Prevalence of amyloidosis among patients with mild to severe aortic stenosis. Validation of screening parameters
Authors: Voss F , Zweck E , Haschemi J , Spieker M , Angendohr S , Kelm M , Westenfeld R , Polzin A , Scheiber D 
Published: October 2024

Abstract

Background
Cardiac amyloidosis (CA) is an increasingly recognized cause of human heart failure. Up to 16% of patients with severe aortic stenosis (AS) undergoing transcatheter valve replacement have been reported to suffer concomitant transthyretin CA (ATTR). Since the diagnosis of CA implies distinct therapies with prognostic relevance, early diagnosis of CA is crucial. Different parameters have been described to improve screening accuracy for detection of CA, but it is unknown whether these parameters are valid, and the prevalence of CA is stable throughout the spectrum of AS.

Purpose
To validate screening parameters for the detection of CA in mild, moderate and severe AS.

Methods
Patient 65 years and above undergoing echocardiography with mild to severe AS, defined as calculated valve orifice area &lt;2 cm2 by velocity-time-integral, and an intraventricular septum thickness &gt; 11mm, fulfilling at least one of two additional criteria (Sokolow-Lyon-Index to left ventricular mass index ratio &lt; 1.5 or stroke volume index &lt; 35 ml/m2) were prospectively included and screened for CA using bone scintigraphy and immunofixation in blood and urine.

Results
57 patients were included and completed the diagnostic work-up. Mean age was 83 ± 0.7 years and 71% were male. Overall, 15 (26%) of patients were diagnosed with CA (12 with ATTR and 3 with light-chain CA, Figure1A). 17 patients had mild, 21 had moderate and 19 patients were diagnosed with severe AS. Among patients with mild AS 41% were diagnosed with CA, whereas only 24% of patients with moderate and 16% of patients with severe AS suffered CA (Figure 1B), these results did not show statistically significant differences (p= 0.2, by Chi-Square Quadrat test).
Patients with CA were less likely to have NYHA classes I or II (20 vs. 57%, p= 0.03), had higher values of NT-proBNP (4572 [2323; 6044] vs. 817 [589; 2571], p&lt; 0.001) and high-sensitive troponin (66 [47; 103.5] vs. 22.5 [17; 33.6], p&lt; 0.001) and were more likely to have an atrioventricular block of any degree (60 vs. 26%, p=0.04).

Conclusion
Prevalence of CA among patients fulfilling the criteria of this screening algorithm seems to be high independent of AS severity. Clinicians should not only focus on patients with severe AS to detect CA early. Further research is needed to estimate the prevalence of CA among all patients with AS.

Figure 1
A: Among patients with an age &gt;65 years, IVS &gt;11mm, AS and SLI/LVMMI &gt;1.5 or SVI &lt;35 ml/m2 26% (red area) of patients were diagnosed with CA (n= 57).
B: In patients with mild AS 41% were diagnosed with CA, whereas in patients with moderate AS only 24% and in patients with severe AS 16% had CA. These differences did not show statistical significance (p= 0.2).
IVS: intraventricular septum, AS: aortic stenosis, SLI: Skolow-Lyon-Index, LVMM= left ventricular myocardial mass index, SVI: stroke volume index, CA: cardiac-amyloidosis. (Statistics performed by chi-square test using GraphPad Prism 9.0).