The Role of Left Atrial Fibrosis in Mitral Valve Repair Surgery (ALIVE Trial)

NCT05345730 | Completed DMC

• 1 other identifier: NL78497.018.21
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Patients with mitral valve insufficiency suffer from left atrial remodeling. Atrial fibrosis is part of this remodeling process. The presence of atrial fibrosis is associated with adverse events. Currently, mitral valve repair surgery is the ultimate treatment for severe primary mitral valve insufficiency. The main indications and timing for surgery are severe mitral valve insufficiency with symptoms or left ventricular dysfunction. However, the role of atrial fibrosis in this process remains undetermined despite its well-recognized clinical implications. Characterization of atrial fibrosis patterns in mitral valve insufficiency patients might be potentially valuable for the indication and timing of mitral valve repair surgery in order to improve clinical outcomes. To date, however, mitral valve insufficiency patients suffering from left atrial remodeling have hardly been studied using these new imaging techniques. Therefore, the investigators intend to combine advanced cardiac MRI and post-processing techniques prior to and after mitral valve repair surgery to gain more insight in the clinical implications of atrial fibrosis in this patient population. It is hypothesized that the atrial fibrosis surface area paradoxically will increase after mitral valve surgery because of global shrinkage of the left atrium caused by the reversed remodeling process. As a consequence, more frequently atrial fibrosis related events including (paroxysmal) atrial fibrillation, may be observed in these patients. Objective: To assess the effects of (reduced) volume overload on the left atrial wall texture (presence, amount and location of atrial fibrosis) and associated geometry and function in patients with mitral valve insufficiency, prior to and after mitral valve repair surgery. Study design: Single center pilot study. Study population: The research population consists of mitral valve insufficiency patients scheduled for elective surgical mitral valve repair (N=20) according to the current European guideline criteria.

Conditions

Mitral Valve Disease; Mitral Regurgitation; Surgery; Cardiac Valve Disease; Mitral Valve Surgery; Mitral Valve Repair

Outcome Measures

Primary Outcomes (16)

• Severity of mitral valve insufficiency prior to surgery (regurgitation volume on MRI)

  Severity of mitral valve insufficiency prior to surgery (defined as regurgitation volume in ml calculated using difference between left ventricular stroke volume (LVSV) and forward flow)

  2 weeks before surgery

• Severity of mitral valve insufficiency after surgery (regurgitation volume on MRI)

  Severity of mitral valve insufficiency after surgery (defined as regurgitation volume in ml calculated using difference between left ventricular stroke volume (LVSV) and forward flow)

  3 months after surgery

• Left atrial remodelling prior to surgery (left atrial volume on MRI)

  Left atrial volume (ml) measured by multislice volumetric method on MRI

  2 weeks before surgery

• Left atrial remodelling after surgery (left atrial volume on MRI)

  Left atrial volume (ml) measured by multislice volumetric method on MRI

  3 months after surgery

• Left atrial remodelling prior to surgery (left atrial sphericity on MRI)

  Calculated left atrial sphericity by using ratio of transverse and longitudinal diameters of the left atrium

  2 weeks before surgery

• Left atrial remodelling after surgery (left atrial sphericity on MRI)

  Calculated left atrial sphericity by using ratio of transverse and longitudinal diameters of the left atrium

  3 months after surgery

• Left atrial remodelling prior to surgery (estimated wall tension)

  Estimated wall tension using a calculation combining left atrial wall thickness, left atrial radius and pulmonary wedge pressure. Wall thickness and radius will be measured on MRI. Pulmonary wedge pressure will be measured by using a Swan-Ganz catheter during surgery

  2 weeks before surgery

• Left atrial remodelling after surgery (estimated wall tension)

  Estimated wall tension using a calculation combining left atrial wall thickness, left atrial radius and pulmonary wedge pressure. Wall thickness and radius will be measured on MRI. Pulmonary wedge pressure will be measured by using a Swan-Ganz catheter during surgery

  3 months after surgery

• Presence and distribution patterns of LA fibrosis prior to surgery (quantification of fibrosis surface)

  Quantification of fibrosis surface will be assessed by using dedicated software Cricle ADAS which is able to segment the left atrial wall and recognize fibrotic tissue by means of late gadolinium enhancement

  2 weeks before surgery

• Presence and distribution patterns of LA fibrosis after surgery (quantification of fibrosis surface)

  Quantification of fibrosis surface will be assessed by using dedicated software Cricle ADAS which is able to segment the left atrial wall and recognize fibrotic tissue by means of late gadolinium enhancement

