• aortic stenosis
• inflammatory markers
• valvular heart disease

Calcified aortic stenosis (AS) is the most common form of valvular heart disease in the developed world. Severe AS has >7% prevalence among those older than 80 years.1 Current guidelines recommend aortic valve intervention with a class I indication for patients with symptomatic severe AS. Indications have been expanded for asymptomatic patients with severe AS to include those with a left ventricular ejection fraction (LVEF) of <50%, a positive exercise stress test, decreased blood pressure on stress testing or critical AS (specifically peak aortic jet velocity (Vmax) ≥5 m/s). However, the management of patients with asymptomatic severe AS who are not covered by these recommendations still represents a clinical conundrum. A close surveillance (‘watchful waiting’) strategy is usually adopted in this situation, and decisions are made on an individual basis. Some patients with asymptomatic severe AS and normal LVEF are inevitably more vulnerable to future adverse events than others; therefore, the identification of potential biomarkers that might be helpful in the risk stratification of these patients is of particular importance.

In their Heart paper, Nakatsuma et al 2 present a commendable study including a large multicentre cohort of 387 patients with asymptomatic severe AS and a mean age of 80 years from the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry. The authors report that B-type natriuretic peptide (BNP) levels are associated with a higher risk for AS-related adverse events in asymptomatic severe AS with normal left ventricular ejection fraction. These data could support the incorporation of BNP into the management of these patients and suggest that regular measurement of BNP levels may be a good safety monitor. CURRENT-AS asymptomatic patients with BNP <100 pg/mL had a low event rate for ‘aortic valve-related death or heart failure hospitalisation’ (2% at 1 year), and those with BNP <300 pg/mL had a low rate of sudden death (1% at 1 year) and aortic valve-related death (2% at 1 year). This information is in alignment with the one reported by the Influencia del Diagnóstico de Estenosis Aórtica Severa—Influence of the Severe Aortic Stenosis Diagnosis registry,3 in which the mortality of patients receiving conservative treatment in the absence of significant symptoms was 2.9% at 1 year. Most patients with severe AS are elderly and present comorbidities, and transcatheter aortic valve implantation (TAVI) may be the treatment of choice in some of these cases. However, other clinical variables also influence this decision, and even patients with high BNP may not benefit from an intervention if they have cognitive dysfunction, frailty or other relevant comorbidities4 (figure 1). Further, some variables such as significant mitral regurgitation might be related to a poor prognosis,5 but their presence could favour a decision for conservative treatment.6 TAVI has not been previously studied in patients with asymptomatic severe AS; however, low procedural complication rates, short hospital length of stay, zero mortality and zero disabling stroke at 30 days were reported in a recent study of low-risk patients with symptoms, which may be the most similar scenario.7

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Figure 1

A suggestion to incorporate B-type natriuretic peptide in the current guideline recommended approach in patients with asymptomatic severe aortic stenosis. AS, aortic stenosis; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; Vmax, peak aortic jet velocity.

The current study is not without limitations deserving comment. The assessment of symptomatic status in mostly elderly patients is not a trivial issue and may be influenced by patients’ sedentary lifestyles and non-specific symptoms including fatigue and dyspnoea on exertion. This retrospective study includes the participation of 27 recruiting centres, and it is therefore of utmost importance to confirm that symptoms were detected in the same way by all involved investigators. Elderly patients are considered ‘asymptomatic’ too often because they do not refer with active symptoms, while a careful interrogation may easily indicate that these patients move progressively less, which is itself a surrogate of symptoms. We believe that a positive stress test may be particularly useful in some of these patients. In this setting, an exercise test may be considered abnormal in the presence of (1) angina, syncope or presyncope; (2) dyspnoea or maximal exhaustion to functional capacity (5 Metabolic equivalents (METS) in patients aged <70 years or 4 METS in patients aged >70 years); (3) decrease in systolic blood pressure of >20 mm Hg; (4) ST-segment depression of >2 mm; or (5) more than three consecutive ventricular premature beats or ventricular tachycardia during exercise or recovery. This was unfortunately not conducted in the present study, leaving the ‘asymptomatic’ designation not completely incontrovertible.

The value of natriuretic peptides in patients for severe AS is well known, yet they have not been readily incorporated into clinical guidelines or regular management due to the lack of outcomes trials using BNP to guide the intervention. BNP is a strong independent predictor of cardiovascular death regardless of symptomatic status. A new risk calculation parameter in AS is BNP ratio (measured BNP/maximal normal BNP value for age and sex), representing BNP activation. A preliminary report showed that BNP activation was not only an independent predictor of survival but also a prognosis predictor in a subgroup of patients with asymptomatic AS, normal ejection fraction and no history of myocardial infarction.8 Therefore, BNP ratio appears to offer better prognostic value for asymptomatic severe AS patients than BNP value alone, although additional validation data are required.

In conclusion, while the results of randomised trials in asymptomatic severe AS using biomarkers to guide decisions are pending, every effort should be made to improve risk stratification in these patients. The present study suggests that patients with the highest BNP levels may require closer follow-up and eventually early valve replacement with TAVI or surgical aortic valve replacement (figure 1). While the role of biomarkers is promising, they must be thoroughly examined in clinical trials before entering into clinical practice. In the meantime, biomarker research is welcome to improve understanding of patients’ phenotypes and clinical progression.