It is still very much a clinical enigma of when to recommend aortic valve replacement for many patients with aortic stenosis. Most clinical decisions have been based on the Ross and Braunwald observation—that survival sharply diminishes as symptoms such as angina, syncope, or heart failure occur. Thus, the guidelines for the treatment of aortic stenosis have put emphasis on whether or not patients are symptomatic. Notwithstanding, we know from exploring data sets and heart surveys of aortic stenosis that the decision for surgery varies from center to center and that aortic valve replacement has been regarded as one of the “softer endpoints.” The “softness” of the aortic valve replacement end point is, of course, not related to the variability in whether aortic valve replacement was actually performed but rather to the observations leading to the decision to perform aortic valve replacement (not limited to the variability in the measurements of symptoms, aortic valve area, and left ventricular systolic function in patients with left ventricular hypertrophy and nonuse of body size indexation).

However, good objective measurements have never been available for the quantification of symptoms. At one extreme, some centers will only recognize symptoms when patients are sedentary and at the other extreme, some centers will have patients perform exercise until they report symptoms. Thus, most clinicians recognize that one of the most important factors for aortic valve replacement is, in fact, not objective but rather, subjective and very much determined by the clinician.

Thus, the European Society of Echocardiography has held pro-et-con session discussions on whether to operate for severe aortic stenosis without symptoms. A good case for aortic valve replacement in the presence of asymptomatic severe aortic stenosis can be justified, because physicians know that extending the observation period is not without potential risk. In a retrospective report from the Mayo Clinic, the omission of surgical treatment was the most important risk factor for late mortality in patients with asymptomatic severe aortic stenosis. In spite this variability, in accordance with the guidelines, many physicians will wait for symptoms to occur, using annual or semiannual clinical examinations and echocardiograms. However, this strategy can result in missing the point at which the left ventricular function is still preserved and will at the same time increase the strongest risk factor for a poor outcome—the patient’s age. Thus, waiting for symptoms in an already elderly and soon to be older patient with reduced left ventricular function could result in missing the opportunity for aortic valve replacement, because surgeons will now decline aortic valve replacement once the patient has become symptomatic. Subsequent to this sad, but not unusual, sequence of events, the patient might be right in asking the caring physician why it was not foreseen that the previously diagnosed, severe, but then asymptomatic, aortic stenosis, later would lead to reduced left ventricular function and older age and thereby deprive the patient of treatment options.

The reason why not all asymptomatic patients with severe aortic stenosis undergo surgery at diagnosis is that clinicians also recognize a dilemma. Although contemporary aortic valve replacement has a low risk of cardiovascular morbidity and mortality, in part because of the strict selection of low-risk patients and in part because of the rejection of patients with greater risk, it remains difficult for clinicians and patients to accept any serious complications in truly asymptomatic patients with aortic stenosis who undergo aortic valve replacement.

The main strength of the report by Dahl et al is that it touches on the major problem in the current clinical standard procedures for the evaluation and timing of aortic valve replacement in patients with severe aortic stenosis. For the clinician, it is crucial to have reliable biomarkers related to symptoms and left ventricular systolic function to better time the recommendation for aortic valve replacement. The study evaluated osteoprotegerin, a new biomarker that encompasses traditional biomarkers and markers of symptoms, such as New York Heart Association functional class, the 6-minute walk test results, and echocardiographic left ventricular systolic function, and related it to the clinical outcome. Although the study was small, it found that increased levels of osteoprotegerin added to the traditional biomarkers in predicting a poor outcome.

As the treatment options for patients with aortic stenosis increase, with percutaneous, surgical, and hybrid aortic valve replacement, treatment will also be offered to older patients with greater cardiovascular risk. Thus, it will be increasing important for clinicians to more precisely risk assess their patients with aortic stenosis, as the demand for clinicians to council patients with regard to the timing of aortic valve replacement increase. In the present study, in which Dahl et al have shown an increased prediction of poor outcome, this new biomarker, osteoprotegerin, could be what clinicians have needed to better council their patients about the timing of aortic valve replacement.