Outcomes in Moderate Mixed Aortic Valve Disease

Impact of Symptoms and Left Ventricular Systolic Function in Patients With Moderate Mixed Aortic Valve Disease

Mixed aortic valve disease (MAVD) is defined as the combination of aortic valve stenosis (AS) and regurgitation (AR) and is relatively frequent, with a reported prevalence up to 20-30% of patients with aortic valve disease. Mortality of patients with moderate MAVD (coexistence of both moderate AS and moderate AR) is largely unknown, and therefore there are currently no guidelines-based indications for surgical or transcatheter intervention for these patients, which is considered only when one of the two lesions (AS or AR) becomes severe. Of note, indication for valve intervention in patients with isolated moderate AS is currently under investigation in several randomized clinical trials but only in the presence of relevant symptoms and signs of left ventricular (LV) dysfunction. One initial single-center study including 250 patients with moderate MAVD has evaluated outcomes in this specific subgroup and showed that patients with asymptomatic moderate MAVD and preserved left ventricular ejection fraction (LVEF) had similar adverse event rates (progression to New York Heart Association (NYHA) class III-IV, aortic valve intervention or cardiac death) to patients with isolated asymptomatic severe AS with preserved LVEF. However, the results were primarily driven by the progression of the NYHA Class and aortic valve replacement, and larger multi-center studies are advocated to confirm these findings, which may therefore identify a (new) group of high risk patients who should in principle benefit from an aortic valve intervention as much as patients with isolated severe AS. In addition, prognostic factors (including clinical and echocardiographic characteristics) for risk-stratification of patients with moderate MAVD have not been identified, which may help to refine the indication for valve intervention and optimize patient management.

Study Overview

• Status: Recruiting
• Conditions: Mixed Aortic Valve Disease

Detailed Description

Hypothesis: Patients with moderate MAVD may have similar mortality rates compared to patients with isolated severe AS or severe AR and therefore benefit from aortic valve intervention. The presence of symptoms or impaired LV function may further identify a higher risk group together with other clinical or echocardiographic parameters.

Objectives:

1. To compare mortality rates in patients with moderate MAVD to isolated severe AS and isolated severe AR in a multi-center setting, adjusting for potential differences in clinical and echocardiographic variables and for the occurrence of aortic valve intervention.
2. To identify clinical and echocardiographic characteristics associated with increased mortality in this specific population and potentially propose dedicated risk scoring and adjusted cut-off values for the various parameters.

• Study Type: Observational
• Enrollment (Estimated): 1900

Contacts and Locations

• Study Contact: Name: Nina Ajmone Marsan, MD, PhD; Phone Number: 31715262020; Email: n.ajmone@lumc.nl
• Study Contact Backup: Name: Jeroen Bax, MD, PhD; Phone Number: 31 (0)71 526 2020; Email: j.j.bax@lumc.nl

Study Locations

• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333ZA
      • Recruiting
      • Leiden University Medical Center
      • Contact: Nina Ajmone Marsan, MD, PhD; Phone Number: 31071262020; Email: n.ajmone@lumc.nl
      • Principal Investigator: Nina Ajmone Marsan, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with concomitant moderate AS and moderate AR, patients with isolated severe AS and isolated severe AR.

Description

Inclusion Criteria:

1. Patients with concomitant moderate AS and moderate AR
2. Patients with isolated severe AS
3. Patients with isolated severe AR

Exclusion Criteria:

1. Previous aortic valve surgery
2. Concomitant left valvular heart disease more than mild grade
3. Acute AR
4. Bad echocardiographic image quality

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Severe Aortic Stenosis
Moderate Mixed Aortic Valve Disease
Severe Aortic Regurgitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	2003-2024

Secondary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality or aortic valve replacement	2003-2024

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Edwards Lifesciences; Queen Mary Hospital, Hong Kong; National Heart Centre Singapore; Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 15, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 23, 2025

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: valvular heart disease; mixed aortic valve disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases
• Other Study ID Numbers: DAP/tak/1662024; THV-I24-181 (Other Identifier: Edwards Lifesciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No