28 Impact of Diabetes on Cardiac Remodelling, Microvascular Dysfunction and Exercise Capacity in Aortic Stenosis

Introduction Untreated severe aortic stenosis (AS) has a poor prognosis. Coexisting type 2 diabetes (T2D) has a detrimental impact on progression and prognosis, but there is limited data on whether there are distinct alterations in myocardial remodelling and exercise capacity in AS patients with T2D. Materials and Methods In this pooled analysis of prospectively recruited participants from 3 studies conducted at a single centre, adults with moderate-severe aortic stenosis were phenotyped with echocardiography, adenosine stress perfusion cardiac magnetic resonance (CMR) imaging, including quantitative perfusion, and cardiopulmonary exercise testing (CPET). Key exclusion criteria were other severe valve disease, persistent arrhythmia and contraindications to CMR. Between group comparisons were adjusted for age, sex, ethnicity, body mass index (BMI), systolic blood pressure, estimated glomerular filtration rate (eGFR) and mean aortic valve pressure gradient. Results 251 participants were included: T2D (n=53, median age 70, male 77%, severe AS 85%) and non-T2D (n=198, median age 69 years, male 75%, severe AS 78%). Participants were well matched for age, sex, ethnicity, blood pressure, maximum aortic valve velocity and pressure gradients. T2D patients had higher BMI (30±5 vs. 28±4 kg/m2, p=0.003), but lower eGFR (71[59–87] vs. 81[66–96] mL/min/1.73m², p=0.016) and indexed valve area (0.49±0.17 vs. 0.54±0.14 cm2/m2, p=0.037) compared to non-T2D. Participants with T2D had reduced exercise capacity: lower peak workload (90±33 vs. 110±40 watts, p=0.002) and peak VO2 (14.9±4.9 vs. 17.4±5.2) despite similar peak respiratory exchange ratio. Echocardiography showed higher septal e’ in the T2D group (6.9±4.2 vs. 6.4±3.4 cm/s, p=0.046) but similar E/A and E/e’ ratios. On CMR, left ventricular volumes, mass, systolic function (ejection fraction and strain) and diastolic function (peak early diastolic strain rate) were similar as were left atrial volumes. Patients with T2D had higher extracellular volume (25.9±3.2 vs. 24.8±2.4%, p=0.027) and lower myocardial perfusion reserve (2.02±0.77 vs. 2.34±0.68, p=0.044). Conclusion In patients with moderate to severe AS, T2D is associated with more diffuse fibrosis, worse microvascular dysfunction and reduced exercise capacity. These adverse effects on cardiac remodelling may partly explain the poorer prognosis associated with diabetes in AS.