Clinical trial NCT05756452: Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes
Official title: Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes: a Complex Puzzle to be Solved With Potential Therapeutic Implications (CADILACS Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Coronary Syndrome
Myocardial Ischemia
Keywords: Subclinical inflammation
Autonomic nervous system
Coronary Syndrome
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-03-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Investigators will enroll partecipants who have had an acute coronary syndrome (3 months ± 15 days before enrollment) followed up at the Cardiology Unit of the participating centers.

Based on the coronary angiography results, partecipants will be divided into two groups:

1. patients with ACS and obstructive CAD;
2. patients with ACS without CAD, in a 1:1 ratio.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The correlation between HRV and CRP parameters in ACS patients with obstructive CAD
timeFrame: 12 months
measure: The correlation between HRV and CRP parameters in ACS patients without obstructive CAD
timeFrame: 12 months
Secondary outcomes:
measure: Evaluate cardiac autonomic dysfunction associated to a systemic inflammation
timeFrame: 12 months
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS di Roma
state: Lazio
Study officials:
References: