Molecular Pathways of Cardiac Remodellation in Patients With Acute and Chronic Left Ventricular Disfunction (HFrEF)

Molecular Pathways of Cardiac Remodellation in Patients With Acute and Chronic Left Ventricular Disfunction (HFrEF)

Chronic heart failure represents an extremely complex clinical syndrome, defined as the inability of the heart muscle to generate a volume adequate to the metabolic needs of peripheral tissues, or to do so only in the face of high filling pressures intracavity. Heart failure is one of the leading causes of mortality and morbidity in Western countries.

Despite advances in the therapeutic field, the prognosis of patients with heart failure of ischemic and non-ischaemic aetiology still remains unfavorable, with a mortality rate of 50% 5 years after the first hospitalization.Therefore, a deeper understanding of the pathophysiological mechanisms involved in heart failure and adverse ventricular remodeling is essential.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Ischemic Cardiomyopathy
• Intervention / Treatment: Other: Blood sample

Detailed Description

The study will be interventional, prospective, and single-center. Partecipants will be divided into three groups:

1. 30 partecipants admitted to our hospital with the diagnosis of STEMI-type ACS and ejection fraction ≤ 35% on echocardiographic evaluation
2. 30 partecipants with non-ischaemic dilated cardiomyopathy and ejection fraction ≤35% on echocardiographic evaluation
3. 15 partecipants diagnosed with STEMI-type ACS and ejection fraction > 50% on echocardiographic evaluation
4. 15 controls with normal left ventricular contractile function. The study foresees a phase of patient recruitment, in which, in the hours immediately following the blood sampling, the isolation of the PBMCs, their incubation and cytofluorimetric analysis will be carried out and the conservation of the material to be analyzed subsequently by molecular biology and immunochemistry.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients admitted to the Gemelli Polyclinic with acute coronary syndromes and heart disease;
• patients admitted to our polyclinic with the diagnosis of SCA type STEMI and ejection fraction ≤ 35% at echocardiographic evaluation;
• patients with non-ischemic dilated cardiomyopathy and ejection fraction ≤ 35% at echocardiographic evaluation;
• patients diagnosed with SCA type STEMI and ejection fraction > 50% at echocardiographic evaluation;

Exclusion Criteria:

• evidence of inflammatory or infectious disease;
• malignancy, or immunological or hematologic disorders;
• treatment with anti-inflammatory drugs other than low-dose aspirin;
• age > 85 years;
• recent surgery (within one month);
• advanced chronic kidney disease (eGFR MDRD-4 <30 ml/min./1.73m2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with acute coronary syndrome; 30 patients admitted to our hospital with the diagnosis of STEMI-type ACS and ejection fraction ≤ 35% on echocardiographic evaluation	Other: Blood sample; The study foresees a phase of patient recruitment, in which, in the hours immediately following the blood sampling, the isolation of the PBMCs, their incubation and cytofluorimetric analysis will be carried out and the conservation of the material to be analyzed subsequently by molecular biology and immunochemistry.; Other Names: Molecular pathway and protein
Other: Patients with non-ischaemic dilated cardiomyopathy; 30 patients with non-ischaemic dilated cardiomyopathy and ejection fraction ≤35% on echocardiographic evaluation	Other: Blood sample; The study foresees a phase of patient recruitment, in which, in the hours immediately following the blood sampling, the isolation of the PBMCs, their incubation and cytofluorimetric analysis will be carried out and the conservation of the material to be analyzed subsequently by molecular biology and immunochemistry.; Other Names: Molecular pathway and protein
Other: Patients diagnosed with STEMI-type ACS; Patients diagnosed with STEMI-type ACS and ejection fraction > 50% on echocardiographic evaluation	Other: Blood sample; The study foresees a phase of patient recruitment, in which, in the hours immediately following the blood sampling, the isolation of the PBMCs, their incubation and cytofluorimetric analysis will be carried out and the conservation of the material to be analyzed subsequently by molecular biology and immunochemistry.; Other Names: Molecular pathway and protein
Other: Controls; Controls with normal left ventricular contractile function	Other: Blood sample; The study foresees a phase of patient recruitment, in which, in the hours immediately following the blood sampling, the isolation of the PBMCs, their incubation and cytofluorimetric analysis will be carried out and the conservation of the material to be analyzed subsequently by molecular biology and immunochemistry.; Other Names: Molecular pathway and protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of molecular pathways involved in acute cardiac dysfunction and cardiac remodelling	Gene expression assessment of molecular pathways involved in acute cardiac dysfunction and cardiac remodelling underlying reduced ejection fraction heart failure (HFrEF). Evaluation of protein expression of specific markers by means of cytofluorimetric and immunochemical methods, the choice of which will be made after the analysis of the molecular gene patterns most commonly represented in patients with left ventricular contractile dysfunction.The study includes a patient recruitment phase, in which the isolation of PBMCs, their incubation and cytofluorimetric analysis will be carried out in the hours immediately following the blood sampling, and the material will be stored for subsequent analysis by molecular biology and immunochemistry analysis.	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Experiments to identify possible molecular targets for future studies	Carrying out mechanistic experiments to verify the biological significance of altering specific molecular patterns and identifying possible molecular targets for subsequent studies. For these future studies, it is planned to store material for retrospective analysis by molecular biology and immunochemistry.	6 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): January 7, 2020
• Study Completion (Anticipated): December 10, 2023

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Ejection Fraction (EF); Sympathetic nervous system (SNS); Renin-angiotensin-aldosterone system (RAAS)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: 2291

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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