Abstract
Background Low gradient severe aortic stenosis (LGAS) accounts for up to 35% of severe aortic stenosis cases and is associated with unfavourable outcomes when compared to high gradient aortic stenosis (HGAS). Controversy and conflicting evidence exist regarding this disease entity, yet the contributing pathophysiology is poorly understood. There is a paucity of invasive data to help characterise this phenomenon of distinct remodelling - how do they respond to valve intervention and what makes them “high-risk”?Methods Patients with severe symptomatic AS and normal LVEF were dichotomised according to their mean aortic valve pressure gradient of less than or greater to 40mmHg. Patients listed for trans-catheter aortic valve implantation (TAVI) underwent 3T stress perfusion cardiac magnetic resonance imaging (CMR) pre-(within 24 hours) and post-(4-8 months) TAVI. Left ventricular (LV) mechanics and coronary flow and pressure parameters were measured during hyperaemia and rapid pacing, immediately before and after TAVI, using a conductance LV catheter and dual-pressure and Doppler sensor–tipped guidewire in the mid-left anterior descending coronary artery.
Results 24 patients were recruited resulting in 19 suitable datasets (LGAS N=9, HGAS N=10, equally matched for comorbidities and symptoms. LGAS was characterised by smaller indexed LV end diastolic volumes (p=0.010) and indexed LV mass (p=0.037). Stress global endocardium-epicardium gradient did not change following TAVI (0.94 [0.81,0.98] to 0.95 [0.80,1.0], p=0.694) whereas global myocardial perfusion reserve index improved following TAVI (2.1 [1.8,2.3] to 2.4 [2.3,2.8], p=0.029). There was a less significant gradient in LGAS patients (0.959±0.089 to 0.846±0.100, p=0.018) but a trend toward reduced MPRI in this group (1.88±0.32 vs 2.30±0.64, p=0.091). Pre-TAVI, baseline coronary data demonstrated lower coronary augmentation pressure (p=0.035) and augmentation index (AIx, p=0.028) in the LGAS group along with reduced time-averaged peak Doppler flow velocity (APV, p=0.022) and coronary velocity time integral (VTI, p=0.006). These patients also exhibited a shorter ejection time (p=0.022), proportionately larger forward compression wave areas and smaller backward expansion waves (BEW) during rest, hyperaemia and rapid pacing when compared to HGAS patients. They also demonstrated increased inhibitory forward expansion waves (p=0.021). Lower baseline end LV systolic pressure (p=0.004), inotropy (dP/dt+, p=0.031), lusitropy (dP/dt-, p=0.050), pressure volume area (p=0.020), and stroke work (p=0.019) were observed in the LGAS group along with reduced LV volumes during hyperaemia (p=0.040) and pacing (p=0.003). Pacing at 90bpm induced minimal response in the LGAS ventricles, but a more profound impact in HGAS ventricles on the delta change in end systolic volume (-12±45% vs +31±31%, p=0.048) and ejection fraction (-1±15% vs -19±12%, p=0.016). Post-TAVI, the hyperaemic BEW fell sharply (p<0.001) in both groups, along with coronary VTI (p=0.018) and APV (p=0.024), whilst coronary AP and AIx remained lower in LGAS patients (p=0.035 and p=0.028, respectively). The LGAS group displayed a less profound drop in dP/dt+ (-19±15% vs -37±9%, p=0.013) and dP/dt- (-17±19% vs -39±15%, p=0.015) at rest following intervention. Diastolic microvascular resistance was increased in LGAS patients during hyperaemia following TAVI (p=0.025). Repeat CMR demonstrated statistically significant reduction in indexed LV volume and mass (p=0.003 and p<0.001, respectively) with significant increase in 3D global peak radial, circumferential and longitudinal strain (p=0.006, p=0.010 and p=0.013, respectively). There was no difference in remodelling patterns or follow up perfusion assessment between cohorts.
Conclusion This is the first study detailing the combined invasive and CMR pathophysiological changes associated with LGAS. Despite invasive parameters indicating a disease of less severe AS, blunted microvascular-originating waves, and disproportionate myopathic and ischaemic changes in the LGAS group may underlie the adverse prognosis associated with this poorly understood condition.
| Date of Award | 1 Mar 2021 |
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| Original language | English |
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| Supervisor | Bernard D Prendergast (Supervisor) & Simon Redwood (Supervisor) |