Clinical trial NCT05475028: Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure, Diastolic
Heart Failure, Systolic
Pulmonary Hypertension
Atrial Fibrillation
Keywords: HFpEF
Interactome
CD4+ T cells
HFrEF
Liquid biopsy
Network Medicine
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
Collaborators: name: Monaldi Hospital
name: Federico II University
name: University of Alabama at Birmingham
First posted: 2022-07-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Percentage of differentially methylated regions (DMRs) in CD4+ T cells
timeFrame: 3 months
measure: Levels of differentially expressed genes in CD4+ T cells
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Naples
country: Italy
facility: University of Campania Luigi Vanvitelli
Study officials:
References:
citation: 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.