Clinical trial NCT04406805: TMAO in Patients With Severe Aortic Stenosis
Official title: Concentration of Trimethylamine-N-oxide Versus Echocardiographic, Biochemical and Histopathological Parameters of Heart Failure in Patients With Severe Aortic Stenosis: a Prospective, Observatory Trial
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Aortic Stenosis
Heart Failure
Keywords: Aortic Stenosis
Heart Failure
Trimethylamine
TMAO
Bacterial Metabolites
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2020-05-28
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Correlation between the serum and urine trimethylamine N-oxide concentration and aortic valve area index
timeFrame: January 15, 2019 - February 15, 2023
Secondary outcomes:
measure: Correlation between the serum and urine trimethylamine N-oxide concentration and (i) other echocardiographic, (ii) biochemical and (iii) histopathological parameters of heart failure.
timeFrame: January 15, 2019 - February 15, 2023
measure: Correlation between the baseline trimethylamine N-oxide concentrations and the post-treatment clinical status, as well as the post-treatment echocardiographic and biochemical parameters.
timeFrame: January 15, 2019 - February 15, 2023
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: 1st Chair and Department of Cardiology and Department of Cardiosurgery, Medical University of Warsaw
state: Masovia
Study officials:
References:
citation: 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.