Mechanism of Decompensation Evaluation - Aortic Stenosis (MODE-AS)

Mechanism of Left Ventricular Decompensation Evaluation - Aortic Stenosis

Aortic stenosis is the most common heart valve disease requiring intervention in high income countries. It is characterised by progressive valvular thickening, and restriction as well is hypertrophy and fibrosis of the left ventricle in response to pressure overload. The pathological processes in the left ventricle that ultimately result in heart failure and death are incompletely understood. Further elucidation of these processes and how they correlate with novel blood biomarkers may help us design new treatments and optimise the timing of surgical intervention.

In brief, recruited patients with severe aortic stenosis and scheduled to undergo valve replacement surgery will be invited for some simple tests (blood sampling, ECG, echocardiogram). A septal myocardial biopsy will be taken at the time of surgery and the disease valve retained. These will be examined histologically and pathological changes compared with results obtained from ECG, echocardiogram and blood tests.

Study Overview

• Status: Unknown
• Conditions: Myocardial Fibrosis; Aortic Stenosis; Left Ventricular Hypertrophy

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Russell J Everett, MBBS; Phone Number: 01312426361; Email: russell.everett@ed.ac.uk

Study Locations

• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH164SB
      • Recruiting
      • University of Edinburgh / NHS Lothian
      • Contact: Russell J Everett, MBBS; Phone Number: 01312426361; Email: russell.everett@ed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients referred for surgery for aortic valve disease (aortic stenosis group) and those referred for non-aortic valve cardiac surgery or elective ascending aorta surgery (control group)

Description

• Inclusion Criteria (aortic stenosis group):
• Age over 18
• Severe aortic stenosis with planned aortic valve replacement

Inclusion Criteria (control group):

• Age over 18
• Planned non-aortic valve cardiac or elective ascending aorta surgery

Exclusion Criteria (aortic stenosis group):

• Coexistent severe aortic or mitral regurgitation
• Coexistent mitral stenosis greater than mild in severity
• Acute valvular heart disease (e.g. acute mitral regurgitation or endocarditis)
• Acute pulmonary oedema or cardiogenic shock
• Coexistent hypertrophic cardiomyopathy
• Unable to give informed consent

Exclusion Criteria (control group):

• Significant aortic valve disease (mild aortic stenosis / regurgitation or greater)
• Acute valvular heart disease (e.g. acute mitral regurgitation or endocarditis)
• Acute pulmonary oedema or cardiogenic shock
• Coexistent hypertrophic cardiomyopathy
• Unable to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Severe aortic stenosis; Patients with severe aortic stenosis who are scheduled to undergo aortic valve replacement surgery
Control group; Patients scheduled to undergo non-aortic valve cardiac or elective ascending aortic surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of blood biomarkers with pathological changes on myocardial biopsy	Correlation between biomarkers (e.g. high sensitivity troponin I, BNP) with levels of myocardial fibrosis (collagen volume fraction as measured by picrosirius red staining)	Biomarkers collected within 1 month prior to date of surgery (and myocardial biopsy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of echocardiographic and ECG measures with pathological changes on myocardial biopsy	Correlation between imaging measures (e.g. LV diastolic function, longitudinal systolic function, ECG LVH criteria, ECG strain pattern) with levels of myocardial fibrosis (collagen volume fraction as measured by picrosirius red staining)	Biomarkers collected within 1 month prior to date of surgery (and myocardial biopsy)

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Investigators: Principal Investigator: Russell J Everett, MBBS, University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2017
• Primary Completion (Anticipated): November 15, 2021
• Study Completion (Anticipated): November 15, 2021

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 1, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Troponin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Cardiomegaly; Aortic Valve Stenosis; Hypertrophy; Constriction, Pathologic; Hypertrophy, Left Ventricular
• Other Study ID Numbers: E161633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No