Heart Failure and Aortic Stenosis Transcriptome

Recruiting

• Conditions: Heart Failure; Aortic Stenosis

• Registration Number: NCT03268135
• Lead Sponsor: IRCCS Policlinico S. Donato

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-05-30
• Study First Submitted: 2017-07-17
• Study First Submitted QC: 2017-08-28
• Study First Posted: 2017-08-31
• Primary Completion: 2024-12-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-04-30
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. 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

2. 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

3. Aortic Stenosis

   • aortic valve replacement
   • intracardial pressure difference >40 mmHg
   • septal diameter ≥1.3 cm

Exclusion Criteria

1. 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

2. 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

3. 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cardiac tissutal mRNAs signatures	from Year 1 to Year 3	The mRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
Cardiac tissutal miRNAs signatures	from Year 1 to Year 3	The miRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
Cardiac tissutal lncRNAs signatures	from Year 1 to Year 3	The lncRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls

Secondary Outcome Measures

Name	Time	Method
Non end-stage, end-stage heart failure, aortic stenosis lncRNAs signatures in plasmas	from Year 3 to Year 5	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
Non end-stage, end-stage heart failure, aortic stenosis mRNAs signatures in plasmas	from Year 3 to Year 5	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
Non end-stage, end-stage heart failure, aortic stenosis miRNAs signatures in plasmas	from Year 3 to Year 5	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

Trial Locations

Locations (2)

Irccs Policlinico San Donato; 🇮🇹 San Donato Milanese, Milan, Italy

Ospedale San Raffaele; 🇮🇹 Milano, Italy