Valvular Heart Disease

1347557 - Does Diabetes Lead to Distinct Alterations in Aortic Stenosis? Insights from Multiparametric CMR and Circulating Biomarkers

Thursday, January 26, 2023

1:00 PM – 2:00 PM

Location: Pacific Jewel

Presenting Author(s)

AD

Abhishek Dattani, MBBS

Clinical Research Fellow
University of Leicester, United Kingdom

Primary Author(s)

AD

Abhishek Dattani, MBBS

Clinical Research Fellow
University of Leicester, United Kingdom

Co-Author(s)

AA

Aseel Alfuhied, MSc

PhD Candidate
University of Leicester, United Kingdom
SA

Saadia Aslam

Clinical Research Fellow
University of Leicester, United Kingdom
Gaurav S. Gulsin, PhD

Academic clinical lecturer
University of Leicester
Leicester, England, United Kingdom
EB

Emer M. Brady, PhD

Post-doctoral research fellow
University of Leicester
Leicester, England, United Kingdom
MB

Marko Banovic, MD, PhD

Associate Professor
Clinical Centre of Serbia, Serbia
MJ

Michael Jerosch-Herold, PhD

Associate Professor
Harvard Medical School, United States
HX

Hui Xue, PhD

Director, Imaging AI Program
National Institutes of Health
Bethesda, Maryland, United States
PK

Peter Kellman, PhD

Senior Scientist
National Institutes of Health, Maryland, United States
LZ

Lei Zhao, MD, PhD

Senior Scientific Director
Bristol Myers Squibb, Beijing, United States
MC

Mary E. Cvijic

Senior Scientific Director
Bristol Myers Squibb, United States
PC

Philippe Costet, PhD

Translational Early Program Lead
Bristol Myers Squibb, United States
CS

Christopher D. Steadman, MD

Consultant Cardiologist
Poole Hospital NHS Foundation Trust, United Kingdom
LN

Leong L. Ng, MD

Professor
University of Leicester, United Kingdom
Anvesha Singh, PhD

Associate Professor and Honorary Consultant Cardiologist
University of Leicester
Leicester, England, United Kingdom
Gerry P. McCann, MD

NIHR research professor
University of Leicester
Leicester, England, United Kingdom

Disclosure(s):

Gerry P. McCann, MD: No financial relationships to disclose

Background: Coexisting type 2 diabetes (T2D) has a detrimental impact on outcomes in patients with severe aortic stenosis (AS). Whether T2D is associated with distinct alterations in myocardial remodelling, exercise capacity and circulating biomarkers in AS patients is not well understood.

Methods: Adults with isolated moderate-severe AS were prospectively phenotyped with echocardiography, cardiac magnetic resonance (CMR) imaging, including quantitative adenosine stress and rest perfusion, and cardiopulmonary exercise testing (CPET). Forty-nine cardiovascular plasma biomarkers were assessed on a subset of the participants using a multiplex assay. All image analyses were performed blinded to participant status. Comparison between patients with and without T2D, were adjusted for age, sex, ethnicity, body mass index (BMI), systolic blood pressure, estimated glomerular filtration rate (eGFR) and mean aortic valve pressure gradient using analysis of covariance.

Results: A total of 251 participants were included comprising 53 with T2D and 198 non-T2D who were well matched for age, sex, ethnicity, blood pressure, aortic valve velocity and pressure gradients (Table 1). T2D patients had higher BMI and more hyperlipidaemia, but lower eGFR and smaller indexed valve area compared to non-T2D. Echocardiography showed similar indices of diastolic function between groups (E/A and E/e’ ratios). Participants with T2D had reduced exercise capacity: evidenced with lower peak workload and peak VO2 despite similar peak respiratory exchange ratio. 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 and lower myocardial perfusion reserve (Table 1 and Figure 1). Plasma biomarkers analysis demonstrated that patients with T2D (n=31) had higher levels of the inflammatory marker growth differentiation factor-15 (GDF-15; Log10 mean difference 0.732 pg/mL, 95% CI 0.107-1.356, p=0.022) and renin (Log10 mean difference 0.400 pg/mL, 95% CI 0.127-0.673, P=0.004) than non-T2D (n=136). GDF-15 inversely correlated with longitudinal peak early diastolic strain rate in T2D: rs= -0.472, p=0.008 and non-T2D: rs= -0.219, p=0.012.

Conclusion: In patients with moderate to severe AS, T2D is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and lower perfusion reserve, and increased renin and GDF-15. These alterations may partly explain the poorer prognosis associated with diabetes in AS.