Early Valve Replacement in Asymptomatic Severe Aortic Stenosis: New Support

October 10, 2018

A cohort study supports early referral for aortic-valve replacement (AVR) in asymptomatic patients with severe aortic stenosis who have at least one of two echocardiographic signs of increased risk.

Demonstration of a peak aortic-valve jet velocity of 5 m/s or greater in such patients predicted all-cause and cardiovascular (CV) mortality both before and after successful AVR in a retrospective look at patients managed from 2001 to 2014.

A left-ventricular ejection fraction (LVEF) less than 60% also predicted pre-AVR all-cause and CV mortality, as well as post-AVR all-cause mortality, in the study of participants in an international registry who were followed at dedicated heart-valve clinics.

The findings, published online October 3 in JAMA Cardiology, support raising the traditional less than 50% LVEF threshold for defining left-ventricular (LV) dysfunction and consideration of AVR in such patients to less than 60%, researchers say.

"The two parameters," a peak aortic-valve jet velocity of at least 5 m/s and LVEF less than 60% at study entry, "alone or even better when they were combined, were associated with a worse outcome in terms of overall survival and cardiovascular mortality, even after surgery or TAVR," lead author Patrizio Lancellotti, MD, PhD, observed for the theheart.org | Medscape Cardiology.

Symptomatic severe aortic stenosis with low LVEF is a class I indication for AVR, but guidelines give a class IIa indication in the absence of symptoms, observed Lancellotti, of University of Liège Hospital and Centre Hospitalier Universitaire du Sart Tilman, Belgium.

For asymptomatics with the echo risk markers, he said, "We think it should be a class I recommendation" that such patients be considered for surgical or transcatheter AVR (TAVR).

The 1375 patients with moderate to severe aortic stenosis in the current analysis, followed at 10 heart-valve clinics in Canada, Europe, and the United States, were part of the prospective Heart Valve Clinic International Database (HAVEC). Severe aortic stenosis was defined as an aortic-valve area less than 1.0 cm2.

During medical management across the entire cohort, 2-year survival was 93%; survival was 86% at 4 years and 75% at 8 years. Seven of the 57 CV deaths were sudden cardiac death (SCD).

Of the 861 patients who entered the study with severe aortic stenosis, 32 died of CV causes during medical-only management, including four from SCD.

"The findings from this international patient database generally confirm the low incidence of sudden cardiac death among asymptomatic patients with aortic stenosis," and are in line with other reports, notes an accompanying editorial by Patrick T. O'Gara, MD, Brigham and Women's Hospital, Boston, Massachusetts, and Robert O. Bonow, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

O'Gara and Bonow emphasize the findings that peak aortic jet velocity of at least 5 m/s and LVEF below 60% predicted mortality, "even following AVR. If validated in other studies, these observations could influence decision-making and the timing of surgical referral," they write.

The current analysis is probably the first to demonstrate the Doppler and two-dimensional echo measures as mortality predictors in a large cohort of asymptomatic patients with aortic stenosis who were "regularly followed up at dedicated valvular heart disease centers," Lancellotti said.

In the patients initially with severe aortic stenosis, independent predictors of all-cause mortality, the study's primary endpoint, included age (P = .001), systolic blood pressure (P = .003), chronic obstructive pulmonary disease (P = .02), peak aortic jet velocity of at least 5 m/s (P = .046), and LVEF less than 60% (P < .001). The latter two features, along with age and diabetes, significantly predicted CV death, a secondary endpoint.

Surgical AVR or TAVR was performed in 542 patients, or about 39% of the cohort. Of those who underwent the procedure, about 72% had entered the study with severe aortic stenosis and 28% entered with moderate aortic stenosis.

About 45% of patients initially with severe aortic stenosis underwent AVR of either form, mostly surgical, after a mean of 14.4 months from study entry (median 8.7 months).

 

Survival Rates After AVR for Patients Initially With Severe Aortic Stenosis, by Peak Aortic Velocity (P = .03) and Baseline LVEF (P = .02)

Follow-up Peak Aortic Jet Velocity, m/s   Baseline LVEF, %
  ≥ 5 < 5 < 60 ≥ 60
2 years 73 84 67 87
4 years 65 78 63 78
6 years 54 70 63 69

 

Across all patients undergoing AVR, multivariate predictors of post-AVR survival did not include LVEF less than 60%, but did include the following:

  • Age (HR, 1.03; 95% CI, 1.01 - 1.06; P = .003)

  • Diabetes (HR, 2.62; 95% CI, 1.90 - 4.95; P = .003)

  • Dyslipidemia (HR, 0.2; 95% CI, 0.10 - 0.37; P < .001)

  • Peak aortic velocity > 5 m/s (HR, 2.20; 95% CI, 1.16 - 4.18; P = .02)

Based on the current findings, Lancellotti said, asymptomatic patients with severe aortic stenosis should be evaluated by a heart team for possible intervention when their peak aortic jet velocity reaches 5 m/s or LVEF goes below 60%. "And if they are not referred for any kind of intervention, they should be followed up very carefully."

That means active surveillance with scheduled echocardiography and clinical evaluation, "not watchful waiting," he said.

O'Gara and Bonow point to the ongoing Early Transcatheter Aortic Valve Replacement (EARLY TAVR) trial, now in its early stages, which expects to randomize about 1100 asymptomatic patients similar to those in the current analysis to TAVR or active surveillance.

The primary endpoint of the trial sponsored by Edwards Lifesciences is death by any cause, stroke, or unplanned CV hospitalization. It's expected to have results in about 3 years.

Lancellotti has reported no relevant financial relationships.  Disclosures for the other authors are in the report. Both O'Gara and Bonow have reported no relevant financial relationships .

JAMA Cardiology. Published online October 3, 2018. Abstract, Editorial

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