Survival Better With Early AVR for Severe Asymptomatic Aortic Stenosis, Says Retrospective Study
While there may be a safe window for watchful waiting, randomized data are needed to shed more light on the timing, experts advise.
Waiting for symptoms to emerge before intervening with surgical valve replacement in asymptomatic patients with severe aortic stenosis (AS) increases the risk of death, new research shows. Patients recommended for surgical aortic valve replacement (AVR) at this early stage show a clear survival advantage by 2 years compared with those for whom a surveillance strategy was recommended.
Senior author S. Chris Malaisrie, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), said the data add to a growing body of literature supporting early treatment for patients with severe stenosis but no symptoms.
“It seems that patients are probably okay for up to a year without treatment,” he said in an interview with TCTMD. “But survival starts to separate after 1 year.”
Philippe Généreux, MD (Morristown Medical Center, NJ), who commented on the study for TCTMD agreed that there probably is an acceptable waiting period for this patient population, although exactly how long that period is remains unclear. But he added that the retrospective nature of the current study makes it unlikely that there was equipoise between the two groups.
“We know that patients who undergo AVR are most likely in better shape and are perceived as being able to tolerate an invasive surgery compared with those not treated early,” he said. “Only a prospective trial with good randomization will definitely be able to answer the question of optimal timing of the intervention.”
Understanding Watchful Waiting
Généreux is the principal investigator for EARLY TAVR, which is currently enrolling and hopes to have a good shot at finally answering some of the outstanding questions surrounding the optimal of severe, asymptomatic AS, albeit using TAVR, not surgery. Patients in the trial are being randomized to watchful waiting or early TAVR. Both PARTNER 3 and the Evolut TAVR in Low-Risk Patients trial have recently shown that TAVR is noninferior to surgery in low-risk patients, with even better results than investigators had hoped.
Généreux added that EARLY TAVR also will help physicians understand what constitutes adequate watchful waiting, so that they do not miss the window of opportunity to intervene before symptoms occur.
Malaisrie agreed that better surveillance and understanding of that window is needed.
“I think every doctor who treats these patients is uncomfortable leaving severe disease alone,” he said. “We tell the patient you really have to come back in 6 months so we can look for early signs of heart failure, but sometimes patients go away and then the next time you see them they're in the hospital with heart failure because they haven't been followed closely.” He added that while protocols for this type of follow-up require optimization, another important part of the equation is the communication between physicians and patients about the seriousness of the situation so the follow-up is not forgotten or dismissed.
The study, published online March 21, 2019, ahead of print in the Annals of Thoracic Surgery, and led by Malaisrie’s colleague John Campo, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), examined the medical records of 265 asymptomatic AS patients who presented at their institution from 2005 through 2013, and in whom early surgical AVR (n = 104) or watchful waiting (n = 161) was recommended. Patients in the AVR group tended to be younger, have smaller aortic valve areas, higher Vmax, and higher mean gradient on echocardiogram than those in the watchful waiting group. Most of those assigned to the AVR group underwent the surgery (93%), as did nearly half of the watchful waiting patients (47%).
At 1 year, the difference in all-cause mortality between the two groups was not statistically significant. However, 2-year mortality was significantly higher for the watchful waiting group compared with early AVR (16.1% vs 7.5%; P = 0.044), as was 3-year mortality (21.1% vs 9.0%; P = 0.011). Among the watchful waiting group, those who underwent surgical AVR had better overall survival than those who did not.
For the entire study cohort, older age and renal failure were associated with poorer survival, while higher ejection fraction was predictive of lower mortality risk.
Underuse of Stress Tests Problematic
To TCTMD, Malaisrie said one surprising finding of his study was the low use of stress testing (18% in the early AVR group and 37% in the watchful waiting group).
“It’s a very useful tool because patients will often say they are asymptomatic, but when you actually put them on the treadmill you have to stop the test because they have chest pain,” he explained. “Even at our site I think we are probably underutilizing stress testing to stratify our asymptomatic patients.”
Some of the reasons for the low rates may be related to unfounded fears on the part of clinicians about stressing older, sick patients, Malaisrie added.
“If the stress test is negative this is where we think there is probably an equipoise between watchful waiting an early intervention,” Généreux noted. “That is the group where we really don’t know what to do.”
In the time since their retrospective study was completed, Malaisrie said his group has begun actively enrolling patients in the EARLY TAVR trial. This has increased their use of stress testing, he added, since it is a requirement of the study protocol to attempt the test unless there is a valid clinical reason not to do it.
By having as close to a true no-symptom population as possible, EARLY TAVR may help clinicians to better gauge whether a patient will develop symptoms slowly, meaning that they have time to report to their doctor before cardiac damage occurs, or whether they will “crash and burn acutely and we miss the opportunity to perform AVR while they are in stable condition,” Généreux said. “Is there a price to wait? I think everybody is now convinced that with TAVR being less invasive, bearing a lower mortality and stroke rate than surgery, it’s even much more appealing to offer early intervention to asymptomatic patients compared to surgery because the initial hit is less.”
Campo J, Tsoris A, Kruse J, et al. Prognosis of severe asymptomatic aortic stenosis with and without surgery. Ann Thorac Surg. 2019;Epub ahead of print.
Généreux reports consulting and proctoring for Edwards Lifesciences and serving as the national principal investigator for EARLY TAVR.
- Campo and Malaisrie report no relevant conflicts of interest.