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

Sponsor

University of Campania "Luigi Vanvitelli" (Other)

Overall Status

Completed

CT.gov ID

NCT05475028

Collaborator

Monaldi Hospital (Other), Federico II University (Other), University of Alabama at Birmingham (Other)

Enrollment

Location

Actual Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Diastolic Heart Failure, Systolic Pulmonary Hypertension Atrial Fibrillation	Other: RRBS

Detailed Description

The Investigators will perform the first Network Medicine approach to integrate the DNA methylome of circulating CD4+T cells and clinical parameters in patients with HFpEF and HFrEF.

Liquid biopsy strategies will be performed to isolate PBMCs and purificate CD4+ T cells. Successivelly, genomic DNA will be extracted on columns and will be send out for RRBS.

Network-oriented algorithms will be used to analyze DNA methylation signatures and to identify specific epigenetic changes in relation to left ventricle ejection fraction.

Network-oriented DNA methylation signatures will be integrated to the H2FPEF point-of-care calculator and, then, will be validated by the use of q-RT-PCR, WB, and ELISA.

Study Design

Study Type:

Observational

Actual Enrollment :

60 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Network Medicine Approaches to Classify Patients Suffering Heart Failure in Relation to Left Ventricle Ejection Fraction (HFpEF, HFmrEF, HFrEF) by Circulating CD4+ T Cell-derived DNA Methylation Signatures, Clinical Data, and Point-of-care Risk Calculators

Actual Study Start Date :

Sep 14, 2021

Actual Primary Completion Date :

Jan 14, 2022

Actual Study Completion Date :

Jun 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
HFpEF We will recruit HFpEF (LVEF > 50%)	Other: RRBS Reduced Representation Bisulfite Sequencing
HFrEF We will recruit HFrEF (LVEF < 40%)	Other: RRBS Reduced Representation Bisulfite Sequencing
Healthy controls We will recruit volunteer blood donors	Other: RRBS Reduced Representation Bisulfite Sequencing

Arm

Intervention/Treatment

HFpEF

We will recruit HFpEF (LVEF > 50%)

Other: RRBS

Reduced Representation Bisulfite Sequencing

HFrEF

We will recruit HFrEF (LVEF < 40%)

Other: RRBS

Reduced Representation Bisulfite Sequencing

Healthy controls

We will recruit volunteer blood donors

Other: RRBS

Reduced Representation Bisulfite Sequencing

Outcome Measures

Primary Outcome Measures

Percentage of differentially methylated regions (DMRs) in CD4+ T cells [3 months]
The Investigators will identify the panel of DMRs able to distinguish HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.
Levels of differentially expressed genes in CD4+ T cells [1 month]
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.