Biomarkers in Aortic Stenosis - B.A.S.S. (BASS)

Biomarkers in Aortic Stenosis, Hypertrophic Cardiomyopathy, Mitral Regurgitation, Aortic Regurgitation, Prosthetic Heart Valve Dysfunction, and Tricuspid Regurgitation From Pacemaker Leads Study

This study is being done to determine whether or not new blood test(s) can determine the severity of heart conditions. Aortic stenosis, hypertrophic cardiomyopathy, mitral regurgitation, aortic regurgitation, artificial heart valve regurgitation or stenosis, and tricuspid valve regurgitation associated with pacemaker leads are the cardiac disorders under study. The blood tests involve analysis for von Willebrand Factor antigen and activity, von Willebrand Factor multimers, and brain natriuretic peptide (BNP) levels. The results of the blood tests will be compared to the information from the clinically-indicated echocardiogram and one blood test compared to another.

Study Overview

• Status: Completed
• Conditions: Aortic Stenosis; Mitral Valve Insufficiency; Aortic Valve Insufficiency; Hypertrophic Cardiomyopathy; Tricuspid Valve Insufficiency; Disorder of Prosthetic Cardiac Valve
• Intervention / Treatment: Procedure: Blood Draw

Detailed Description

Patients with aortic stenosis, hypertrophic cardiomyopathy, mitral regurgitation, aortic regurgitation, artificial heart valve regurgitation or stenosis, and tricuspid valve regurgitation associated with pacemaker leads who are referred for clinically-indicated echocardiographic exams at Mayo Clinic, in Jacksonville, Florida will be screened for participation in the study. The plan is to have 292 people take part in this study. This minimal risk study will consist of the recording of patient data, activity and bleeding questionnaires, and collection and analysis of blood samples. Each blood sample will be analyzed for von Willebrand Factor antigen and activity, and von Willebrand Factor multimers, and BNP. Blood samples will be sent to the Mayo Special Coagulation Lab for analysis.

Objective:

This study seeks to assess the degree of association of the von Willebrand Factor activity indices and BNP to the severity of cardiac lesions, and to note a relationship between acquired bleeding the the hematologic abnormalities. Plasma will be stored in attempt to develop new in vitro tests of von Willebrand factor (VWF) activity.

• Study Type: Observational
• Enrollment (Actual): 378

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cardiology, referred for clinically-indicated echocardiograms

Description

Inclusion Criteria:

• patients with mild, moderate, or severe aortic stenosis or aortic or mitral prosthesis. Patients with aortic or mitral regurgitation. patients with hypertrophic cardiomyopathy. Patients with dysfunctional heart valve replacement or repair. Patients with severe tricuspid regurgitation associated with pacemaker or defibrillator lead. Ten normal control patients who will not be required to have echocardiography
• referred for a clinically indicated echocardiogram; the echo must be of good quality and specifically have patient height, weight, left ventricular outflow tract diameter, subaortic velocity profile by Doppler, and aortic transvalvular continuous wave Doppler velocity profile. For mitral regurgitation and aortic regurgitation the data must be adequate to allow calculation of regurgitant volume. For hypertrophic cardiomyopathy, a recording of left ventricular outflow tract peak velocity must be recorded
• 21 years or older
• patients with aortic stenosis, defined as peak aortic velocity greater than 2.5 m/sec with evidence of aortic valve thickening, or an aortic or mitral valve prosthesis
• able to provide written informed consent

Exclusion Criteria:

• Missing or inadequate echocardiographic data
• inability to give informed consent
• inability to provide a research blood sample
• hemoglobin less than 8
• severe valvular regurgitation
• stenosis of the mitral valve

Study Plan

How is the study designed?

Number of groups / cohorts

11

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aortic Stenosis; Restricted aortic valve motion and a peak Doppler aortic velocity > 2.5 m/sec blood draw	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Aortic regurgitation; Echocardiographic and Doppler evaluation revealing aortic regurgitation with data adequate to calculate regurgitant volume	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Aortic valve replacement; Mechanical or biological aortic valve replacement	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Mitral regurgitation; Echocardiographic and Doppler evaluation revealing mitral regurgitation with data adequate to calculate regurgitant volume	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Mitral valve replacement; Mechanical or biological mitral valve replacement	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Hypertrophic cardiomyopathy; Patients with known hypertrophic cardiomyopathy who are referred for clinically indicated echocardiography	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Severe TR with pacemaker / ICD lead; Patients referred for clinically indicated echocardiography who have severe tricuspid regurgitation associated with a pacemaker or defibrillator lead documented by echocardiography	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Prosthetic valve dysfunction; Patients with prior heart valve replacement or repair referred for clinically indicated echocardiography who demonstrate stenosis, regurgitation, dehiscence.	Procedure: Blood Draw; Two tubes of blood (about five tablespoons) will be drawn for research purposes, and these will be analyzed for the following tests: BNP (Brain Natriuretic Peptide); (PFA) Platelet Function Analyzer 100; von Willebrand Factor (vWF) antigen; (vWF) multimers; (vWF) *activity by latex aggregation; Plasma stored for development of new testing approaches
Normal controls; Patients with no heart murmur or history of valve replacement, stenosis, regurgitation, or hypertrophic cardiomyopathy
Left ventricular assist device patients; Patients with previously implanted LVAD
Renal dialysis patients; Patients on hemodialysis, peritoneal dialysis, or chronic kidney disease with dialysis fistula to be created.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Von Willebrand Multimer ratio to cardiac lesion severity	To accomplish the specific aims, the investigators propose to collect clinical and echocardiographic data, and blood samples for von Willebrand Factor antigen and activity, von Willebrand Factor multimers, and BNP in patients with aortic stenosis, or aortic or mitral valve prosthesis, mitral regurgitation, hypertrophic cardiomyopathy, aortic regurgitation, and tricuspid regurgitation associated with pacemaker or defibrillator.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of other VWF activity measures with cardiac lesion severity.	Comprehensively analyze the ability of VWF indices to discriminate severe from non-severe valvular disease, prosthetic valve dysfunction, and describe the prevalence of VWF abnormalities in this wide range of cardiac lesions associated with intravascular turbulence.	2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Joseph L Blackshear, M.D., Mayo Clinic

Publications and helpful links

General Publications

• Blackshear JL, Stark ME, Agnew RC, Moussa ID, Safford RE, Shapiro BP, Waldo OA, Chen D. Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome. J Thromb Haemost. 2015 Feb;13(2):191-6. doi: 10.1111/jth.12780. Epub 2014 Dec 12.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: April 12, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimate): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: aortic valve replacement; aortic stenosis; hypertrophic cardiomyopathy; mitral valve replacement; aortic valve regurgitation; mitral valve regurgitation; brain natriuretic peptide; von Willebrand factor; prosthetic valve dysfunction; tricuspid insufficiency
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Mitral Valve Insufficiency; Aortic Valve Insufficiency; Hypertrophy; Constriction, Pathologic; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Tricuspid Valve Insufficiency
• Other Study ID Numbers: 09-006757

Drug and device information, study documents

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