Heart Failure and Aortic Stenosis Transcriptome

Study Overview
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Brief Summary
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This study is aimed to investigate the global transcriptome in order to determine the expression profile of messenger RNAs (mRNAs), as well as long noncoding- (lncRNAs) and micro noncoding-RNAs (miRNAs) in heart failure (HF) and in aortic stenosis (AS). The aim is to clarify their role in cardiac disease pathogenesis, as well as their potential as biomarkers. To this purpose, both tissue and blood specimens will be collected and patients will be compared to individuals not affected by cardiovascular diseases.

Detailed Description
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The investigators will collect plasma and cardiac tissue specimens from consenting subjects. The investigators will evaluate the expression of mRNAs, miRNAs and lncRNAs in patients affected by both end-stage and not end-stage HF as well as in patients affected by aortic stenosis and undergoing valve replacement and requiring cardiac myectomy. The tissue dysregulated RNAs will be next measured in plasma samples in order to clarify their potential as biomarkers.

Official Title
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Study of the Transcriptomic Alterations in Heart Failure and Aortic Stenosis

Conditions
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Heart Failure, Aortic Stenosis

Intervention / Treatment
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* Diagnostic Test: measurement of RNAs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non end-stage heart failure left ventricle restoration surgery (SVR) End Systolic Volume Index (ESVI) >35 ml/m2 Ejection Fraction (EF)<40% previous transmural anterior myocardial infarction (MI) age: 40-75 End-stage heart failure left ventricle assisted device (LVAD) surgery age: 40-75 Ejection Fraction (EF) <25% End Systolic Volume Index (ESVI)≥60 ml/m2 Aortic Stenosis aortic valve replacement intracardial pressure difference >40 mmHg septal diameter ≥1.3 cm Exclusion Criteria: Non end-stage heart failure End Systolic Volume Index (ESVI)<35 ml/m2 Ejection Fraction (EF)>40% Time from MI unknown Pregnancy Other genetic diseases Neoplasms Collagenopathies Chemo/radiotherapy Prolonged use of corticosteroids Infections Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and Hepatitis C Virus (HCV) positive End-stage heart failure EF>25% Time from MI unknown Pregnancy Other genetic diseases Neoplasms Collagenopathies Chemo/radiotherapy Prolonged use of corticosteroids Infections Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and Hepatitis C Virus (HCV) positive Aortic Stenosis coronaropathies Pregnancy Other genetic diseases Neoplasms Collagenopathies Chemo/radiotherapy Prolonged use of corticosteroids Infections Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and Hepatitis C Virus (HCV) positive

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non end-stage heart failure<br>Measurement of RNAs in non end-stage heart failure patients undergoing to left ventricle reconstruction | Diagnostic Test: measurement of RNAs<br> <br> |
| End-stage heart failure<br>Measurement of RNAs in end-stage heart failure patients undergoing to left ventricular assisted device (LVAD) | Diagnostic Test: measurement of RNAs<br> <br> |
| Aortic Stenosis<br>Measurement of RNAs in patients affected by cardiac hypertrophy leading to aortic stenosis and requiring cardiac myectomy | Diagnostic Test: measurement of RNAs<br> <br> |
| Controls<br>Measurement of RNAs in individuals not affected by cardiovascular diseases | Diagnostic Test: measurement of RNAs<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac tissutal mRNAs signatures | The mRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 1 to Year 3 | 
| Cardiac tissutal miRNAs signatures | The miRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 1 to Year 3 | 
| Cardiac tissutal lncRNAs signatures | The lncRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 1 to Year 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non end-stage, end-stage heart failure, aortic stenosis mRNAs signatures in plasmas | The mRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 3 to Year 5 | 
| Non end-stage, end-stage heart failure, aortic stenosis miRNAs signatures in plasmas | The miRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 3 to Year 5 | 
| Non end-stage, end-stage heart failure, aortic stenosis lncRNAs signatures in plasmas | The lncRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls | from Year 3 to Year 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcriptome, heart failure, miRNA, lncRNAs, aortic stenosis, biomarkers