  3 months after surgery

• Presence and distribution patterns of LA fibrosis prior to surgery (geometric distribution of fibrosis)

  Geometric distribution of fibrosis in the left atrium will be assessed using dedicated software Circle ADAS. The software is able to segment the left atrial and define the three-dimensional geometric distribution of fibrotic tissue

  2 weeks before surgery

• Presence and distribution patterns of LA fibrosis after surgery (geometric distribution of fibrosis)

  Geometric distribution of fibrosis in the left atrium will be assessed using dedicated software Circle ADAS. The software is able to segment the left atrial and define the three-dimensional geometric distribution of fibrotic tissue

  3 months after surgery

• Blood flow patterns in the left atrium prior to surgery (flow velocity)

  Blood flow patterns in the left atrium will be assessed by measuring flow velocity using synthetic velocity fields as well as Poiseuille flow. This will be done with dedicated software Circle

  2 weeks before surgery

• Blood flow patterns in the left atrium after surgery (flow velocity)

  Blood flow patterns in the left atrium will be assessed by measuring flow velocity using synthetic velocity fields as well as Poiseuille flow. This will be done with dedicated software Circle

  3 months after surgery

• Blood flow patterns in the left atrium prior to surgery (kinetic energy)

  Kinetic energy of the blood flow patterns will be measured by using dedicated software Circle by means of advanced 4D flow CRM techniques defining global kinetic energy

  2 weeks before surgery

• Blood flow patterns in the left atrium after surgery (kinetic energy)

  Kinetic energy of the blood flow patterns will be measured by using dedicated software Circle by means of advanced 4D flow CRM techniques defining global kinetic energy

  3 months after surgery

Secondary Outcomes (6)

• Change of fibrosis associated biomarkers derived from blood samples (prior to surgery versus after surgery) - NT-proBNP

  2 weeks before surgery and 3 months after surgery

• Change of fibrosis associated biomarkers derived from blood samples (prior to surgery versus after surgery) - TGF-β

  2 weeks before surgery and 3 months after surgery

• Change of fibrosis associated biomarkers derived from blood samples (prior to surgery versus after surgery) - TNF-alfa

  2 weeks before surgery and 3 months after surgery

• Change of fibrosis associated biomarkers derived from blood samples (prior to surgery versus after surgery) - Galectin-3

  2 weeks before surgery and 3 months after surgery

• Change of fibrosis associated biomarkers derived from blood samples (prior to surgery versus after surgery) - MMS

  2 weeks before surgery and 3 months after surgery

Study Arms (1)

Mitral valve insufficiency patients undergoing mitral valve repair surgery

The research population consists of mitral valve insufficiency patients scheduled for elective surgical mitral valve repair (N=20) according to the current European guideline criteria. These patients will undergo a cardiac MRI scan 2 weeks prior to surgery and 3 months after surgery.

Diagnostic Test: 3 DImensional Late Enhanced Gadolinium cardiac MRI scan

Interventions

3 DImensional Late Enhanced Gadolinium cardiac MRI scan DIAGNOSTIC_TEST

A cardiac MRI scan is made using late gadolinium enhancement to detect atrial fibrosis in the left atrium.

Mitral valve insufficiency patients undergoing mitral valve repair surgery

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with mitral valve insufficiency eligible for elective mitral valve repair surgery.

You may qualify if:

• Patients that meet the criteria for elective mitral valve repair surgery according to the European clinical guidelines (class I recommendation);
• Symptomatic, chronic severe mitral valve insufficiency due to degenerative valve disease with a left ventricular ejection fraction \>30%.
• Asymptomatic, chronic severe mitral valve insufficiency due to degenerative valve disease with a left ventricular ejection fraction \<60% and/or a left ventricular end-systolic diameter \>45 mm.

You may not qualify if:

• not able to provide written informed consent.
• under the age of 18.
• with a history of cardiac surgery
• with atrial fibrillation
• with any comorbidity besides mitral valve insufficiency.
• with claustrophobia or any other contra-indication for magnetic resonance imaging

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

AmsterdamUMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Mitral Valve Insufficiency; Heart Valve Diseases

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Jolanda Kluin, M.D., PhD

  j.kluin@amsterdamumc.nl

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Cardiothoracic Surgery

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: April 26, 2022
• Study Start: February 2, 2022
• Primary Completion: July 1, 2023
• Study Completion: December 31, 2023
• Last Updated: July 5, 2024

Record last verified: 2024-07

Locations

NL (1)