Elderly Asymptomatic Patients With Severe AS Are Often Treated Too Late

In elderly patients with asymptomatic severe aortic stenosis (AS), many die within 3 years and some have mobility issues masking early symptoms that would otherwise indicate the need for valve replacement, a small, prospective study suggests. 

Approximately one-third of elderly patients in the study were unable to exercise, yet exercise testing is the recommended strategy for risk stratifying asymptomatic patients. After diagnosis, the risk of either dying or developing symptoms was 27% at 1 year then 77% and 84%, respectively, at 3 and 4 years. Furthermore, more than 40% of those who eventually developed symptoms had a severe symptom onset (NYHA class III-IV) despite receiving clinical and echocardiographic follow-up every 6 months.

Researchers led by Robert Zilberszac, MD (Medical University of Vienna, Austria), say this severity of onset is likely due to patients being forced by mobility issues to limit their activities. “Symptoms that would otherwise be detected during intense or modest levels of exercise thus remain hidden,” they write. “Ultimately the symptoms become manifest at a more advanced stage with mild exertional activity.”

In an accompanying editorial, Jean-Louis Vanoverschelde, MD, PhD (Université catholique de Louvain, Brussels, Belgium) and Sophie Pierard, MD, PhD (Cliniques Universitaires Saint-Luc, Brussels, Belgium), say the findings highlight the need for “alternative criteria to identify patients at high risk of symptomatic deterioration.”

Rather than exercise testing, they say, peak transaortic flow velocities, which are a strong predictor of outcome, should be considered, with a measure of > 5 m/s being appropriate for valve replacement.

In the study of 103 patients, published online September 14, 2016, ahead of print in JACC: Cardiovascular Imaging, patients with aortic flow velocity ≥ 5.0 m/s had extremely low event-free survival rates of 21% and 6% at 2 and 4 years, respectively, compared with 57% and 23% in those with a velocity < 5.0 m/s (P < 0.001).

Intervention Warranted Before Severe Symptoms

Approximately two-thirds of the patients (69%) underwent aortic valve replacement over the 19.4 months of follow-up, with postoperative survival rates of 89% at 1 year and 77% at 3 years. Of these, about one-third had severe symptom onset.

There was a clear negative impact of severe symptom onset observed for both early and late postoperative all-cause mortality, with 1- and 4-year survival rates of 82% and 46%, respectively, in this group. By contrast, the survival rates were95% and 88% in patients with mild symptom onset.

Vanoverschelde and Pierard assert that asymptomatic severe AS is not a benign disease as commonly thought, adding that the results of the current study “suggest that asymptomatic patients with severe aortic stenosis are being operated on too late and should probably be offered surgery before the onset of severe symptoms, ie at an asymptomatic or minimally symptomatic stage.”

Current American Heart Association/American College of Cardiology (AHA/ACC) practice guidelines state that asymptomatic patients with AS should be followed with a strategy of watchful waiting that involves serial clinical and echocardiographic examinations unless they have LVEF < 50%, are scheduled to undergo other cardiac surgery, have valve-related symptoms that are unmasked by stress testing, have an abnormal exercise stress test, or have hemodynamically very severe AS.

The AHA/ACC guidelines also use a threshold of 5.0 m/s to classify very high transaortic flow velocities, while the European Society of Cardiology guidelines suggest a threshold of 5.5 m/s. According to Vanoverschelde and Pierard, the results of the current study suggest that roughly 50% of patients at the 5.0 m/s threshold will develop symptoms within 1 year of diagnosis.

“In view of the guarded prognosis of those with initial transaortic flow velocities between 4 and 5 m/s, one may wonder whether an even lower threshold should not be considered in the future,” they observe. However, they also note that if more asymptomatic AS patients are to be considered for valve replacement based on this measurement, it is crucial that they also be at extremely low operative risk, particularly if early intervention is going to be considered as an option in younger asymptomatic AS patients.

Is Waiting Just ‘Wishful Thinking’?

“This is a hot topic right now, because severe asymptomatic AS is somewhat of an oxymoron,” said Philippe Généreux, MD (Hôpital du Sacré-Coeur de Montréal, Canada), who was not involved with the study. “The difference between symptomatic and asymptomatic is very subjective, and without appropriate testing we cannot be precise in differentiating the two.”

To TCTMD, Généreux said a trial known as EARLY-TAVR, which is currently under development, may help clarify some of the issues surrounding who and when to treat, as well as how an early minimally invasive approach compares with surgery. In the meantime, he said, the current study illustrates the dangers of watchful waiting.

“I would call it ‘wishful thinking.’ There is a price to pay if you wait too long, and this is what we see in this study,” he observed. “People are being quantified as asymptomatic, and then when they suddenly become symptomatic it’s already too late and they are no longer low-risk patients. I can’t see how we can continue recommending 6-month follow-up when patients are still dying under our watch. Patients who are immobile especially deserve to be risk stratified in a way that makes sense and proves that they really are asymptomatic.”

Sources:

• Zilberszac R, Gabriel H, Schemper M, et al. Asymptomatic severe aortic stenosis in the elderly. J Am Coll Cardiol Img. 2016;Epub ahead of print.  
• Vanoverschelde J-L, Pierard S. Should we reappraise surgical indications in asymptomatic patients with severe high gradient aortic stenosis? J Am Coll Cardiol Img. 2016;Epub ahead of print. 

Disclosures:

• Zilberszac, Vanoverschelde, and Pierard report no relevant conflicts of interest. 

• Généreux reports serving as a consultant and proctor for Edwards Lifesciences.

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