Long-term survival poor in patients with moderate, severe AS

Both severe and moderate aortic stenosis (AS), when left untreated, were associated with poor long-term survival in a large-scale study of Australian heart patients.

First author Geoff Strange, PhD, of the University of Notre Dame in Western Australia, and colleagues published their findings in the Journal of the American College of Cardiology, noting they launched their study in response to a lack of information about long-term survival in patients across the AS spectrum. We’ve known for awhile now that untreated severe AS yields poor outcomes, but it’s less clear how patients with mild and moderate diagnoses fare.

As transcatheter aortic valve replacement (TAVR) has risen in popularity over the past several years, it’s started to eclipse surgical AVR (SAVR) as a first-line treatment for people with aortic stenosis, the authors said. A handful of randomized clinical trials—including the groundbreaking PARTNER 3 trial—have demonstrated the noninferiority of TAVR in respect to long-term mortality and CV risk when compared with SAVR in low-risk patients.

“These new data add clarity to the risk-to-benefit ratios of actively managing the broad spectrum of patients with severe AS, but they also have potential implications for those patients with less severe forms of AS,” Strange et al. wrote in JACC. “Although there is both historical and contemporary evidence to suggest that mild to moderate forms of AS are not as benign as commonly assumed, particularly in the presence of concurrent systolic dysfunction, nearly all relevant studies have had limited numbers of patients and/or short-term follow-up.”

Strange and his team leveraged data from the National Echocardiographic Database of Australia (NEDA) for their study, allowing them the capacity to individually link echocardiographic findings with long-term mortality in a large, unselected patient population. Measuring aortic valve (AV) mean gradient, peak velocity and area, the researchers characterized the severity of AS in 122,809 male patients and 118,494 female patients.

After following up with participants for an average of 1,208 days, Strange and colleagues reported that 6.7% of the pool had mild AS, 1.4% presented with moderate AS and 2.6% had severe AS. Compared to patients without AS, those with mild to severe forms of the disease saw between a 44% and 2-fold increased risk of long-term mortality.

Five-year mortality was 56% in patients with moderate AS and 67% in those with severe AS, the authors said, corresponding to AV mean gradients of between 20 and 39 mmHg and 40 mmHg or higher, respectively. Peak velocity for patients with moderate AS hovered between 3 and 3.9 m/s; in patients with severe AS peak velocity exceeded 4 m/s.

Strange and co-authors wrote that a “markedly increased” risk of death from all causes and CVD was apparent from a population mean AV gradient of greater than 20 mmHg—a number that stayed steady even after adjusting for age, sex, LV systolic or diastolic dysfunction and aortic regurgitation.

Mani A. Vannan, MBBS, of the Piedmont Heart Institute in Atlanta, and co-authors said in a related editorial comment that the team’s finding that mortality rates for both moderate and severe AS were similar was the most intriguing result of the study. It suggests moderate AS is not, in fact, a benign stage in the evolution of disease and underscores the importance of timely intervention.

“These data may prompt reconsideration of the current time-honored approach of classifying AS as mild, moderate and severe using Doppler echocardiographic data,” Vannan et al. wrote. “This approach by its nature implies that the assessment of the degree of AS is relevant to that single point of assessment of the valve and that Doppler hemodynamics are by themselves not sufficient to fully characterize the disease severity.”

The editorialists said the challenge moving forward will be considering a “less dogmatic approach” to AS classification rather than relying solely on valve hemodynamics.

“The complete characterization of AS includes disease severity, progression and management, the emphasis being the disease, not just the valve,” they wrote. “TAVR is a groundbreaking advance in the treatment of AS, which is now applicable to patients with severe AS at low risk for surgery. Therefore, it behooves us to open our eyes, ears and minds and continue to make strides in the effective and timely management of the significant public health problem that is AS.”