AS-amyloidosis. Dual pathology or novel disease? A multimodality, multi-centre assessment across health and disease
Authors: Patel K , Scully P , Nitsche C , Williams S , Tillin T , Captur G , Chako L , Newton J , Kennon S , Menezes L , Pugliese F , Fontana M , Treibel TA , Mascherbauer J , Moon JC 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

onbehalf
AS-Amyloidosis consortium

Background
The coexistence of severe aortic stenosis (lone AS) and transthyretin cardiac amyloidosis (lone amyloidosis) is common, but the resultant AS-amyloidosis phenotype is unclear.

Purpose
We characterised AS-amyloidosis, hypothesizing that the dual insult of AS-amyloidosis results is a severe phenotype.

Methods
We compared four cohorts with deep phenotyping: 81 older age controls, 359 lone AS, 36 AS-amyloidosis (Perugini grade 2 and 3) and 107 lone amyloidosis (Perugini grade 2 and 3).

Results
AS-amyloidosis was similar to lone AS with respect to left ventricular mass and LVEF (57 (45, 64)%). It was similar to lone amyloidosis with respect to lateral S" (0.04 (0.03, 0.06) m/s), NT-proBNP (4149 (1449, 6459) ng/L) and troponin T (56 (34, 100) ng/L). Whilst, prevalence of carpal tunnel syndrome (CTS) (17%) and diastolic function (E/A ratio 1.1 (0.8, 2.8)) were intermediate.

Conclusion
AS-amyloidosis is not a double insult from AS and amyloidosis, but a mixed phenotype with features similar to lone amyloidosis (cardiac biomarkers), lone AS (remodelling and LVEF) or intermediate (diastology and CTS).
Characteristics across all 4 groups Variable Older age controls (n = 81) Lone AS (n = 359) AS-amyloidosis (n = 36) Lone amyloidosis (n = 107) P value Age (years) 82 (80, 84)*†‡ 85 (80, 88)§∞ 88 (85, 92)# 80 (75, 84) &lt;0.005 Sex (% male) 69 *‡ 49 ∞ 61 # 94 &lt;0.005 Carpal tunnel syndrome (%) 0 2 § 17 # 38 &lt;0.005 Voltage/mass ratio 0.22 (0.14, 0.27)‡ 0.18 (0.13, 0.28)∞ 0.18 (0.09, 0.21)# 0.07 (0.05, 0.10) &lt;0.005 NT-ProBNP (ng/L) 131 (66, 221)*†‡ 1629 (639, 3941)§∞ 4149 (1449, 6459) 2888 (1755, 5483) &lt;0.005 hsTnT (ng/L) 12 (8, 17)*†‡ 24 (15, 40)§∞ 56 (34, 100) 62 (41, 82) &lt;0.005 Inferolateral wall thickness (cm) 0.9 (0.8, 1.0)*†‡ 1.1 (0.9, 1.3)∞ 1.3 (1.1, 1.5)# 1.7 (1.6, 1.9) &lt;0.005 Anteroseptal wall thickness (cm) 1.0 (0.9, 1.2)*†‡ 1.4 (1.2, 1.6)§∞ 1.5 (1.3, 1.8) 1.7 (1.6, 1.9) &lt;0.005 Indexed LV mass (g/m2) 79 (66, 102)*†‡ 128 (99, 152)∞ 126 (116, 140)# 174 (159, 200) &lt;0.005 LVEF (%) 59 (54, 63)‡ 59 (50, 65)∞ 57 (45, 64)# 39 (31, 48) &lt;0.005 Lateral S" (m/s) 0.08 (0.07, 0.09)*†‡ 0.07 (0.05, 0.08)§∞ 0.05 (0.04, 0.07) 0.05 (0.04, 0.06) &lt;0.005 Septal S" (m/s) 0.06 (0.06, 0.08)*†‡ 0.05 (0.04, 0.06)∞ 0.04 (0.03, 0.06) 0.04 (0.03, 0.05) &lt;0.005 E/A 0.7 (0.6, 0.8)*†‡ 0.8 (0.7, 1.3)§∞ 1.1 (0.8, 2.8)# 2.4 (1.8, 3.3) &lt;0.005 RV Wall thickness (cm) 0.4 (0.3, 0.4)*†‡ 0.4 (0.4, 0.6)∞ 0.6 (0.4, 0.7)# 0.8 (0.7, 1.0) &lt;0.005 TAPSE (cm) 2.4 (2.0, 2.7)*†‡ 2.1 (1.6, 2.5)∞ 1.9 (1.5, 2.1)# 1.4 (1.2, 1.9) &lt;0.005 Classical LFLG AS (%) 9 13 0.472 * p &lt; 0.05, Old age control vs Lone AS † p &lt; 0.05, Old age control vs AS-amyloidosis ‡ p &lt; 0.05, Old age control vs Lone amyloidosis § p &lt; 0.05, Lone AS vs AS-amyloidosis ∞ p &lt; 0.05, Lone AS vs Lone amyloidosis # p &lt; 0.05, AS-amyloidosis vs Lone amyloidosis Abstract Figure. AS-amyloidosis compared to other cohorts