TMAO in Patients With Severe Aortic Stenosis (TASTE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Aortic Stenosis
• Intervention / Treatment: Diagnostic test: Measurement of plasma and urine trimethylamine-N-oxide concentration

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Aleksandra Gąsecka, MD; Phone Number: +48225991951; Email: gaseckaa@gmail.com

Study Locations

• Poland
  • Masovia
    • Warsaw, Masovia, Poland
      • Recruiting
      • 1st Chair and Department of Cardiology and Department of Cardiosurgery, Medical University of Warsaw
      • Sub-Investigator: Monika Budnik, PhD
      • Contact: Aleksandra Gąsecka, PhD; Phone Number: +48225991951; Email: gaseckaa@gmail.com
      • Principal Investigator: Agnieszka Kapłon-Cieślicka, Ass. Prof.
      • Sub-Investigator: Aleksandra Gasecka, PhD
      • Sub-Investigator: Michał Konwerski, MD
      • Sub-Investigator: Marcin Ufnal, Prof.
      • Sub-Investigator: Radosław Wilimski, PhD
      • Sub-Investigator: Paweł Czub, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients will be enrolled among those who will be (i) aged from 18 to 99 years, (ii) admitted to the 1st Chair and Department of Cardiology or Department of Cardiosurgery, Medical University of Warsaw due to severe AS, and (iii) qualified for treatment with either surgical aortic valve replacement or transcatheter aortic valve implantation.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe aortic stenosis; 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; Information already included in arm/group descriptions.; 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?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Medical University of Warsaw

Publications and helpful links

General Publications

• Jaworska K, Hering D, Mosieniak G, Bielak-Zmijewska A, Pilz M, Konwerski M, Gasecka A, Kaplon-Cieslicka A, Filipiak K, Sikora E, Holyst R, Ufnal M. TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology. Toxins (Basel). 2019 Aug 26;11(9):490. doi: 10.3390/toxins11090490.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Anticipated): February 15, 2022
• Study Completion (Anticipated): February 15, 2023

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Heart Failure; Aortic Stenosis; Trimethylamine; TMAO; Bacterial Metabolites
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Aortic Valve Stenosis; Constriction, Pathologic; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: KB/211/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The individual participant shared only in case the identity of the participant has been made unrecognizable.

Drug and device information, study documents

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