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

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Enrolling

Conditions: Myocardial Ischemia; Acute Coronary Syndrome

Treatments: Diagnostic Test: Anamnesis and clinical evaluation

Study type: Interventional

Funder types: Other

Identifiers

NCT05756452

5480

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

90 participants in 2 patient groups

Partecipants with ACS and obstructive CAD

Experimental group

Description:

The study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD

Treatment:

Diagnostic Test: Anamnesis and clinical evaluation

Partecipants with ACS without CAD, in a 1:1 ratio

Experimental group

Description:

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

Treatment:

Diagnostic Test: Anamnesis and clinical evaluation