Cardiac structural, functional remodelling, and perfusion impairments across the spectrum of aortic stenosis

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<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<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<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<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<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<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<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<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<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.