BNP in Chronic Aortic Regurgitation

Abstract & Commentary

By Michael H. Crawford, MD, Editor

Source: Pizarro R, et al. Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation. J Am Coll Cardiol 2011;58:1705-1714.

The most appropriate time to intervene in asymptomatic patients with chronic severe aortic regurgitation is controversial. Since brain natriuretic peptide (BNP) is released by the heart in response to increased wall stress, it has been proposed as a biomarker of the time to intervene in chronic valvular regurgitation patients. Thus, these investigators from Argentina sought to determine the independent prognostic value of BNP in asymptomatic patients with severe aortic regurgitation and normal left ventricular (LV) function. They prospectively evaluated 294 such patients (LV ejection fraction > 55%) using the first 160 patients as the derivation set and the next 134 as the validation set. Severe aortic regurgitation was defined by quantitative echocardiography and lack of symptoms was confirmed by exercise testing. Patients with significant aortic stenosis (peak gradient > 20 mmHg) or other significant valve or cardiac disease were excluded. At least yearly evaluations were done. Mean follow-up of the derivation and validation sets were 46 and 38 months, respectively. The primary endpoint was the appearance of either heart failure or LV systolic dysfunction.

In the derivation set, 28% developed LV systolic dysfunction, heart failure, or death. Three patients (2%) died; two suddenly. Heart failure developed in 18% and LV dysfunction alone in 9%. Aortic valve surgery was performed in 31%. In the validation set, 26% developed the primary endpoint. BNP values were higher in those who developed the primary endpoint vs those who did not (149 vs 48, P = 0.001) in the derivation set with similar values in the validation set. The areas under the ROC curves were 0.84 and 0.82 for the two sets with an optimal cutoff value of 130 pg/mL. This cutoff value had a sensitivity of 77%, specificity of 94%, and negative- and positive-predictive values of 91% and 81% in the validation set. Multivariate analysis of all clinical and echocardiographic variables showed that BNP was the strongest independent predictor of the endpoint (relative risk [RR] 6.7, 95% confidence interval, 2.9-16.9, P < 0.0001) in the validation set. Other significant predictors were end systolic dimension > 24 mm/m2 (RR 3.4), effective regurgitant orifice area > 50 mm2 (4.3), and end diastolic dimension > 35 mm/m2 (2.1). The authors concluded that BNP should be used in the clinical evaluation of asymptomatic patients with severe aortic regurgitation and normal LV systolic function.


This observational study suggests that there is a role for BNP measurements along with echocardiography for evaluating asymptomatic patients with severe aortic regurgitation. This seems like a reasonable recommendation with the caveat that until a trial randomizing patients with BNP > 130 to surgery vs continued medical therapy is done, one should not use BNP as a sole criteria for surgery. Also, experience with early surgery is limited and we do not know if this is a uniformly good strategy. The authors comment that the average time in their study from a BNP > 130 to an endpoint averaged 15 months. Thus, they suggest you can tell the patient that they are probably within 2 years of a defining event. In addition, they note that a rapid increase in BNP predicted events. Those with an event had a greater increase in BNP after 1 year than those without an event (31 vs 9 pg/mL, P = 0.001 in the validation set). Finally, BNP was a better discriminator than the echo parameters they measured.

It is noteworthy that most of their patients were on some pharmacologic therapy, most commonly ACE/ARB. The frequency of any specific medication use was not different between those with or without a BNP > 130 and the authors state that medical therapy did not influence outcomes. However, this should not be construed as a study of medical therapy.

Although observational, this is a well-done study with exercise test confirmed symptom status and quantitative echocardiography. Some might argue that more sophisticated tissue Doppler techniques were not utilized, but there is no evidence that such measures are any better than the standard echocardiographic measures used in this study.