Biomarkers of Inflammation and Fibrosis in Conduction Disorders After TAVI

NCT07201363 | Recruiting FDA Device

• 1 other identifier: 003052401131
• Study Type: observational
• Target: 102
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Aortic Stenosis; Biomarkers; Conduction Disorder; Fibrosis; Inflammation; Transcatheter Aortic Valve Implantation

Outcome Measures

Primary Outcomes (6)

• Pre-procedural levels of C-reactive protein (mg/L) and calprotectin (mg/L)

  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.

  At hospital admission, before TAVI procedure

• Pre-procedural level of interleukin-6 (ng/L)

  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

  At hospital admission, before TAVI procedure

• Pre-procedural levels of procalcitonin (µg/L) and ferritin (µg/L)

  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.

  At hospital admission, before TAVI procedure

• Pre-procedural level of transforming growth factor-β1(pg/ml)

  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.

  At hospital admission, before TAVI procedure

• Pre-procedural level of lactate-dehydrogenase (U/I)

  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

  At hospital admission, before TAVI procedure

• Pre-procedural C-reactive protein to albumin ratio and index of systemic immuno-inflammation values

  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.

  At hospital admission, before TAVI procedure

Secondary Outcomes (5)

• 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

• Myocardial deformation parameters

  At hospital admission, before TAVI procedure

• Left ventricle apical to basal strain ratio

  At hospital admission, before TAVI procedure

• Myocardial work index (mmHg%)

  At hospital admission, before TAVI procedure

• Stage of extravalvular cardiac damage (0-4)

  At hospital admission, before TAVI procedure

Study Arms (2)

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

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

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

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

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

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

Interventions

Biomarkers of inflammation and fibrosis in pre-procedural serum blood samples DIAGNOSTIC_TEST

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.

Also known as: C-reactive protein (CRP), Procalcitonin (PCT), Interleukin-6 (IL-6), CRP/albumin ratio (CAR), Index of Systemic Immuno-inflammation (SII), Lactate-dehydrogenase (LD), Micro ribonucleic acids (miRNAs), Ferritin, Transforming Growth Factor-β1 (TGF-β1), Calprotectin

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

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

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.

Also known as: Stage of extravalvular cardiac damage related to AS, Left ventricle global longitudinal strain (LV GLS), LV apical to basal strain ratio, Right ventricle global longitudinal strain (RV GLS), Right ventricle free wall strain (RV FWS), Myocardial work index (MWI)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The trial will include a minimum 102 consecutive patients with severe AS hospitalized in Clinical Hospital Centre Rijeka for a planned TAVI procedure, according to the previous Heart Team decision.

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Clinical Hospital Center Rijeka: lead
• University of Rijeka, Medical Faculty: collaborator

Study Sites (1)

Clinical Hospital Center Rijeka

Rijeka, Croatia, 51000, Croatia

RECRUITING

Related Publications (10)

• Damas F, Nguyen Trung ML, Postolache A, Petitjean H, Lempereur M, Viva T, Oury C, Dulgheru R, Lancellotti P. Cardiac Damage and Conduction Disorders after Transcatheter Aortic Valve Implantation. J Clin Med. 2024 Jan 11;13(2):409. doi: 10.3390/jcm13020409.

  PMID: 38256543 BACKGROUND

• Ramos-Mondragon R, Galindo CA, Avila G. Role of TGF-beta on cardiac structural and electrical remodeling. Vasc Health Risk Manag. 2008;4(6):1289-300. doi: 10.2147/vhrm.s3985.

  PMID: 19337543 BACKGROUND

• Friedman HS, Zaman Q, Haft JI, Melendez S. Assessment of atrioventricular conduction in aortic valve disease. Br Heart J. 1978 Aug;40(8):911-7. doi: 10.1136/hrt.40.8.911.

  PMID: 687491 BACKGROUND

• Verheule S, Schotten U. Electrophysiological Consequences of Cardiac Fibrosis. Cells. 2021 Nov 18;10(11):3220. doi: 10.3390/cells10113220.

  PMID: 34831442 BACKGROUND

• Hein S, Arnon E, Kostin S, Schonburg M, Elsasser A, Polyakova V, Bauer EP, Klovekorn WP, Schaper J. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003 Feb 25;107(7):984-91. doi: 10.1161/01.cir.0000051865.66123.b7.

  PMID: 12600911 BACKGROUND

• Conte M, Petraglia L, Campana P, Gerundo G, Caruso A, Grimaldi MG, Russo V, Attena E, Leosco D, Parisi V. The role of inflammation and metabolic risk factors in the pathogenesis of calcific aortic valve stenosis. Aging Clin Exp Res. 2021 Jul;33(7):1765-1770. doi: 10.1007/s40520-020-01681-2. Epub 2020 Sep 25.

  PMID: 32978752 BACKGROUND

• Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. doi: 10.1093/eurheartj/ehab395. No abstract available.

  PMID: 34453165 BACKGROUND

• Auffret V, Puri R, Urena M, Chamandi C, Rodriguez-Gabella T, Philippon F, Rodes-Cabau J. Conduction Disturbances After Transcatheter Aortic Valve Replacement: Current Status and Future Perspectives. Circulation. 2017 Sep 12;136(11):1049-1069. doi: 10.1161/CIRCULATIONAHA.117.028352.

  PMID: 28893961 BACKGROUND

• Sammour Y, Krishnaswamy A, Kumar A, Puri R, Tarakji KG, Bazarbashi N, Harb S, Griffin B, Svensson L, Wazni O, Kapadia SR. Incidence, Predictors, and Implications of Permanent Pacemaker Requirement After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2021 Jan 25;14(2):115-134. doi: 10.1016/j.jcin.2020.09.063.

  PMID: 33478630 BACKGROUND

• Spears J, Al-Saiegh Y, Goldberg D, Manthey S, Goldberg S. TAVR: A Review of Current Practices and Considerations in Low-Risk Patients. J Interv Cardiol. 2020 Dec 24;2020:2582938. doi: 10.1155/2020/2582938. eCollection 2020.

  PMID: 33447165 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

An additional sample od blood serum of each patient will be stored for subsequent anaysis of TGF-β1 and calprotectin. In a subpopulation of 40 patients, four specific microRNA will also be analysed from the same stored blood serum samples.

MeSH Terms

Conditions

Arrhythmias, Cardiac; Aortic Valve Stenosis; Fibrosis; Inflammation

Interventions

Echocardiography; Global Longitudinal Strain

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Central Study Contacts

Gordana Bačić, MD

CONTACT

+38551407320; gordana.bacic@uniri.hr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 1, 2025
• Study Start: December 12, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)