Increased B-type natriuretic peptide is associated with an abnormal blood pressure response to exercise in asymptomatic aortic stenosis

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Abstract

Aims

Both raised plasma levels of B-type natriuretic peptide (BNP) and an abnormal exercise response predict adverse clinical outcomes in aortic stenosis (AS). This study examines the relationship between the response to treadmill exercise and plasma levels of BNP in AS.

Methods and results

34 asymptomatic patients with moderate or severe AS (mean valve area 0.96 ± 0.3 cm2) and 15 age matched controls underwent echocardiography, treadmill exercise testing, and BNP analysis. Compared to control subjects, AS patients had a higher left ventricular mass index, (133 ± 50 vs 106 ± 24 g/m2, p = 0.03), higher E/E′ ratio, (10.6 ± 3.6 vs 6.7 ± 1.8, p = < 0.0001), higher ejection fraction, (65 ± 6 vs 59 ± 6%, p = 0.03), elevated resting BNP (11.4 ± 6.5 vs 7.4 ± 4.0 pmol/L, p = 0.03) and shorter exercise duration (8.2 ± 3.0 min vs 10.9 ± 2.6 min, p = 0.002). AS patients with an increase in systolic BP of ≤ 20 mmHg during exercise (n = 18) had higher plasma levels of BNP than patients with an increase in systolic BP > 20 mmHg (13.8 ± 6.1 vs 8.6 ± 6.0 pmol/L, p = 0.003). The BNP measured at peak exercise was also associated with the BP response (p = 0.003). The area under the receiver operator curve to predict an abnormal BP response to exercise was 0.82 for BNP measured at rest but only 0.46 for aortic valve area. There was a modest association between raised BNP and lower exercise capacity.

Conclusion

In patients with AS there is an association between BNP and an abnormal BP response to exercise. Further study is needed to determine the incremental prognostic value of BNP and exercise testing in asymptomatic AS.

Introduction

Treadmill exercise testing and measurement of B-type natriuretic peptide (BNP) have both been proposed to identify apparently asymptomatic patients with aortic stenosis (AS) at higher risk for symptomatic deterioration who may benefit from earlier aortic valve replacement (AVR). Current European Society of Cardiology and American Heart Association/American College of Cardiology guidelines for management of valvular heart disease suggest consideration of surgery for severe AS in asymptomatic patients in whom systolic blood pressure decreases or fails to increase during exercise [1], [2]. This recommendation is based on studies in which patients with an abnormal exercise test were more likely to develop symptoms or have an adverse outcome during follow-up [3], [4], [5], [6]. Despite data on the prognostic value of exercise testing in a European survey only 7% of patients with asymptomatic AS had an exercise test [7]. Low use of treadmill testing may reflect concerns regarding safety, or difficulty interpreting the results, particularly for older patients who have other reasons for decreased exercise capacity.

Plasma levels of BNP are higher in symptomatic compared to asymptomatic patients with AS [8], and in asymptomatic patients a higher plasma BNP or N-BNP level predicts symptomatic deterioration during follow-up [9], [10]. These data suggest that BNP could identify asymptomatic patients who may benefit from earlier AVR. However, there is limited information on the relationship between the plasma level of BNP and the response to exercise in AS. The aim of this study is to determine if plasma BNP is related to a number of exercise parameters, namely short exercise duration, failure of the systolic blood pressure (BP) to rise more than 20 mmHg with exercise, more prominent cardiac symptoms or increasing ST depression during exercise in asymptomatic or minimally symptomatic patients with AS.

Section snippets

Study population

Patients with moderate or severe AS (peak aortic velocity of ≥ 3 m/s) who were asymptomatic, or who had borderline or equivocal symptoms were identified from the Auckland regional outpatient clinics. Exclusion criteria included patients with a history of myocardial infarction, angina or heart failure, left ventricular impairment (ejection fraction < 55%), atrial fibrillation, significant renal disease (creatinine > 0.16 mmol/L), respiratory disease or other significant valvular disease.

Comparison of aortic stenosis patients with normal controls

Baseline demographics, clinical features, echocardiographic measures, exercise treadmill results and plasma BNP levels are shown for normal controls and patients with AS in Table 1. The 34 AS patients and 15 controls were of similar age and the majority were male. The body mass index (BMI) was higher in AS patients. Sixteen AS patients had a history of hypertension. AS patients were more likely to be taking beta-blockers and ACE inhibitors; but systolic BP at rest was similar to controls.

Discussion

In this study higher plasma levels of BNP were associated with an abnormal BP response to exercise in patients with asymptomatic or minimally symptomatic AS. Of note BNP was a better predictor of an abnormal BP response than AVA, resting left ventricular ejection fraction, measures of systolic and diastolic function, or LV mass index.

Two mechanisms have been proposed to explain hypotension during exercise in AS. Firstly, failure to increase cardiac output appropriately. In a study using

Conclusion

This study suggests that in patients with AS who are asymptomatic or with equivocal symptoms the plasma level of BNP predicts an abnormal blood pressure response during exercise, but is a weaker predictor of exercise capacity and angina on treadmill exercise. However it is currently uncertain whether measurement of BNP could replace treadmill exercise testing for evaluation of patients with severe ‘asymptomatic’ aortic stenosis. Prospective outcome studies are needed to determine how

Acknowledgements

This work was supported by project grant 1120 from the National Heart Foundation of New Zealand. Dr Niels van Pelt received support from the Cardiac Trust, Middlemore Hospital, Auckland, New Zealand. Dr Ralph Stewart received funding support from the Green Lane Research and Educational Trust. Gillian Whalley is the National Heart Foundation of New Zealand Senior Fellow. We are very grateful to Jenny White for assistance with study management and to Charlene Nell for assistance with the

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    This work was supported by project grant 1120 from the National Heart Foundation of New Zealand. Dr Niels van Pelt received support from the Cardiac Trust, Middlemore Hospital, Auckland, New Zealand. Dr Ralph Stewart received funding support from the Green Lane Research and Educational Trust. Gillian Whalley is the National Heart Foundation of New Zealand Senior Fellow.

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