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Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System

Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System
Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System
Background: Type 2 diabetes mellitus (T2DM) has been established as an important independent risk factor for aortic stenosis. T2DM patients present with a higher degree of valve calcification and left ventricular dysfunction compared to patients without diabetes. This may be due to an increase in incidence and severity of myocardial fibrosis. Currently, there is no reliable method of determining the optimal timing of intervention for a patient with asymptomatic aortic stenosis or predicting when a patient will become symptomatic. Research into serum biomarkers to predict subclinical onset and track progression of aortic stenosis is hampered by the multimodal nature of the pathological processes ultimately responsible for aortic stenosis.

Objective: The aim of this study is to prove that an approach using a combination of serum biomarkers and the echocardiographic parameter global longitudinal strain (GLS) can be used to establish baseline status of fibrocalcific aortic valve disease, predict rate of progression, and quantitatively assess any regression of these processes following aortic valve replacement in patients with T2DM.

Methods: Validated serum biomarkers for the separate processes of calcification, inflammation, oxidative stress and fibrosis can be used to quantify onset and rate of progression of aortic stenosis. This, in combination with the echocardiographic parameter GLS, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, noninvasive one-stop assessment of aortic stenosis in patients with T2DM. The serum biomarkers BNP (B-type natriuretic peptide), Gal-3 (Galectin-3), GDF-15 (growth differentiation factor-15), sST2 (soluble suppression of tumorigenicity 2), OPG (osteoprotegerin), and microRNA 19b and 21 will be sampled from patients undergoing aortic valve replacement (with and without T2DM), patients with T2DM but without aortic valve disease and healthy volunteers. These patients will also undergo computed tomography (CT) scans for calcium scoring, magnetic resonance imaging (MRI) to quantify myocardial fibrosis, and myocardial strain imaging with speckle-tracking echocardiography. Samples of calcified native aortic valve and a biopsy of ventricular myocardium will be examined histologically to determine the quantity and distribution of calcification and fibrosis, and the secretome of these tissue samples will also be analyzed for levels of the same biomarkers as in the serum samples. All patients will be followed up with in 3 months and 12 months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis and CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment.

Results: Using all of the information gathered throughout the study will yield a ranking scale for use in the clinic, which will provide each patient with a fibrocalcific profile. This can then be used to recommend an optimal time for intervention.

Conclusion: A reliable, validated set of serum biomarkers combined with an inexpensive bedside echocardiographic examination can now form the basis of a one-stop outpatient-based assessment service, which will provide an accurate risk assessment in patients with aortic stenosis at first contact.
aortic stenosis, myocardial fibrosis, type 2 diabetes mellitus, biomarkers, ventricular remodelling, aortic valve replacement
8
Giritharan, Suresh
ffd59575-f0c8-458d-8222-c5997baee7ae
Cagampang, Felino
7cf57d52-4a65-4554-8306-ed65226bc50e
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Salhiyyah, Kareem
63ac0bb3-5b7d-4d9f-87e5-3a20ba738a6a
Duggan, Simon
509264ac-5d3d-47dd-acd8-433ecd0dd990
Ohri, Sunil K.
8aa5698c-78cf-4f59-a5af-5afa46f0348c
Giritharan, Suresh
ffd59575-f0c8-458d-8222-c5997baee7ae
Cagampang, Felino
7cf57d52-4a65-4554-8306-ed65226bc50e
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Salhiyyah, Kareem
63ac0bb3-5b7d-4d9f-87e5-3a20ba738a6a
Duggan, Simon
509264ac-5d3d-47dd-acd8-433ecd0dd990
Ohri, Sunil K.
8aa5698c-78cf-4f59-a5af-5afa46f0348c

Giritharan, Suresh, Cagampang, Felino, Torrens, Christopher, Salhiyyah, Kareem, Duggan, Simon and Ohri, Sunil K. (2019) Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System. JMIR Research Protocols, 8 (7), 8, [e13186]. (doi:10.2196/13186).

Record type: Article

Abstract

Background: Type 2 diabetes mellitus (T2DM) has been established as an important independent risk factor for aortic stenosis. T2DM patients present with a higher degree of valve calcification and left ventricular dysfunction compared to patients without diabetes. This may be due to an increase in incidence and severity of myocardial fibrosis. Currently, there is no reliable method of determining the optimal timing of intervention for a patient with asymptomatic aortic stenosis or predicting when a patient will become symptomatic. Research into serum biomarkers to predict subclinical onset and track progression of aortic stenosis is hampered by the multimodal nature of the pathological processes ultimately responsible for aortic stenosis.

Objective: The aim of this study is to prove that an approach using a combination of serum biomarkers and the echocardiographic parameter global longitudinal strain (GLS) can be used to establish baseline status of fibrocalcific aortic valve disease, predict rate of progression, and quantitatively assess any regression of these processes following aortic valve replacement in patients with T2DM.

Methods: Validated serum biomarkers for the separate processes of calcification, inflammation, oxidative stress and fibrosis can be used to quantify onset and rate of progression of aortic stenosis. This, in combination with the echocardiographic parameter GLS, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, noninvasive one-stop assessment of aortic stenosis in patients with T2DM. The serum biomarkers BNP (B-type natriuretic peptide), Gal-3 (Galectin-3), GDF-15 (growth differentiation factor-15), sST2 (soluble suppression of tumorigenicity 2), OPG (osteoprotegerin), and microRNA 19b and 21 will be sampled from patients undergoing aortic valve replacement (with and without T2DM), patients with T2DM but without aortic valve disease and healthy volunteers. These patients will also undergo computed tomography (CT) scans for calcium scoring, magnetic resonance imaging (MRI) to quantify myocardial fibrosis, and myocardial strain imaging with speckle-tracking echocardiography. Samples of calcified native aortic valve and a biopsy of ventricular myocardium will be examined histologically to determine the quantity and distribution of calcification and fibrosis, and the secretome of these tissue samples will also be analyzed for levels of the same biomarkers as in the serum samples. All patients will be followed up with in 3 months and 12 months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis and CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment.

Results: Using all of the information gathered throughout the study will yield a ranking scale for use in the clinic, which will provide each patient with a fibrocalcific profile. This can then be used to recommend an optimal time for intervention.

Conclusion: A reliable, validated set of serum biomarkers combined with an inexpensive bedside echocardiographic examination can now form the basis of a one-stop outpatient-based assessment service, which will provide an accurate risk assessment in patients with aortic stenosis at first contact.

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Accepted/In Press date: 23 May 2019
Published date: 12 August 2019
Keywords: aortic stenosis, myocardial fibrosis, type 2 diabetes mellitus, biomarkers, ventricular remodelling, aortic valve replacement

Identifiers

Local EPrints ID: 433010
URI: http://eprints.soton.ac.uk/id/eprint/433010
PURE UUID: 648b42be-d425-40fb-aae6-c3cf7ecd2a57
ORCID for Suresh Giritharan: ORCID iD orcid.org/0000-0002-5826-0812
ORCID for Felino Cagampang: ORCID iD orcid.org/0000-0003-4404-9853

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Date deposited: 06 Aug 2019 16:30
Last modified: 06 Jun 2024 02:03

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Author: Suresh Giritharan ORCID iD
Author: Christopher Torrens
Author: Kareem Salhiyyah
Author: Simon Duggan
Author: Sunil K. Ohri

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