TMAO in Patients With Severe Aortic Stenosis

Study Overview
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Brief Summary
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Trimethylamine N-oxide (TMAO) has recently gained increasing scientific interest in the field of cardiovascular disease, including its role in cell protection against osmotic and hydrostatic stress. Aortic stenosis (AS) is the most common valvular heart disease, affecting about 7.6 million people over 75 years of age in North America and Europe alone. We hypothesized that TMAO plays a role in protection of the cardiomyocytes against pressure overload in patients with AS. The primary aim of this study is to assess the correlation between the serum and urine TMAO concentration, and (i) echocardiographic, (ii) biochemical and (iii) histopathological parameters of heart failure in patients with severe AS. The secondary aim of this study is to evaluate a correlation between the baseline TMAO concentrations and the post-treatment clinical status, as well as the post-treatment echocardiographic and biochemical parameters.

Official Title
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Concentration of Trimethylamine-N-oxide Versus Echocardiographic, Biochemical and Histopathological Parameters of Heart Failure in Patients With Severe Aortic Stenosis: a Prospective, Observatory Trial

Conditions
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Aortic Stenosis, Heart Failure

Intervention / Treatment
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* Diagnostic Test: Measurement of plasma and urine trimethylamine-N-oxide concentration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent to participate in the study Severe aortic stenosis, defined as aortic valve area <1.0 cm2 or aortic valve area index <0.6 cm2/m2 as calculated by the continuity equation on transthoracic echocardiography, regardless of the transvalvular gradient, with or without coexisting symptoms of heart failure Qualification for surgical aortic valve replacement or transcatheter aortic valve implantation by the Heart Team in accordance with European Society of Cardiology guidelines Exclusion Criteria: Heart failure of etiology other than aortic stenosis Coexisting, haemodynamically significant aortic regurgitation Myocardial infarction within the last 3 months Coronary revascularization within the last month or planned during transcatheter aortic valve implantation or surgical aortic valve replacement Chronic kidney disease with estimated glomerular filtration rate <45 ml/min/1.73 m2 Acute gastrointestinal disease within the last month Active neoplastic disease Chronic inflammatory disease Autoimmune disease Chronic intestinal disease Antibiotic therapy within the last 2 months Dietary supplements within the last 7 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe aortic stenosis<br>Patients will be enrolled among those who will be (i) aged from 18 to 99 years, (ii) admitted to the hospital due to severe aortic stenosis, and (iii) qualified for treatment with either surgical aortic valve replacement or transcatheter aortic valve implantation | Diagnostic Test: Measurement of plasma and urine trimethylamine-N-oxide concentration<br>* Information already included in arm/group descriptions.<br>* Other names: N-terminal pro-brain natriuretic peptide measurement, echocardiography, biopsy of a myocardium in patients undergoing surgical aortic valve replacement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the serum and urine trimethylamine N-oxide concentration and aortic valve area index |  | January 15, 2019 - February 15, 2023 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the serum and urine trimethylamine N-oxide concentration and (i) other echocardiographic, (ii) biochemical and (iii) histopathological parameters of heart failure. |  | January 15, 2019 - February 15, 2023 | 
| Correlation between the baseline trimethylamine N-oxide concentrations and the post-treatment clinical status, as well as the post-treatment echocardiographic and biochemical parameters. |  | January 15, 2019 - February 15, 2023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMAO, Aortic Stenosis, Heart Failure, Trimethylamine, Bacterial Metabolites