Prognosis in Asymptomatic Mitral Regurgitation (PAMIR) Study
Prognosis in Asymptomatic Mitral Regurgitation (PAMIR) Study
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.
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.
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