Increased B-type natriuretic peptide is associated with an abnormal blood pressure response to exercise in asymptomatic aortic stenosis☆
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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Cited by (17)
NT-proBNP for risk stratification of nonagenarian patients with severe symptomatic aortic stenosis
2016, International Journal of CardiologyNatural History, Diagnostic Approaches, and Therapeutic Strategies for Patients with Asymptomatic Severe Aortic Stenosis
2016, Journal of the American College of CardiologyUsefulness of Serial B-type natriuretic peptide assessment in asymptomatic aortic stenosis
2014, American Journal of CardiologyCitation Excerpt :In AS, LVEF at rest, which often remains normal for long, may underestimate the extent of intrinsic myocardial impairment.16 Recently, it has been shown that limited contractile reserve may identify a subset of patients who are at increased risk of abnormal response to exercise and cardiovascular events.17–19 The limited contractile reserve is thus intimately related to latent myocardial dysfunction, which could be easily detected by a significant increase in serial BNP levels.
Natriuretic peptides in aortic stenosis
2012, Revista Portuguesa de CardiologiaCitation Excerpt :Patients with asymptomatic AS and abnormal hemodynamic responses to exercise testing are at increased risk for cardiac events. In asymptomatic or minimally symptomatic AS, higher plasma BNP levels are a better predictor of an abnormal blood pressure response to exercise than echocardiographic measures of aortic valve severity.38 In moderate to severe asymptomatic AS, BNP was associated with lower peak systolic velocity of the mitral valve annulus on exercise and reduced exercise capacity compared with controls.39
Relationship between N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and cardiac cycle efficiency in cardiac surgery
2010, Biomedicine and PharmacotherapyNatriuretic Peptides in Common Valvular Heart Disease
2010, Journal of the American College of CardiologyCitation Excerpt :In contrast to NYHA functional class, angina and syncope do not seem to be related to natriuretic peptides (46,48,58), highlighting the possible different pathophysiologies of these symptoms compared with dyspnea. In asymptomatic or minimally symptomatic AS, higher plasma levels of BNP are a better predictor of an abnormal blood pressure response to exercise than echocardiographic measures of severity (62). In moderate to severe asymptomatic AS, BNP was associated with lower peak velocity of the mitral valve annulus on exercise and reduced exercise capacity compared with controls (63).
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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.