Aortic Stenosis, Conduction Disorder, Permanent Pacemaker Implantation, TAVI(Transcatheter Aortic Valve Implantation)
Conditions
Keywords
Aortic Stenosis, Biomarkers, Conduction Disorder, Fibrosis, Inflammation, Transcatheter Aortic Valve Implantation
Brief summary
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.
Detailed 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.
Interventions
DIAGNOSTIC_TESTBiomarkers of inflammation and fibrosis in pre-procedural serum blood samples
In all patients, peripheral venous blood samples will be collected before the TAVI procedure for analysis and calculation of prespecified inflammatory and fibrosis biomarkers. In a subpopulation of 40 individuals, four specific microRNAs (miR-21, miR-29b, miR-155, and miR-146b) will be additionally analysed. The level of each biomarker will be correlated with rates of new-onset TAVI-related CDs and compared between patients with detected and patients without detected new-onset CDs.
DIAGNOSTIC_TESTTransthoracic echocardiography with myocardial deformation analysis and staging according to the extent of cardiac damage related to AS
The echocardiographic stage of extravalvular cardiac damage related to AS and myocardial deformation parameters will be analysed in each patient before TAVI procedure and compared between the group with detected new-onset CDs and the group without new-onset CDs with a goal to examine their predictive value for the development of TAVI-related CDs.
Sponsors
University of Rijeka, Medical Faculty
Clinical Hospital Center Rijeka
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-procedural C-reactive protein to albumin ratio and index of systemic immuno-inflammation values | At hospital admission, before TAVI procedure | The values of C-reactive protein to albumin ratio and index of systemic immuno-inflammation will be calculated and compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if their values differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs. |
| Pre-procedural levels of C-reactive protein (mg/L) and calprotectin (mg/L) | At hospital admission, before TAVI procedure | The levels of C-reactive protein (mg/L) and calprotectin (mg/L) will be compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if their levels differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs. For calprotectin analysis, an additional serum blood sample will be collected from every patient, and stored at -80 °C for subsequent analysis by the ELISA method. |
| Pre-procedural level of interleukin-6 (ng/L) | At hospital admission, before TAVI procedure | The levels of interleukin-6 (ng/L) will be compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if the levels of interleukin-6 differ significantly between the two groups and to examine its predictive value for the development of TAVI-related CDs |
| Pre-procedural levels of procalcitonin (µg/L) and ferritin (µg/L) | At hospital admission, before TAVI procedure | The levels of procalcitonin (µg/L) and ferritin (µg/L) will be compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if their levels differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs. |
| Pre-procedural level of transforming growth factor-β1(pg/ml) | At hospital admission, before TAVI procedure | The levels of transforming growth factor-β1(pg/ml) will be compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if the levels of TGF-β1 differ significantly between the two groups and to examine its predictive value for the development of TAVI-related CDs. For TGF-β1 analysis, an additional serum blood sample will be collected from every patient, and stored at -80 °C for subsequent analysis by the ELISA method. |
| Pre-procedural level of lactate-dehydrogenase (U/I) | At hospital admission, before TAVI procedure | The levels of lactate-dehydrogenase (U/I) will be compared between the group with new-onset CDs and the group without new-onset CDs. The goal is to determine if the levels of lactate-dehydrogenase differ significantly between the two groups and to examine its predictive value for the development of TAVI-related CDs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial deformation parameters | At hospital admission, before TAVI procedure | Left ventricle global longitudinal strain (%), right ventricle global longitudinal strain (%) and right ventricle free wall strain (%) will be compared between the group with new-onset CDs and the group without new-onset CDs, with a goal to determine if they differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs |
| Left ventricle apical to basal strain ratio | At hospital admission, before TAVI procedure | Values of the left ventricle apical to basal strain ratio will be compared between the group with new-onset CDs and the group without new-onset CDs, with a goal to determine if they differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs |
| Myocardial work index (mmHg%) | At hospital admission, before TAVI procedure | Values of myocardial work index (mmHg%) will be compared between the group with new-onset CDs and the group without new-onset CDs, with a goal to determine if they differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs |
| Stage of extravalvular cardiac damage (0-4) | At hospital admission, before TAVI procedure | Echocardiographic stages of extravalvular cardiac damage (0-4) related to AS will be compared between the group with new-onset CDs and the group without new-onset CDs, with a goal to determine if they differ significantly between the two groups and to examine their predictive value for the development of TAVI-related CDs |
| Pre-procedural levels of microRNAs (miR-21, miR-29b, miR-155, and miR-146b) in a subpopulation of 40 patients | At hospital admission, before TAVI procedure | The levels of four microRNAs included in the regulation of the fibrosis and inflammation process will be analysed and compared between the subgroup with new-onset CDs (20 pts) and the subgroup without new-onset CDs (20 pts). A group of ten healthy individuals will be additionally included for microRNAs analysis. Serum blood samples will be collected at the time of hospitalization, before the TAVI procedure, and stored at -80 °C for subsequent analysis by polymerase chain reaction (PCR). The goal is to determine if their levels differ significantly between the two groups and analyse their correlation with other biomarkers of inflammation and fibrosis |
Countries
Croatia
Contacts
Primary ContactGordana Bačić, MD
Outcome results
None listed