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. 2025 Sep 24;11(1):81.
doi: 10.1186/s40959-025-00383-w.

Evaluation of a screening algorithm to detect cardiac amyloidosis in mild to severe aortic valve stenosis

Fabian Voß  1 , Elric Zweck  2 , Jean Marc Haurand  2 , Jafer Haschemi  2 , Christian Jung  2 , Tobias Zeus  2 , Kathrin Klein  2 , Ralf Westenfeld  2   3 , Stephan Angendohr  2 , Roland Fenk  4 , Roman Pfister  5 , Maximilian Spieker  2 , Malte Kelm  2   6 , Amin Polzin #  2 , Daniel Scheiber #  2
Affiliations

Evaluation of a screening algorithm to detect cardiac amyloidosis in mild to severe aortic valve stenosis

Fabian Voß et al. Cardiooncology. .

Abstract

Background: Cardiac Amyloidosis (CA) remains highly underdiagnosed, especially among patients with causes of increased ventricular wall thickness, such as aortic stenosis (AS). The prevalence of CA throughout the spectrum of mild to severe AS is unknown and specific validated diagnostic parameters for this population are lacking. Here, we propose and prospectively evaluate a screening algorithm for CA among patients with mild to severe AS.

Methods: In this prospective, single-center study (NCT05010980), we included patients ≥ 65 years with mild to severe AS, an interventricular septum thickness > 11 mm, and at least one of the following criteria: Sokolow-Lyon-Index to left ventricular mass index ratio < 1.6 or stroke volume index < 35 ml/m2. Participants were prospectively screened for CA according to current guideline recommendations.

Results: After screening 2126 patients of whom 187 were eligible, 57 participants were enrolled and completed the diagnostic work-up. Mean age was 83 ± 0.7 years and 71% were male. 30% of the participants had mild, 37% had moderate and 33% had severe AS, respectively. Overall 26% of participants were diagnosed with CA. The prevalence of CA was higher among patients with mild AS (41%) compared to participants with moderate (24%) or severe AS (16%, p = 0.01). Within this preselected patient population, troponin (AUC:0.9, p < 0.0001) and NT-proBNP (AUC:0.86, p < 0.0001) further improved discrimination of patients with and without CA.

Conclusion: The prevalence of CA among AS patients fulfilling the preselected inclusion criteria was high, especially among those with mild to moderate AS. Implementing these criteria in clinical protocols could improve early diagnosis of CA.

Keywords: Aortic stenosis; Cardiac amyloidosis; Screening algorithm.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the ethics committee of the Medical Faculty of the Heinrich-Heine-University in Duesseldorf (reference number: 2021 − 1427). All studies were carried out in accordance with the declaration of Helsinki. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Inclusion criteria and screening algorithm. Patients ≥ 65 years with an IVS > 11 mm, AOA < 2cm2 and one additional criterium either SVI < 35 ml/m2 and/or SLI/LVMI < 1.6 mV/g/m2 were scheduled for bone-scintigraphy, immunofixation in serum and urine and serum free light chain assays. IVS: interventricular septum, AOA: aortic valve orifice area, SVI: stroke volume index, SLI: Sokolow-Lyon index, LVMI: leftventricular myocardial mass index; created in biorender.com
Fig. 2
Fig. 2
Frequency of Cardiac Amyloidosis using the predefined screening algorithm. A: Frequency of ATTR and AL CA among included patients and B: Prevalence of CA was associated with severity of aortic stenosis (G2 = 6.24, p = 0.01, AUC: 0.7, p = 0.02 by logistic regression). ATTR: transthyretin amyloidosis, AL: light-chain amyloidosis, CA: cardiac amyloidosis, AUC: area under the curve
See this image and copyright information in PMC

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