Cardiac structural, functional remodelling, and perfusion impairments across the spectrum of aortic stenosis
Authors: Giannoudi M , Procter H , Kotha S , Jex N , Chowdhary A , Thirunavukarasu S , Plein S , Cubbon R , Xue H , Valkovic L , Kellman P , Dweck M , Greenwood J , Levelt E 
Published: October 2024

Abstract

Background
Aortic stenosis (AS) accounts for substantial global morbidity and premature mortality even in moderate AS (Mod-AS). Whilst myocardial remodeling response is considered critical in the adverse prognosis of Mod-AS, the precise mechanisms remain poorly understood. We aimed to prospectively assess myocardial remodeling, perfusion and energetics differences in Mod-AS and severe AS (Severe-AS).

Methods
Fifty-two Severe-AS and 25 Mod-AS patients and 18 demographically-matched controls underwent cardiovascular magnetic resonance and phosphorus-magnetic resonance spectroscopy to define left ventricular (LV) mass and function, global longitudinal shortening (GLS), rest and adenosine-stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR), layer-specific perfusion metrics (subendocardial [Endo], subepicardial [Epi] MBF and MPR, and Endo-Epi-MBF ratio [Endo/Epi]), myocardial scar on late gadolinium enhancement (LGE) imaging, and myocardial energetics (phosphocreatine:ATP ratio [PCr/ATP]).

Results
Compared to controls, with increasing AS severity, there was progressive increase in LV concentricity (LV mass-index (controls: 46[40,51],Mod-AS:58[51,65],Severe-AS: 70[65,75]g/m2; P&lt;0.0001), and stepwise decline in GLS (controls:19.9[17.6,22.2], Mod-AS:17.7[16.6,18.8], Severe-AS:13.4[12.5,14.4]%; P&lt;0.0001) with significant differences between Mod-AS and Severe-AS in all three comparisons. Both stress MBF(controls:2.1[1.9,2.3],Mod-AS:1.9[1.6,2.2],Severe-AS:1.3[1.2,1.5]ml/min/g; P&lt;0.0001) and MPR(controls:3.3[2.8,3.6],Mod-AS:2.8[2.4,3.2], Severe-AS:1.9[1.8,2.1]; P&lt;0.0001) were only significantly reduced in Severe-AS compared to controls, with significant differences also detected between Mod-AS and Severe-AS. However, stress-endo-MBF (controls:2.0[1.8,2.3], Mod-AS:1.7[1.5,2.0], Severe-AS:1.2[1.1,1.3]ml/min/g; P&lt;0.0001), stress-Endo/Epi(controls:1.00[0.93,1.07],Mod-AS:0.87[0.80,0.94],Severe-AS:0.81[0.75,0.82];P&lt;0.0001), rest-Endo/Epi (controls:1.12[1.10,1.14], Mod-AS:1.06[1.03,1.09], Severe-AS:1.03[1.02,1.06]; P&lt;0.0001) and endo-MPR (controls:3.2[2.7,3.6],Mod-AS:2.5[2.1,2.9],Severe-AS:1.7[1.5,1.8]; P&lt;0.0001) were all significantly reduced in both Mod-AS and Severe-AS. Compared to controls, both AS groups showed significantly lower PCr/ATP (controls:2.2[2.0,2.3],Mod-AS:1.8[1.6,2.0],Severe-AS:1.7[1.6,1.8]; P&lt;0.0001). Only the Severe-AS group had evidence of non-ischemic myocardial scarring on LGE (2.9[0.0,6.2]%), which was detected in 65%(n=34) of patients. AS severity (peak aortic valve velocity) correlated with stress-MBF (r=-0.45, P=0.0003), MPR (r=-0.44, P=0.0005) and GLS (r=-0.47, P=0.0001).

Conclusions
Moderate and severe-AS are both associated with cardiac concentric hypertrophy, reductions in myocardial energetics, and subendocardial hypoperfusion. Patients with Severe-AS exhibit a more pronounced phenotype with worse LV hypertrophy, contractile dysfunction and myocardial scarring compared to Mod-AS patients.