Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes (CADILACS)

Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes: a Complex Puzzle to be Solved With Potential Therapeutic Implications (CADILACS Study)

Subclinical inflammation plays a critical role in all stages of the atherosclerotic process, from the initiation of the fatty streaks to the development of plaque instability and rupture, causing myocardial ischemia and acute coronary syndromes (ACS).

A few studies have suggested that the autonomic nervous system (ANS) and the inflammatory response are intimately linked. Accordingly, a relation between impaired cardiac autonomic tone and increased markers of inflammation has been reported in healthy subjects as well as in patients with type 1 diabetes mellitus, chronic coronary syndrome or decompensated heart failure.

To get insight in the controversial relationship between cardiac autonomic dysfunction and inflammation in patients with ACS both with and without obstructive CAD and assess the precise mechanisms and molecular pathways by which these two pathophysiological conditions mutually influence each other, to characterize their prognostic implications and identify possible targets for novel therapeutic strategies.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Ischemia; Acute Coronary Syndrome
• Intervention / Treatment: Diagnostic test: Anamnesis and clinical evaluation

Detailed Description

A comprehensive assessment of cardiac autonomic function and inflammatory profile will be performed in ACS patients with obstructive CAD (n=45) or with NO-CAD (n=45) at coronary angiography. In the sub-acute phase (1 to 6 months after the ACS) all patients will undergo a global echocardiographic evaluation, a 24-hour ECG Holter recording to assess HRV and blood samples collection for neurotransmitter measurements, platelet activation and reactivity evaluation and inflammatory profile assessment by proteomics analysis, inflammasome activity evaluation, NLRP3, pro-IL-18 and pro-IL-1β expression level by qPCR and epigenetic analysis. A follow-up to establish clinical conditions of patients will be done after 12 months by direct clinical visit, trans-thoracic echocardiogram to evaluate cardiac remodeling, HRV assessment by 24-hour ECG Holter recording and blood sample collection to evaluate the inflammatory profile as it was assessed at baseline.

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

Contacts and Locations

• Study Contact: Name: Gaetano Antonio GL Lanza; Phone Number: 06 3015 4432; Email: gaetanoantonio.lanza@policlinicogemelli.it

Study Locations

• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS di Roma
      • Contact: Gaetano Antonio GL Lanza; Phone Number: 06 3015 4432; Email: gaetanoantonio.lanza@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years;
• Evidence of previous complete percutaneous revascularization;
• ACS, with or without CAD, experienced in the previous 3 months ±15 days;
• Signed written informed consent.

Exclusion Criteria:

• History of previous acute myocardial infarction (AMI);
• Prior surgical myocardial revascularization via coronary artery bypass graft (CABG);
• Previous incomplete percutaneous myocardial revascularization, as indicated by documentation of residual stenosis >50% or FFR ≤0.8 in any epicardial vessel;
• Killip class III-IV in admission;
• Established cardiovascular disease (assessed by clinical evaluation, physical exam, 12-lead ECG, or transthoracic echocardiogram), such as congenital heart disease, cardiomyopathy, and severe valvular heart disease;
• Serious medical conditions, including severe renal insufficiency (eGFR > 30 ml/min), hepatic insufficiency or cirrhosis, malignancies, COPD (GOLD stage III-IV), and acute or chronic inflammatory diseases;
• Refusal to sign the written informed consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Partecipants with ACS and obstructive CAD; The study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD	Diagnostic test: Anamnesis and clinical evaluation; All partecipants will undergo a global echocardiographic evaluation, a 24-hour ECG Holter recording to assess HRV and blood samples collection for neurotransmitter measurements, platelet activation and reactivity evaluation and inflammatory profile assessment by proteomics analysis, inflammasome activity evaluation, NLRP3, pro-IL-18 and pro-IL-1β expression level by qPCR and epigenetic analysis.; Other Names: Transthoracic Doppler Echocardiography (TTDE);; 24-hour Holter ECG recording;; Peripheral venous blood sampling
Experimental: Partecipants with ACS without CAD, in a 1:1 ratio; Evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography	Diagnostic test: Anamnesis and clinical evaluation; All partecipants will undergo a global echocardiographic evaluation, a 24-hour ECG Holter recording to assess HRV and blood samples collection for neurotransmitter measurements, platelet activation and reactivity evaluation and inflammatory profile assessment by proteomics analysis, inflammasome activity evaluation, NLRP3, pro-IL-18 and pro-IL-1β expression level by qPCR and epigenetic analysis.; Other Names: Transthoracic Doppler Echocardiography (TTDE);; 24-hour Holter ECG recording;; Peripheral venous blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between HRV and CRP parameters in ACS patients with obstructive CAD	The primary endpoint of the study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD. This study will be performed through a detailed history and clinical evaluation based on transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.	12 months
The correlation between HRV and CRP parameters in ACS patients without obstructive CAD	The study is important to identify the differences between HRV and CRP parameters ACS patients without obtructive CAD. It is important to group several exams: sample blood, transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate cardiac autonomic dysfunction associated to a systemic inflammation	To evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography;To evaluate the precise mechanisms and molecular pathways through which cardiac autonomic dysfunction and inflammation influence each other, in order to identify possible targets for new therapeutic strategies;	12 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Autonomic nervous system; Subclinical inflammation; Coronary Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Disease; Myocardial Ischemia; Syndrome; Ischemia; Inflammation; Acute Coronary Syndrome; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: 5480

Drug and device information, study documents

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