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Updated: May 12, 2026

Ultrasonic Assessment of Myocardial Microstructure
Published on: January 14, 2014
Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement
Bo Eric Beuthner1,2, Manar Elkenani1,2, Katja Evert3
1Department of Cardiology and Pneumology, University Medical Centre Göttingen, Georg August University of Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany.
Insights
The co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA) is lower than expected at 4.9%. A new algorithm can help screen for CA in AS patients, improving early detection and outcomes.
Area of Science:
- Cardiology
- Pathology
- Biomarker Discovery
Background:
- Co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA) varies significantly in existing literature.
- Transcatheter aortic valve replacement (TAVR) provides an opportunity to study this co-prevalence.
- Histological analysis is crucial for accurate diagnosis of co-existing conditions.
Purpose of the Study:
- To determine the histological co-prevalence of AS and CA in patients undergoing TAVR.
- To develop a predictive algorithm for identifying AS patients with concomitant CA.
- To investigate clinical and proteomic differences between patients with AS alone and those with both AS and CA.
Main Methods:
- Prospective, monocentric study analyzing endomyocardial biopsies from 162 TAVR patients.
- Histological examination using H&E, EVG, and Congo red staining.
- Analysis of clinical parameters, serum biomarkers (proteomics), and development of a screening algorithm.
Main Results:
- The co-prevalence of AS and CA was found to be 4.9%.
- Patients with concomitant CA exhibited higher NT-proBNP, lower voltage-to-mass ratio, and lower transaortic gradients.
- Concomitant CA was associated with increased risk of post-procedural acute kidney injury and sudden cardiac death (SCD).
- A proposed algorithm using clinical parameters achieved 66.6% sensitivity and 98.1% specificity for CA screening in AS patients.
Conclusions:
- The actual co-prevalence of AS and CA is lower than previously suggested.
- AS patients with concomitant CA have a higher risk of SCD, despite good overall 1-year survival.
- A novel multimodal algorithm can effectively screen for CA in AS patients using routine clinical data.
- Proteomic biomarkers show potential for future diagnostic improvements.
Aims:
Studies have reported a strongly varying co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co-prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co-prevalence of AS and CA.
Methods And Results:
In this prospective, monocentric study, endomyocardial biopsies of 162 patients undergoing TAVR between January 2017 and March 2021 at the University Medical Centre Göttingen were analysed by one pathologist blinded to clinical data using haematoxylin-eosin staining, Elastica van Gieson staining, and Congo red staining of endomyocardial biopsies. CA was identified in only eight patients (4.9%). CA patients had significantly higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (4356.20 vs. 1938.00 ng/L, P = 0.034), a lower voltage-to-mass ratio (0.73 vs. 1.46 × 10-2 mVm2/g, P = 0.022), and lower transaortic gradients (Pmean 17.5 vs. 38.0 mmHg, P = 0.004) than AS patients. Concomitant CA was associated with a higher prevalence of post-procedural acute kidney injury (50.0% vs. 13.1%, P = 0.018) and sudden cardiac death [SCD; P (log-rank test) = 0.017]. Following propensity score matching, 184 proteins were analysed to identify serum biomarkers of concomitant CA. CA patients expressed lower levels of chymotrypsin (P = 0.018) and carboxypeptidase 1 (P = 0.027). We propose an algorithm using commonly documented parameters-stroke volume index, ejection fraction, NT-proBNP levels, posterior wall thickness, and QRS voltage-to-mass ratio-to screen for CA in AS patients, reaching a sensitivity of 66.6% with a specificity of 98.1%.
Conclusions:
The co-prevalence of AS and CA was lower than expected, at 4.9%. Despite excellent 1 year mortality, AS + CA patients died significantly more often from SCD. We propose a multimodal algorithm to facilitate more effective screening for CA containing parameters commonly documented during clinical routine. Proteomic biomarkers may yield additional information in the future.

