Biomarkers in Aortic Stenosis - B.A.S.S.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Aortic Stenosis, Disorder of Prosthetic Cardiac Valve, Aortic Valve Insufficiency, Mitral Valve Insufficiency, Hypertrophic Cardiomyopathy, Tricuspid Valve Insufficiency

Intervention / Treatment
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* Procedure: Blood Draw


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aortic Stenosis<br>Restricted aortic valve motion and a peak Doppler aortic velocity > 2.5 m/sec blood draw | Procedure: Blood Draw<br>* 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<br>|
| Aortic regurgitation<br>Echocardiographic and Doppler evaluation revealing aortic regurgitation with data adequate to calculate regurgitant volume | Procedure: Blood Draw<br>* 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<br>|
| Aortic valve replacement<br>Mechanical or biological aortic valve replacement | Procedure: Blood Draw<br>* 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<br>|
| Mitral regurgitation<br>Echocardiographic and Doppler evaluation revealing mitral regurgitation with data adequate to calculate regurgitant volume | Procedure: Blood Draw<br>* 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<br>|
| Mitral valve replacement<br>Mechanical or biological mitral valve replacement | Procedure: Blood Draw<br>* 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<br>|
| Hypertrophic cardiomyopathy<br>Patients with known hypertrophic cardiomyopathy who are referred for clinically indicated echocardiography | Procedure: Blood Draw<br>* 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<br>|
| Severe TR with pacemaker / ICD lead<br>Patients referred for clinically indicated echocardiography who have severe tricuspid regurgitation associated with a pacemaker or defibrillator lead documented by echocardiography | Procedure: Blood Draw<br>* 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<br>|
| Prosthetic valve dysfunction<br>Patients with prior heart valve replacement or repair referred for clinically indicated echocardiography who demonstrate stenosis, regurgitation, dehiscence. | Procedure: Blood Draw<br>* 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<br>|
| Normal controls<br>Patients with no heart murmur or history of valve replacement, stenosis, regurgitation, or hypertrophic cardiomyopathy | |
| Left ventricular assist device patients<br>Patients with previously implanted LVAD | |
| Renal dialysis patients<br>Patients on hemodialysis, peritoneal dialysis, or chronic kidney disease with dialysis fistula to be created. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic stenosis, von Willebrand factor, mitral valve replacement, aortic valve replacement, prosthetic valve dysfunction, brain natriuretic peptide, mitral valve regurgitation, aortic valve regurgitation, hypertrophic cardiomyopathy, tricuspid insufficiency