Abstract & Commentary
With Comments by Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco, Editor, Clinical Cardiology Alert.
Source: Gerber IL, et al. Am J Cardiol. 2005;95:898-901.
Valve replacement surgery is usually delayed until symptoms develop in patients with severe aortic stenosis by echocardiography. However, symptoms may be unreliable in older patients who are more sedentary. Thus, Gerber and colleagues from New Zealand evaluated the value of serial BNP measurements to predict the development of symptoms in 29 initially asymptomatic patients with moderate to severe aortic stenosis (peak aortic velocity > 2.5 m/s). The specific assay used was N-terminal pro-brain natriuretic peptide (BNP). Patients with multivessel disease, recent myocardial infarction, or other serious illnesses were excluded. The end point was the development of the classic symptoms of aortic stenosis: dyspnea, angina, or effort syncope. Echocardiograms were performed yearly or at the time of symptoms, and BNP was measured every 6 months.
Results: During a follow-up of 13-23 months, symptoms developed in 8 patients: 7 dyspnea and 1 angina. The patients who developed symptoms were older, had higher peak aortic velocities, and higher baseline BNP levels (75 vs 30 pmol/L, P = .03).
Interestingly, symptoms did not develop in the 8 patients with normal diastolic function. Using a normal upper limit of BNP of 50 pmol/L at baseline, patients with higher values were more likely to become symptomatic (sensitivity 55%). Only 2 patients with lower BNPs became symptomatic (specifically 89%): 1 developed angina and was found to have coronary disease and 1 developed dyspnea at > 18 months, which was associated with an increase in BNP from 25 to 44 pmol/L 6 months before symptoms began and 114 pmol/L at the last visit. The odds ratio for developing symptoms in the 11 patients with BNP > 50 pmol/L vs the 18 with normal values was 10 (95% CI 2-64, P = .02). The OR for peak aortic jet velocity > 4 m/s was 2 (0.4-10, P = .41). Also, over the follow-up period, those who developed symptoms showed a greater rise in BNP (+26 vs +7 pmol/L). Gerber et al concluded that measuring N-terminal proBNP, in addition to clinical assessment and echocardiography, may help better define the timing of aortic valve surgery in moderate to severe aortic stenosis.
Comments
This study supports another use of measuring BNP and promises to help with the sometimes difficult decision of when to operate in aortic stenosis. Clearly, the data do not support this measure as the sole or most definitive measure. Sensitivity for predicting the early onset of symptoms (< 2 years) was only 55%, but specificity was high (89%). Thus, the positive predictive value is high, which would help decide borderline cases. A negative value would be of less utility. Although BNP performed better than peak aortic gradient, this is because you had to have a high peak gradient to get into the study. BNP has to be considered in the entire clinical context, especially during follow-up, when other conditions may supervene which elevate it, such as myocardial infarction, or cause symptoms without elevating it such as angina due to 3-vessel coronary artery disease. Finally, this is a small study with < 2 years of follow-up. A larger, longer study needs to be done, but these results are encouraging and support this use of BNP in the management of aortic stenosis.
Valve replacement surgery is usually delayed until symptoms develop in patients with severe aortic stenosis by echocardiography. However, symptoms may be unreliable in older patients who are more sedentary. Thus, Gerber and colleagues from New Zealand evaluated the value of serial BNP measurements to predict the development of symptoms in 29 initially asymptomatic patients with moderate to severe aortic stenosis.
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