p<0.001] and lumbar canal stenosis [3 (16%) vs. 2 (2.3%), p=0.016]. Both, NT-proBNP and troponin levels were significantly higher in patients with ATTR-CA-AS [4174.0 (1767-10881) vs. 1238 (402.5-3419.75)pg/mL; p<0.001; and 59.6 vs. 23.3ng/L, p<0.001, respectively). After a 6-month follow-up, a similar number of deaths occurred in both groups; no surgical aortic valve replacement was performed in the ATTR-CA-AS population due to high operative risk (EuroSCORE II 5.5±3.8). The eRAISE model demonstrated the highest diagnostic accuracy (AUC 0.948). The T-AMYLO score (AUC 0.853, 95%CI 0.75-0.96) provided a distinct framework for risk stratification: <3 points, with a sensitivity of 89.5%, indicated a low probability of ATTR-CA, whereas ≥7 points indicated high risk, with a specificity of 98.7% for ATTR-CA.
Conclusions
The coexistence of ATTR-CA in patients with severe AS is common. Identification of key clinical and echocardiographic parameters may facilitate earlier diagnosis and improve patient management. Implementing risk scores in routine practice could enhance diagnostic accuracy for ATTR-CA in patients with AS stenosis, given their strong diagnostic performance and ease of assessment.ROC curves for the scoresFor image description, please refer to the figure legend and surrounding text.