Genetic and Immunity in Heart Failure (GISCO)

Role of Immunity and Genetic Predisposition in Chronic Heart Failure Exacerbation

Heart failure is a major health problem with serious consequences on mortality and morbidity worldwide. In chronic heart failure an alteration of the inflammatory state occur. The aim of this study will be to describe the relationship between markers of inflammation in patients with heart failure with preserved ejection fraction, gender differences and advanced age.

The study sample will include patients hospitalized in the Unit of General Medicine and Aging with a diagnosis of heart failure based on the guidelines. Clinical and demographic data will be collected from the electronic records of our hospital system. A complete history will be obtained, including the possible etiology of heart failure, cardiac and noncardiac comorbidities, all medications, intracardiac devices, and chronic oxygen treatment. All patients will be documented for peripheral edema, pulmonary rales and jugular vein distension. NYHA (New York Heart Association) class will be identified at discharge. In addition, a blood sample will be taken to obtain a complete panel including total blood count, glycemia, renal function, electrolytes and liver function tests, as per standardized clinical practice. NT-proBNP (Amino-terminal pro Natriuretic Peptide B) will be measured at admission and discharge from the hospital, as per standardized clinical practice.

Echocardiograms will be performed by experienced operators of the echocardiography service of our Polyclinic, according to the American Society of Echocardiography guidelines.

A single additional blood sample will be collected during one of the normal routine blood draws for all immunological tests. Plasma from each participant will be isolated to determine the concentrations of several cytokines. Circulating lymphocytes will be separated according to Ficoll gradient (peripheral blood mononuclear cells, PBMC) into the two different components of immunity (B and T lymphocytes) with different inflammatory phenotypes Evaluation of enhancer (HS)1,2 polymorphisms and estrogen levels: DNA purifications and amplifications will be performed from an aliquot of the single whole blood sample collected for the evaluation of the inflammatory profile. Genomic DNA will be isolated and 9 SNPs in four specific polymorphic regions of the 3'-1 Regulatory Region (3'RR-1) of the human immunoglobulin (IgH) heavy chain locus will be sequenced. Follow-up will be performed by telephone contacting the patients or their caregivers 90 days after discharge.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Genetic: Evaluation of HS1,2 polymorphisms

• Study Type: Observational
• Enrollment (Estimated): 215

Contacts and Locations

• Study Contact: Name: Rossella Cianci; Phone Number: +390630154878; Email: rossella.cianci@policlinicogemelli.it

Study Locations

• Italy
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy
      • Active, not recruiting
      • IRCCS Casa Sollievo della Sofferenza
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Medicina Genarale e dell'Invecchiamento
      • Contact: Rossella Cianci; Phone Number: +390630154878; Email: rossella.cianci@policlinicogemelli.it
      • Principal Investigator: Rossella Cianci

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study sample will include adult patients (>18 years) hospitalized in the Unit of General Medicine and Aging with a diagnosis of heart failure based on the guidelines on heart failure. Clinical and demographic data will be collected from the electronic records of our hospital information system. The medical record of each patient will be used to record demographic and clinical characteristics, data relating to the presentation in the Emergency Department, the evaluation and any event that occurred during hospitalization, including the conditions at discharge.

Description

Inclusion criteria:

• Adult patients (age ≥18 years) with exacerbation of chronic heart failure with reduced or preserved ejection fraction,
• stable haemodynamic conditions, without the need for inotropic support at the time of admission to the ward,
• signature of the informed consent.

Exclusion criteria:

. age <18 years;

• pregnancy;
• acute coronary syndromes;
• end-stage renal failure (clearance <30 mL/min) or dialysis;
• ongoing sepsis;
• bed rest syndrome;
• any concomitant neoplasm,
• congenital and acquired immunodeficiencies (HIV, immunosuppressive drugs).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of HS1,2 enhancer alleles of human immunoglobulin heavy chains in patients with heart failure	Difference in the prevalence of HS1,2 enhancer alleles of human immunoglobulin heavy chains in patients with heart failure with preserved ejection fraction and in patients with heart failure with reduced ejection fraction.	6 months
Inflammatory markers in heart failure	To evaluate any differences in inflammatory markers in patients with heart failure with preserved ejection fraction and reduced ejection fraction, with particular attention to gender and age differences.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic polymorphisms and estrogen levels	Evaluate the association between different genetic polymorphisms and estrogen levels in different models of patients with chronic heart failure with preserved and reduced ejection fraction	6 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Rossella Cianci, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 6721 (PRIISA BA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No