Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)

NCT05475028 | Completed

• 1 other identifier: UniCampania
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure (HF) is a syndrome, resulting from structural or functional impairment of ventricular filling or ejection of blood. Effective HF management depends on accurate and rapid diagnosis requiring assessment of symptoms and physical signs in combination with advanced and expensive imaging tools. However, several challenges arise from the traditional symptom-based diagnosis because co-morbidities of HF have similar presentations. This implies the need for a deeper knowledge of mechanistic links among genetic and epigenetic events governing the pathophysiology of HF leading to a novel molecular-based system to differentiate HF phenotypes. Now, it is emerging that the pathophysiology of HFpEF and HFrEF is different, it provides an opportunity to identify biomarker candidates that could aid in HF diagnosis and stratification between these two forms of the disease. The aim of PRESMET project is to perform liquid biopsy strategies to identify novel putative non-invasive epigenetic-sensitive biomarkers that could be used either alone or in combination with established diagnostic tests, such as natriuretic peptide, to help differentiate HFpEF from HFrEF. The Investigators will perform DNA methylation analysis on CD4+ T cells isolated from patients versus controls. Remarkably, big data generated from NGS tools will be analyzed by advanced network-oriented algorithms. Our results may provide a useful clinical roadmap in order to improve precision medicine and personalized therapy of HF.

Conditions

Heart Failure, Diastolic; Heart Failure, Systolic; Pulmonary Hypertension; Atrial Fibrillation

Keywords

HFpEF; Interactome; CD4+ T cells; HFrEF; Liquid biopsy; Network Medicine

Outcome Measures

Primary Outcomes (2)

• Percentage of differentially methylated regions (DMRs) in CD4+ T cells

  The Investigators will identify the panel of DMRs able to distinguish HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.

  3 months

• Levels of differentially expressed genes in CD4+ T cells

  The Investigators will measure the levels of gene expression of selected genes (qRT-PCR) in HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.

  1 month

Study Arms (3)

HFpEF

We will recruit HFpEF (LVEF \> 50%)

Other: RRBS

HFrEF

We will recruit HFrEF (LVEF \< 40%)

Other: RRBS

Healthy controls

We will recruit volunteer blood donors

Other: RRBS

Interventions

RRBS OTHER

Reduced Representation Bisulfite Sequencing

HFpEF; HFrEF; Healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Our study population will be composed by: * N=20 HFpEF (LVEF \> 50%) * N=20 HFrEF (LVEF \< 40%) * N=20 healthy subjects

You may qualify if:

• HFrEF (LVEF \< 40%)
• HFpEF (LVEF \> 50%)

You may not qualify if:

• Patients with HF with a history of a reduced LVEF ≤ 40% (HFrEF) who recover LV function (LVEF ≥ 50%)
• Chronic inflammatory diseases
• Cancer

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead
• Monaldi Hospital: collaborator
• Federico II University: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (1)

University of Campania Luigi Vanvitelli

Naples, 80138, Italy

Location

Related Publications (1)

• Napoli C, Benincasa G, Donatelli F, Ambrosio G. Precision medicine in distinct heart failure phenotypes: Focus on clinical epigenetics. Am Heart J. 2020 Jun;224:113-128. doi: 10.1016/j.ahj.2020.03.007. Epub 2020 Mar 12.

  PMID: 32361531 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Genomic DNA will be extracted from circulating CD4+ T cells isolated from peripheral blood of HF patients and healthy subjects

MeSH Terms

Conditions

Heart Failure, Diastolic; Heart Failure, Systolic; Hypertension, Pulmonary; Atrial Fibrillation

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Giuditta Benincasa, Biol.D, PhD

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: July 26, 2022
• Study Start: September 14, 2021
• Primary Completion: January 14, 2022
• Study Completion: June 14, 2022
• Last Updated: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)