Natriuretic Peptide Levels in Mitral Regurgitation

Abstract & Commentary

Synopsis: Plasma natriuretic peptides are related to the severity of mitral regurgitation and the presence of symptoms but not LV size or function.

Source: Sutton TM, et al. J Am Coll Cardiol. 2003; 41:2280-2287.

Decisions regarding appropriate therapy in patients with mitral regurgitation depend on an accurate assessment of the severity of regurgitation. Although echocardiograpy is the preferred method for making this determination, it is a technically demanding challenge without generally agreed upon criteria. Thus, another complementary approach would be welcomed to this endeavor. Accordingly, Sutton and colleagues from New Zealand explored the concept that natriuretic peptide levels (ANP, BNP) may aide in the determination of the severity of mitral regurgitation. They selected 49 patients with isolated mitral regurgitation and left ventricular ejection fraction (LVEF) > 55% for the study. All patients had a complete echocardiographic assessment and 3 natriuretic peptide levels measured. They also studied 100 normal controls. The majority of patients had mitral valve prolapse (33) but 15 had rheumatic disease, 4 of whom had mild mitral stenosis (valve area < 1.5 cm2). Symptoms were present in 33 patients, and 16 were asymptomatic. Symptomatic patients more often had atrial fibrillation, more severe regurgitation, and larger left atria. Other characteristics including LV size and EF were not different in symptomatic patients. Natriuretic peptide levels rose with increasing severity of regurgitation and left atrial size but were unrelated to LV size and function. Symptomatic patients had higher natriuretic peptide levels as compared to asymptomatic patients (BNP 17 vs 7 pmol/L, P < .001), and asymptomatic patients had higher levels than controls (BNP 5 pmol/L, P < .0001). Accuracy for predicting symptoms was .89-. 90 (area under the receiver operating curve) for the natriuretc peptides, .88 for the mitral regurgitation index,1 .81 for left atrial size, and .63 for LV size. Sutton et al concluded that plasma natriuretic peptides are related to the severity of mitral regurgitation and the presence of symptoms but not LV size or function.

Comment by Michael H. Crawford, MD

There are 2 major frustrations in the evaluation of patients with mitral regurgitation. By far, the greatest is determining the severity by echocardiography. Since there is no one measurement technique that all agree is adequate for this purpose, some labs use combinations of findings or one of the published indexes, but most labs just use a qualitative visual assessment for which there are no universally agreed criteria. Hence one reader’s mild is another’s moderate regurgitation. Some stick to mild, moderate, and severe, and other labs use a 6-point differentiation system. This unsatisfactory situation begs for another technique to determine the severity of mitral regurgitation. Are natriuretic peptides the answer? Probably not. In this study, they were related to regurgitation severity and symptoms in general, but they are unlikely to be precise enough in an individual patient for clinical decision-making. In fact, the limited clinical follow-up information provided in this paper confirms this limitation: One asymptomatic patient who developed worsening LV function and symptoms and was referred for surgery had a BNP level of 4 pmol/L.

The other problem with evaluating patients with mitral regurgitation is determining if they have symptoms related to the valve lesion, since such symptoms as dyspnea and fatigue are nonspecific. Will natriuretic peptide levels help in this assessment? Perhaps. In this study, there was a clear relationship to symptoms, and all the patients with symptoms referred for surgery had elevated levels of BNP (11-52 pmol/L). The real question is whether natriuretic peptide levels will be of value for following asymptomatic patients to determine the timing of operation. This study was not designed to answer that question, but it does support the concept enough that perhaps a trial is in order.

There are limitations to the use of natriuretic peptides for these purposes that must be addressed. Natriuretic peptides increase with age, are higher in women than in men, and are inversely related to body surface area. Obviously these factors need to be taken into consideration and currently there is no easy way to do this. Also, the value of natriuretic peptides in patients with enlarged LVs or reduced LV function and mitral regurgitation is unclear since such patients were excluded from this study. It would be expected that these findings would raise natriuretic peptide levels regardless of mitral regurgitation, but more information is needed in this regard. Of interest in this study was the finding that natriuretic peptides were related to left atrial size. Previous studies have shown that left atrial enlargement is a poor prognostic sign in chronic mitral regurgitation, perhaps because it foreshadows the development of atrial fibrillation. This relationship may be another strength of measuring natriuretic peptides in mitral regurgitation patients. In summary, measuring natriuretic peptides in mitral regurgitation patients may be of value for discerning significant symptoms from nonspecific ones and may contribute to the determination that severe mitral regurgitation exists, but the limitations of this one measurement need to be taken into consideration. 

Dr. Crawford, Professor of Medicine, Associate Chief of Cardiology for Clinical Programs, University of California, San Francisco, is Editor of Clinical Cardiology Alert.


1. Thomas L, et al. J Am Coll Cardiol. 1999;33:2016-2022.