Clinical trial NCT03268135: Heart Failure and Aortic Stenosis Transcriptome
Official title: Study of the Transcriptomic Alterations in Heart Failure and Aortic Stenosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Aortic Stenosis
Keywords: miRNA
lncRNAs
transcriptome
heart failure
aortic stenosis
biomarkers
Lead sponsor: IRCCS Policlinico S. Donato
Sponsor class: OTHER
Collaborators: name: Ospedale San Raffaele
First posted: 2017-08-31
Enrollment: 500
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Cardiac surgery patients

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiac tissutal mRNAs signatures
timeFrame: from Year 1 to Year 3
measure: Cardiac tissutal miRNAs signatures
timeFrame: from Year 1 to Year 3
measure: Cardiac tissutal lncRNAs signatures
timeFrame: from Year 1 to Year 3
Secondary outcomes:
measure: Non end-stage, end-stage heart failure, aortic stenosis mRNAs signatures in plasmas
timeFrame: from Year 3 to Year 5
measure: Non end-stage, end-stage heart failure, aortic stenosis miRNAs signatures in plasmas
timeFrame: from Year 3 to Year 5
measure: Non end-stage, end-stage heart failure, aortic stenosis lncRNAs signatures in plasmas
timeFrame: from Year 3 to Year 5
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: Irccs Policlinico San Donato
state: Milan
city: Milano
country: Italy
facility: Ospedale San Raffaele
Study officials:
affiliation: IRCCS Policlinico S. Donato
name: Fabio Martelli, Dr
role: PRINCIPAL_INVESTIGATOR
References: