By Michael H. Crawford, MD, Editor

SYNOPSIS: A retrospective observational study of the incremental value of echocardiographic global longitudinal strain (GLS) for predicting mortality in asymptomatic patients with moderate to severe aortic regurgitation and normal left ventricular function showed that GLS was a predictor of mortality. However, GLS was not as robust as undergoing surgery was for predicting mortality.

SOURCES: Alashi A, Mentias A, Abdallah A, et al. Incremental prognostic utility of left ventricular global longitudinal strain in asymptomatic patients with significant chronic aortic regurgitation and preserved left ventricular ejection fraction. JACC Cardiovasc Imaging 2018;11:673-682.

Cavalcante JL. Global longitudinal strain in asymptomatic chronic aortic regurgitation: The missing piece for the watchful waiting puzzle? JACC Cardiovasc Imaging 2018;11:683-685.

The timing of surgical intervention in patients with chronic valvular aortic regurgitation (AR) remains challenging. Investigators from the Cleveland Clinic performed a retrospective observational study to evaluate the incremental value of left ventricular (LV) global longitudinal strain (GLS) by speckle tracking echocardiography for predicting mortality in asymptomatic patients with 3+ or 4+ chronic AR, preserved LV ejection fraction > 50%, and LV end-systolic dimension index < 2.5 cm/m². Excluded were patients with other valve or other heart diseases, previous heart surgery, or aortic dissection. AR severity was established based on several echocardiographic measurements. The primary outcome was all-cause mortality during follow-up. The average age of patients was 53 years, and 77% were men.

At baseline, the median GLS was -19.5%, with 52% better than the median, and 48% worse. Surgery was performed on 63% at a median of 42 days from baseline. During the seven-year follow-up, 14% died, almost all of a cardiac cause. A higher proportion of patients with GLS worse than the median died compared to those better than median (17% vs. 11%; P = 0.01). The risk of death at five years increased significantly with GLS worse than -19%. A multivariate hazard analysis revealed several measures predictive of mortality: surgical risk score, LV end-systolic dimension index, GLS, right ventricular (RV) systolic pressure, and aortic valve surgery (favorable). The C-statistic for the clinical variables of surgical risk score, LV end-systolic dimension index, and RV pressure was 0.61. Sequentially adding GLS and surgery increased the C-statistics to 0.67 and 0.77, respectively. Among those not undergoing surgery, all deaths occurred in patients who did not meet current criteria for surgery. The authors concluded that GLS provides incremental prognostic value in asymptomatic patients with chronic AR who do not meet current criteria for surgery.

COMMENTARY

Current guidelines recommend aortic valve replacement surgery in patients with severe AR if they are symptomatic or exhibit evidence of LV dysfunction manifested as an ejection fraction < 50% (class I) or an end-systolic dimension index > 5 cm (> 2.5cm/m²; class II a), or EDD > 6.5 cm (class II b). These guidelines are largely based on observational studies from 30 years ago. Many clinicians believe that they are based on the point when valve replacement usually is not successful in restoring LV function. Accordingly, there has been a movement to operate somewhat earlier, but the decision points for earlier surgery are unclear. In this study, 3+ or 4+ AR events was considered enough to qualify for surgery. Although not delineated in the study, presumably, this is based on a four-point scale, where 1+ is mild, 2+ is mild to moderate, 3+ is moderate to severe, and 4+ is severe. In this study, and most other recent studies, AR severity is based on a combination of echo measures that are never precisely described, as not all measures are available in all patients.

The first point this paper makes is that the current cutpoint for end-systolic dimension index > 2.5cm/m² is probably too high. Among patients who did not undergo surgery, 84% of the deaths occurred in patients with an end-systolic dimension index < 2.0 cm/m². Also, LV ejection fraction didn’t make the cut in the multivariate analysis. One issue here is that the lower limit of ejection fraction by echo is now 55%, according to the American Society of Echocardiography. Perhaps < 55% by echo would be a better criterion.

Several new measures have been advanced as potential replacements or additional criteria for surgery, including exercise testing, LV torsion, brain natriuretic peptide levels, MRI for fibrosis, and GLS. Alashi et al assessed GLS, which was obtainable in > 90% of their patients and showed that values worse than the median add prognostic information for mortality. However, choosing surgery was the best predictor of survival, which complicates this analysis. Clearly, this retrospective observational study suffers from selection bias, so it can only be hypothesis-generating. Also, GLS was only measured once at baseline. Serial measurements may have carried additional value, but as echo experts know, such measurements would have to be obtained from the same machines as there is not an industry standard for GLS. If cardiologists have access to GLS, they probably should start measuring it in chronic AR patients, as it may bolster the decision-making. However, GLS is not ready to be an independent criteria for surgery at this time.