Prognosis in Asymptomatic Mitral Regurgitation (PAMIR) Study

• ClinicalTrials.gov Identifier: NCT00509080
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2007
• Last Update Posted: May 4, 2021
• Sponsor: University Hospital, Basel, Switzerland
• Collaborator: Schweizerische Herzstiftung
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

Brief Summary:

The purpose of this study is to determine if the use of BNP/NT-proBNP levels in the detection of early left ventricular dysfunction and damage may improve the timing of cardiac surgery and therefore the long-term management of asymptomatic patients with severe mitral regurgitation.

Condition or disease
Mitral Regurgitation

Detailed Description:

Background: One of the most difficult issues in the care of asymptomatic patients with severe valvular heart disease, particularly mitral regurgitation, is the timing of the surgical intervention. Unlike the stenotic lesions, regurgitant lesions often progress insidiously, causing left ventricular damage before symptoms develop. Current criteria for surgical intervention include left ventricular dimensions and left ventricular ejection fraction. The clinical problem is that once these morphologic criteria are fulfilled, the prognosis has already worsened, even if surgery is performed promptly. In addition, the onset of symptoms may be difficult to detect because of physical inactivity or under-reporting. In some patients, it may be unclear whether symptoms are related to valvular heart disease or other conditions.

Natriuretic peptides including B-type natriuretic peptide (BNP) and NT-proBNP may be more sensitive markers of left ventricular damage than morphologic studies such as echocardiography. The use of BNP or NT-proBNP levels may help timing the surgical intervention before irreversible left ventricular damage has occurred. Previous experience with BNP and NT-proBNP testing in patients with valvular heart disease is limited, albeit promising.

Aim: To test the hypotheses that:

• Elevated BNP/NT-proBNP levels reflect early left and right ventricular dysfunction indicating imminent congestive heart failure and cardiac decompensation, and call for surgical intervention.
• The BNP/NT-proBNP level is a more sensitive marker of ventricular damage than ventricular dimensions and left ventricular ejection fraction.
• Low BNP/NT-proBNP levels indicate a low event rate with medical therapy and may therefore reassure a "wait and see strategy".

Patients and methods: The prospective cohort study is designed to enrol 200 patients with severe mitral regurgitation and followed over a 4-year period. Natriuretic peptides including BNP and NT-proBNP will be measured in addition to detailed clinical, electrocardiographic, and echocardiographic assessment prospectively and repetitively in patients with severe mitral regurgitation during routine consultations at 6 months intervals. Our primary analysis (longitudinal study) will focus on the prognosis in asymptomatic patients. In addition, a sub-study will also include symptomatic patients with severe mitral regurgitation whether or not they are scheduled to undergo valvular surgery (cross sectional study) in order to obtain more reliable data regarding BNP/NT-proBNP levels in patients with a formal indication for valvular surgery. The treating physician will remain blinded to the BNP/NT-proBNP values. In this cohort study, we will try to identify a BNP/NT-proBNP cut-off values that predict major adverse cardiac events including cardiac death, congestive heart failure, myocardial infarction, or persistent left ventricular systolic dysfunction at 6 months after valvular surgery.

Clinical Significance: The use of BNP/NT-proBNP levels in the detection of early left ventricular dysfunction and damage may improve the timing of cardiac surgery and therefore the long-term management of asymptomatic patients with severe mitral regurgitation.

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prognosis in Asymptomatic Mitral Regurgitation (PAMIR) Study
• Actual Study Start Date: April 2006
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Composite of congestive heart failure, decompensated heart failure and valve surgery [ Time Frame: 360 days ]
   Elevated BNP/NT-proBNP levels reflect early left and right ventricular dysfunction indicating imminent congestive heart failure and cardiac decompensation, and call for surgical intervention.
2. Composite of congestive heart failure, decompensated heart failure and valve surgery [ Time Frame: 720 days ]
   Elevated BNP/NT-proBNP levels reflect early left and right ventricular dysfunction indicating imminent congestive heart failure and cardiac decompensation, and call for surgical intervention.

Biospecimen Retention:   Samples Without DNA

Blood samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to the participating centers

Criteria

Inclusion Criteria:

• Patients with severe isolated mitral regurgitation due to valvular disease

Exclusion Criteria:

• Missing written patient consent
• Active infective endocarditis
• Relative mitral regurgitation due to left ventricular disease
• Other moderate to severe dysfunctional valve
• Previous cardiac surgery
• Pregnancy
• Sepsis

Contacts and Locations

Locations

Germany

Herz-Zentrum Bad Krozingen

Bad Krozingen, Germany, 79189

Kerkhoff Klinik

Bad Nauheim, Germany, 61231

Cardiology Praxis Dr. Gekeler

Lörrach, Germany, 79540

Switzerland

Cardiology Praxis Dr. Cron/ Dr. Hess

Basel, Switzerland, 4051

Cardiology Praxis Prof. A. Hoffmann

Basel, Switzerland, 4052

University Hospital of Basel

Basel, Switzerland

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Schweizerische Herzstiftung

Investigators

• Principal Investigator: Christian Mueller, Prof.; University Hospital, Basel, Switzerland

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT00509080
• Other Study ID Numbers: PAMIR
• First Posted: July 31, 2007
• Last Update Posted: May 4, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University Hospital, Basel, Switzerland:

mitral regurgitation; BNP; NT-proBNP; natriuretic peptides; valvular heart disease

Additional relevant MeSH terms:

Mitral Valve Insufficiency; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases