Original Title: Natural history, diagnostic approaches, and therapeutic strategies for patients with asymptomatic severe aortic stenosis. Reference: Généreux P et al. J Am Coll Cardiol. 2016; Epub ahead of print.

Given that transcatheter aortic valve replacement (TAVI) is now being prescribed to lower risk patients, some wonder whether it is time to study the benefit of an earlier intervention, when the disease is still asymptomatic, instead of waiting for the symptoms to show, as the guidelines recommend.

Given the complete lack of randomized studies, it is impossible to know whether early intervention could prevent future events in these patients. There is also the question of when is the best time to intervene, and in whom.

In the future, we should design a randomized study to answer these questions, despite running the risk of expanding an expensive procedure to patients that may not need it.

In the CURRENT AS registry, surgical valve replacement in asymptomatic patients with severe AS was associated to lower mortality and lower hospitalization rates for cardiac failure, compared to the traditional conservative strategy.

It seems no one has written the protocol of such randomized study yet, though many researchers think it could happen any time now.

The 2014 AHA/ACC guidelines establish that asymptomatic patients with severe aortic stenosis require close serial clinical and echocardiographic follow up, unless another heart surgery was planned for LVEF < 50%, symptoms appear in a stress test or there is critical stenosis.

In this review published in JACC, P. Généreux and colleagues highlight how difficult it is to determine what patient is really asymptomatic, given the subjective nature of symptoms. Typically, stenosis progresses fairly slowly, which gives patients time for them to find a different cause for their symptoms, or to obliviously adjust their activity or level of exercise to avoid symptoms. They may even deny symptoms to avoid the risk of an intervention.

This JACC review done by P. Généreux analyses data from an observation study on 620 asymptomatic patients; after a 5 year follow up, two thirds of these patients had developed symptoms.

A clinical study of this population could provide baseline data on biomarkers or tolerance to exercise that would be of use to differentiate between patients that can afford to wait vs. those that could benefit from an early intervention.
This potential study could use transcatheter aortic valve replacement (TAVI) vs. surgery, since it would be friendlier for asymptomatic patients, given its less invasive nature.

Another observational study on 200 patients with severe aortic stenosis showed adherent asymptomatic AS patients (those followed up every 6 to 12 months), showed a much higher rate of surgery or TAVI vs. non-adherent patients (47.2% vs 18.3%; p=0.001).

Adherent patients also showed greater survival free from hospitalization for cardiac failure (59.2% vs 52.6%; p=0.02).

What these registries definitely say is that careful follow up is better than the lack of it, but in no way do they provide data on an early strategy of surgical or transcatheter valve replacement.

We should probably be more liberal when giving stress tests to asymptomatic patients, seeing that up to 50% will show positive tests that are a class I indication for replacement, and up to 2% of the asymptomatic population could suddenly die.