Biomarkers of Inflammation and Fibrosis in Conduction Disorders After TAVI

Clinical Hospital Center Rijeka

Status: Enrolling

Conditions: Permanent Pacemaker Implantation; TAVI(Transcatheter Aortic Valve Implantation); Aortic Stenosis; Conduction Disorder

Treatments: Diagnostic Test: Biomarkers of inflammation and fibrosis in pre-procedural serum blood samples; Diagnostic Test: Transthoracic echocardiography with myocardial deformation analysis and staging according to the extent of cardiac damage related to AS

Study type: Observational

Funder types: Other

Identifiers

NCT07201363

003052401131

Details and patient eligibility

About

Prediction of conduction disorders (CDs) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) is an important and complex process with a significant impact on patient outcomes. The goal of this observational prospective trial is to investigate the role of pre-procedural values of systemic biomarkers of inflammation and fibrosis in the prediction of new-onset CDs and permanent pacemaker implantation (PPI) in patients undergoing the TAVI procedure.

Full description

Transcatheter aortic valve implantation (TAVI) has become an established therapeutic option for the management of severe aortic stenosis (AS) in patients at all levels of surgical risk. Significant improvements in procedural safety and efficacy, along with growing operator experience, have led to a reduction of periprocedural complications. However, the incidence of new-onset conduction disorders (CDs) remains relatively high. This represents a cause for concern, especially regarding the trend of expanding TAVI indication towards younger and lower-risk patients.

Since certain CDs and PPI after TAVI are associated with poorer outcomes, identifying patients at high risk for new-onset CDs is paramount. With careful pre-procedural planning and modification of procedural steps, it is possible to avoid the occurrence of CDs in some patients. After the procedure, more intensive and prolonged electrocardiographic (ECG) monitoring should be applied in patients at high risk. A substantial number of TAVI-related CD predictors have been identified and should be evaluated in every patient, including clinical, electrocardiographic, anatomic, and procedural-related factors.

The process of inflammation and fibrosis plays a significant role in the pathogenesis of degenerative AS, causing not only valvular changes, but also myocardial and conduction system remodeling, with limited research addressing the latter. Circulating biomarkers of inflammation and fibrosis, reflecting the underlying pathological changes of the conduction system, could potentially be correlated with the risk of TAVI-related CDs. Those biomarkers have not been investigated as predictors of the aforementioned disorders so far. Routinely and widely available inflammatory biomarkers could be used in everyday clinical practice as additional predictors for the development of TAVI-related CDs and consequently contribute to an individualized approach in planning the procedure. In accordance with certain more specific and complex biomarkers, analysis of this correlation could also contribute to understanding and clarifying the role of inflammation and fibrosis in the pathogenesis of new-onset CDs in patients undergoing the TAVI procedure.

Trial objective: To investigate the role of pre-procedural values of systemic biomarkers of inflammation and fibrosis in the prediction of new-onset CDs and permanent pacemaker implantation (PPI) in patients with severe AS undergoing TAVI procedure.

Methodology: This is an observational prospective trial that will include a minimum of 102 consecutive patients with severe AS hospitalized in Clinical Hospital Center Rijeka for a planned TAVI procedure, according to the previous Heart Team decision. In all patients, peripheral venous blood samples will be collected before the procedure for analysis and calculation of inflammatory and fibrosis biomarkers (C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), calprotectin, lactate-dehydrogenase (LD), ferritin, CRP/albumin ratio (CAR), index of systemic immuno-inflammation (SII), and transforming growth factor-β1 (TGF- β1). In a patient subpopulation of 40 individuals, four specific microRNAs (miR-21, miR-29b, miR-155, and miR-146b) involved in the regulation of fibrosis and inflammation, will be additionally analyzed. Pre-procedural echocardiographic parameters to assess the extent of extravalvular cardiac damage related to AS and myocardial deformation analysis as a non-invasive marker of fibrosis will be evaluated and correlated with rates of new-onset TAVI-related CDs. The electrocardiogram (ECG) will be analysed before and consecutively after the procedure, during hospitalization, and at a 3-month follow-up. Patients will be assigned to a group with or without new-onset CD, whether a previously defined CD or PPI was recorded during the index hospitalization and follow-up period.

Enrollment: 102 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Written consent to participate in the trial
• Diagnosis of severe AS according to current European Society of Cardiology (ESC) guidelines for valvular heart disease

Exclusion criteria

• Acute infectious disease
• Chronic inflammatory or autoimmune disease
• Corticosteroid or other immunosuppressive therapy
• Active malignant disease
• Liver disease accompanied by dysfunction
• Permanent pacemaker implanted previously
• An acute myocardial infarction within three months before the procedure
• A surgical procedure within three months before the procedure
• Previous surgical or transcatheter aortic valve replacement/implantation
• End-stage chronic kidney disease (eGFR <15 ml/min)

Trial design

102 participants in 2 patient groups

The group with new-onset TAVI-related conduction disorders (CDs)

Description:

The group will include patients with new-onset CD or PPI detected during the index hospitalization and a 3-month follow-up period.

Treatment:

Diagnostic Test: Transthoracic echocardiography with myocardial deformation analysis and staging according to the extent of cardiac damage related to AS

Diagnostic Test: Biomarkers of inflammation and fibrosis in pre-procedural serum blood samples

The group without new-onset TAVI-related conduction disorders (CDs)

Description:

The group will include patients without new-onset CD or PPI detected during the index hospitalization and a 3-month follow-up period.

Treatment:

Diagnostic Test: Transthoracic echocardiography with myocardial deformation analysis and staging according to the extent of cardiac damage related to AS

Diagnostic Test: Biomarkers of inflammation and fibrosis in pre-procedural serum blood samples