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. 2024 Jul 2;13(13):e034723.
doi: 10.1161/JAHA.124.034723. Epub 2024 Jun 21.

Prevalence, Characteristics, and Impact on Prognosis of Aortic Stenosis in Patients With Cardiac Amyloidosis

Mohamed-Salah Annabi  1   2   3 , Rasmus Carter-Storch  1   4 , Amira Zaroui  2   5 , Arnault Galat  2   5 , Silvia Oghina  2 , Mounira Kharoubi  2   5 , Mélanie Bezard  2   5 , Geneviève Derumeaux  3   6 , Pascale Fanen  2   5 , François Lemonnier  7   8 , Elsa Poullot  2   8   9 , Emmanuel Itti  2   5 , Romain Gallet  2   5 , Emmanuel Teiger  2   5 , Philippe Pibarot  1 , Thibaud Damy  2   5 , Marie-Annick Clavel  1
Affiliations

Prevalence, Characteristics, and Impact on Prognosis of Aortic Stenosis in Patients With Cardiac Amyloidosis

Mohamed-Salah Annabi et al. J Am Heart Assoc. .

Abstract

Background: Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA.

Methods and results: We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; P=0.19).

Conclusions: Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Keywords: aortic stenosis; cardiac amyloidosis; echocardiography; prognosis; transthyretin.

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Figures

Figure 1
Figure 1. Study flowchart.
Shows inclusion and exclusion of patients into the study. The study population comprised 976 patients with confirmed cardiac involvement of either ATTR or AL amyloidosis. Patients who were not confirmed with CA were used as hospital‐based controls for the comparison of AS prevalence. AA indicates serum amyloid amyloidosis; AL, immunoglobulin light‐chain; AS, aortic stenosis, ATTR wt/v, transthyretin amyloidosis wild‐type/hereditary variant type; and CA, cardiac amyloidosis.
Figure 2
Figure 2. Crude prevalence of aortic stenosis and of aortic sclerosis in the overall population and according to CA subtype.
Histogram showing the crude prevalence of aortic stenosis in the whole cohort and according to cardiac amyloidosis type. AL indicates immunoglobulin light‐chain amyloidosis; AS, aortic stenosis; ATTRwt/v, transthyretin wild‐type/hereditary variant amyloidosis. *Corrected P<0.05.
Figure 3
Figure 3. Age‐ and sex‐adjusted prevalence of AS according to CA subtype.
Forest plot of the standardized (age‐ and sex‐adjusted) rate ratios and 95% CIs, to compare the prevalence of significant (ie, moderate to severe) AS among the different CA subtypes with our hospital‐based controls and population‐based reference as previously reported by Nkomo et al. AL indicates immunoglobulin light‐chain amyloidosis; AS, aortic stenosis; ATTRwt/v, transthyretin wild‐type/hereditary variant amyloidosis; and CA, cardiac amyloidosis. *Corrected P<0.05.
Figure 4
Figure 4. AS severity and flow gradient patterns of severe AS in patients with cardiac amyloidosis.
A, Shows that ATTRwt patients had the highest proportion of severe AS compared with the other CA subtypes. B, Shows that only a small minority of patients with severe AS had a high gradient (ie, a mean gradient ≥40 mm Hg or peak velocity≥4 m/s) and a relative majority had either classical or paradoxical LFLG AS. AL indicates immunoglobulin light‐chain amyloidosis; AS, aortic stenosis; ATTRwt/v, transthyretin wild‐type/hereditary variant amyloidosis; LFLG, low flow/low gradient; and NFLG, normal flow/low gradient. *Corrected P<0.05.
Figure 5
Figure 5. Prognostic impact of AS in patients with ATTRwt cardiac amyloidosis.
Kaplan–Meier survival curve for all‐cause death of patients with ATTRwt with moderate or greater AS (red line) compared with patients with ATTRwt with no or mild AS (blue line). AS indicates aortic stenosis; ATTRwt, wild‐type transthyretin amyloidosis; and HR, hazard ratio.
See this image and copyright information in PMC

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