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Neurohormonal markers in the assessment of mitral regurgitation

An article from the e-journal of the ESC Council for Cardiology Practice

Early surgery is increasingly recommended for patients with degenerative mitral regurgitation in order to prevent irreversible decline in left ventricular function.  Plasma brain natriuretic peptide is a more sensitive marker than standard echocardiography in predicting symptomatic progression and offers potential for screening, risk stratification and assessment of prognosis.

Valvular Heart Disease

 The natural history of degenerative mitral regurgitation (MR) is well characterised.  Severe MR is typically tolerated for several years with minimal or absent symptoms while normal left ventricular (LV) systolic function is maintained through compensatory ventricular dilatation.  Longitudinal studies in asymptomatic patients with severe MR demonstrate the high likelihood of symptoms and risk of sudden death within 10 years of diagnosis and the almost inevitable need for surgery.  The onset of symptoms and LV impairment heralds an extremely poor prognosis, with an annual mortality of 34% for those in New York Heart Association functional class III or IV.

Surgery remains the only treatment able to arrest this deterioration in LV function. Valve repair techniques offer low operative mortality, improved long-term survival and post-operative LV function, and decreased likelihood of endocarditis, thromboembolism and need for repeat surgery in comparison with valve replacement.  They may also avoid the hazards of lifelong anticoagulation in many patients.  Thus, early surgery is advised for all patients (even in the absence of symptoms) when predicted operative mortality is low and the likelihood of valve repair is high.

Clinical features associated with poor prognosis include advancing age and the presence of atrial fibrillation or pulmonary hypertension.  However, optimum outcome demands algorithms for the detection of early LV dysfunction.  Current international guidelines advocate serial echocardiographic estimation and referral for surgery when LV ejection fraction falls below 60% or end systolic diameter exceeds 45mm.  This approach has inherent limitations, however, since ejection fraction is often maintained in the presence of LV dysfunction and most sudden deaths occur in asymptomatic patients with normal LV function.  Echocardiography itself has intrinsic disadvantages, often overestimating MR and having technical demand with high interuser variability, particularly in the detection of the subtle early changes of LV impairment.  Whilst newer echocardiographic modalities, notably Doppler tissue imaging, offer promise, the prediction of outcome of mitral surgery remains inaccurate. 

The utility of magnetic resonance, computed tomography and electron beam imaging have been described in the assessment of MR. Particular advantages include the quantitation of regurgitant fraction and assessment of myocardial strain.  However, these techniques may require the use of ionising radiation, are poorly validated, expensive and not always readily available.  In contrast, plasma levels of brain natriuretic peptide (BNP), secreted predominantly from ventricular myocardium in response to increased wall stress, can be measured simply (even at the bedside) and correlate closely with LV dysfunction.  Levels of this neurohormone provide important diagnostic and prognostic information in a wide range of cardiac diseases and have also been recently validated in the assessment of MR.

In a small observational study of 22 patients, Brookes et al noted elevated BNP levels in patients with MR in comparison with normal volunteers.  These levels correlated with symptomatic status but poorly with echocardiographic findings.  During limited follow-up, patients with BNP levels >12pmol/L were most likely to develop symptoms with need for surgery.  In a subsequent more detailed and larger study, Sutton et al examined the relationship between levels of BNP and the symptoms and severity of mitral regurgitation in 49 patients with a range of severities of mitral regurgitation and preserved LV function.  Levels of BNP increased with the severity of regurgitation and were higher in symptomatic patients (see Table).  Again, there was no clear relation to ejection fraction, probably due to the exclusion of patients with abnormal LV function.  Our own unpublished observations have confirmed these findings and also demonstrate a strong correlation between baseline BNP levels and ejection fraction prior to mitral valve repair and at 6 and 12 months follow-up.

Large-scale prospective follow-up data addressing the impact of surgical intervention are now required to validate these early findings.  If confirmed, we anticipate the inclusion of BNP measurement as an essential adjunct in the assessment of MR, particularly in those patients with minimal or no symptoms.  This addition to protocols of assessment at minimal extra cost (20-25 Euros per assay) will allow earliest detection of LV dysfunction and complement the essential anatomical detail already provided by echocardiography.



Cut Point

Sensitivity (%)

Specificity (%)

BNP (pmol/l)




N-BNP* (pmol/l)




ANP** (pmol/l)




Left atrial dimension (cm)




MR score




LV end-systolic dimension (cm)




LVEF (%)




* N-terminal BNP

** Atrial Natriuretic Peptide


The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.



1. Enriquez-Sarano M. Timing of mitral valve surgery. Heart 2002;87:79-85.
2. Agricola E, Galderisi M, Oppizzi M, et al.  Pulsed tissue Doppler imaging detects early myocardial dysfunction in asymptomatic patients with severe mitral regurgitation.  Heart 2004;90:406-410.
3. Brookes CIO, Kemp MW, Hooper J, et al. Plasma brain natriuretic peptide concentration in patients with chronic mitral regurgitation. J Heart Valve Dis 1997;6:608-612.
4. Sutton TM, Stewart RAH, Gerber IL, et al. Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation. J Am Coll Cardiol 2003;41:2280-2287.


Vol3 N°13

Notes to editor

Dr F. F. Syed, Dr S. Ray and Dr B. Prendergast
Manchester, United Kingdom
Nucleus Member of the ESC Working Group on Valvular Heart Disease

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.