Study of the Expression of Autophagy Markers in the Myocardium in Patients With Persistent or Permanent Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— MIPAR-02  

Official title:

Study of the Expression of Autophagy Markers in the Myocardium in Patients With Persistent or Permanent Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05850039
• Other study ID #: MIPAR-02
• Status: Recruiting
• Start date: April 9, 2019
• Est. completion date: June 9, 2024

Study information

• Verified date: April 2023
• Source: Ospedale San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Atrial Fibrillation (AFib) is the most common cardiac arrhythmia, causing the loss of the normal and coordinated atrial contractility.

Several studies have demonstrated the existence of some atrial anatomical sites involved in the initiation and maintenance of this arrhythmia, first of all the posterior wall in the area around the outlet of the pulmonary veins. In fact, the existence of a complex of structural and functional modifications has been documented, collectively defined as "structural remodeling" which involve both the cardiomyocyte and the interstitium (the space between the cardiomyocytes) from a histopathological point of view; at the cardiomyocyte level, a loss of sarcomeres in the perinuclear site (myocytolysis), a reduction in the expression of "adult" cellular proteins (e.g. cardiotin and titin) with concomitant re-expression of "fetal" proteins (e.g. muscle actin smooth), as well as a modification of the mitochondrial structure. At the interstitial level, remodeling is characterized by the deposition of fibrous tissue in the interstitium between the muscle bundles and by a reduction in capillary density. Regarding the deposition of collagen fibers, some studies on an experimental model of AFib have shown that the latter is not reversible.

Autophagy is an intracellular process regulated by numerous biochemical signals; it is present at basal levels in most tissues and allows the physiological turnover of the various structural components of the cell, directing them to lysosomal degradation. It can also be stimulated by external signals in unfavorable environmental conditions, such as in the case of pathologies that determine a condition of tissue oxidative stress protracted over time. Experimentally, an excessive activation of the latter has been associated with the early stages of pathological cardiac remodeling in various animal models of cardiovascular diseases and some recent studies have hypothesized that altered levels of autophagy may contribute to the possible mechanisms involved in the generation and maintenance of the remodeling cardiomyocyte and interstitial structure in AFib. The levels of autophagic activity can be evaluated by studying specific markers - such as the Beclin-1 and LC3B proteins - constituents of the autophagic signaling cascade. In the case of LC3B, the "LC3BII/LC3BI" ratio (the processed form of autophagosomal vesicles and the unprocessed form constitutively present at the cytoplasmic level) was used as an autophagy biomarker. Furthermore, some microRNAs (miRNAs) capable of controlling the expression of proteins of the autophagic cascade have been described in the literature. This is the case of miRNA 30a and miRNA 204, respectively, which respectively inhibit the expression of Beclin-1 and of LC3B.

This study aims to investigate from a histo-morphological and molecular point of view the presence of alterations of autophagy mechanisms in patients with persistent or permanent AFib and which correlate these modifications with the degree of structural remodeling present at the level of the left atrial myocardium.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: June 9, 2024
• Est. primary completion date: April 9, 2024
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Group 1 - Study Inclusion criteria

• Age between 18 and 85 years old

• Permanent or persistent AFib for which the patient undergoes ablation surgery surgery of atrial fibrillation with isolated radiofrequency or associated with possible correction of heart valve disease with or without coronary artery disease Exclusion criteria

• Age < 18 years

• Need for emergency cardiac surgery

• Presence of concomitant systemic inflammatory diseases

Group 2 - Control Inclusion criteria

• Age between 18 and 85 years old

• Sinus rhythm at the time of admission for surgery

• No AFib in history

• Hospitalized for correction of isolated mitral valve disease or associated with correction of other valve diseases Exclusion criteria

• Age < 18 years

• Need for surgical coronary revascularization

• Need for emergency cardiac surgery

• Presence of concomitant systemic inflammatory diseases

Group 3 - Autoptic control Inclusion criteria

• Age between 18 and 85 years old Exclusion criteria

• No signs of post-mortal tissue decomposition assessed by histological examination

• Documented history of arrhythmias, valvular dysfunction, atherosclerosis of the coronary arteries, previous myocardial infarctions, foci of myocardial fibrosis greater than 2 mm on histology, presence of inflammatory cells in the interstitium, sarcoidosis, amyloidosis, chronic inflammatory lung diseases and connective tissue diseases.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Other:
• Sampling
Sample collection: a small fragment of atrial wall will be collected

Locations

Country	Name	City	State
Italy	IRCCS Ospedale San Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beclin-1 and LC3B levels in blood		Baseline