Heart Failure and Aortic Stenosis Transcriptome (RNA-HF-AS)

Study of the Transcriptomic Alterations in Heart Failure and Aortic Stenosis

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Aortic Stenosis
• Intervention / Treatment: Diagnostic test: measurement of RNAs

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 Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Fabio Martelli, Dr; Phone Number: +39 02 26437762; Email: fabio.martelli@grupposandonato.it

Study Locations

• Italy
  • Milano, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
    • Contact: Michele De Bonis, MD, PhD; Email: debonis.michele@hsr.it
    • Principal Investigator: MICHELE DE BONIS, MD FESC FAHA
  • Milan
    • San Donato Milanese, Milan, Italy, 20097
      • Recruiting
      • IRCCS Policlinico San Donato
      • Contact: FABIO MARTELLI, PhD; Phone Number: 0252774683; Email: fabio.martelli@grupposandonato.it
      • Sub-Investigator: SIMONA GRECO, PhD
      • Sub-Investigator: LORENZO MENICANTI, MD
      • Sub-Investigator: SERENELLA CASTELVECCHIO, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Cardiac surgery patients

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato
• Collaborators: Ospedale San Raffaele
• Investigators: Principal Investigator: Fabio Martelli, Dr, IRCCS Policlinico S. Donato

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2016
• Primary Completion (Actual): December 31, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (Actual): August 31, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; heart failure; miRNA; aortic stenosis; transcriptome; lncRNAs
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: RNA-HF-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No