Severe aortic stenosis is associated with left atrial prothrombotic flow changes that persists despite successful aortic valve replacement

Abstract Background Severe aortic stenosis (AS) is associated with ischaemic stroke independently of atrial fibrillation (AF) or other causes. Even after aortic valve replacement (AVR), patients remain affected by up to 15% five-year rate of incident ischaemic strokes independently of AVR-related complications and with knowledge gaps in the underlying pathophysiology. Purpose To assess whether severe AS leads to prothrombotic left atrial (LA) flow changes with reduction of LA velocities and vorticity which do not normalise after AVR. Methods Seventy-seven participants without history of AF were recruited in this study: N=40 with severe AS (60% male; age 73 ±10 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3) and N=37 controls with similar clinical risk profile (51% male; age 71 ±6 years, BMI 28 ±5 Kg/m2, median CHA2DS2VASc = 3). All participants underwent a cardiovascular magnetic resonance (CMR) scan to quantify left ventricular (LV) volumes, mass, and ejection fraction (LVEF), LV global longitudinal strain (GLS) as a sensitive marker of longitudinal dysfunction, LA maximum volume and emptying fraction (LAEF), LA blood flow peak velocity and vorticity by 4-dimensional flow CMR. Out of the 40 patients with severe AS, N=23 (58%) underwent a successful AVR and were followed-up with a repeat CMR scan at approximately 6 months after surgery. Results When compared to matched controls, patients with severe AS displayed significantly higher LV mass, smaller LA and LV volumes (i.e. concentric LV hypertrophy), significantly reduced GLS but higher (more hyperdynamic) LVEF (all p<0.05), as expected. LAEF (i.e. global LA function) was not significantly different from controls but despite this, severe AS was associated with slightly lower LA peak flow velocity (mean 0.25 vs. 0.28 m/sec respectively) and lower LA flow vorticity (mean 16.6 vs. 21.1 radians) compared to controls (both p<0.05). Successful AVR led to complete regression of LV hypertrophy (p<0.05) with LV mass that was no longer different from controls (p>0.05). Nevertheless, post-AVR patients displayed a persistent adverse morpho-functional phenotype characterised by persistently smaller LA and LV volumes, persistently hyperdynamic LV function with reduced GLS (all p<0.05), as well as adverse LA flow changes with significantly lower velocity (mean 0.24 vs 0.28 m/sec, p=0.003) and vorticity when compared to controls (17.1 vs 21.1 radians, p<0.001). Conclusions Patients with severe AS display adverse LA physiology and structure (prothrombotic LA flow characteristics in smaller LA size) and LV changes (smaller size with reduced longitudinal function and hyperdynamic function), which persist after successful AVR despite normalisation of the LV hypertrophy.Figure 1