Global Longitudinal Strain May Help Predict Need for Early Intervention in Asymptomatic Severe AS

Worsening LV global longitudinal strain may be a harbinger of the need for intervention in patients with asymptomatic severe aortic stenosis (AS) and normal ejection fraction, new research hints. In a multicenter registry, patients with evidence of strain on echocardiography had increased risk of developing symptoms and requiring surgical or transcatheter aortic valve interventions over time.

Study co-author Philippe Généreux, MD (Morristown Medical Center, NJ), said in an interview with TCTMD that the findings suggest that there is a better way than LV ejection fraction alone to quantify cardiac damage caused by aortic stenosis before clinical symptoms develop. This could potentially help identify patients who could benefit from earlier intervention, he said.

“Strain is a reflection of the consequence of the overdose of pressure over time,” he said. “It allows us to see an early manifestation of that overload of pressure from the aortic stenosis on the ventricle.”

As patients in the study progressively developed symptoms, their LV global longitudinal strain measures further deteriorated despite no change in their LV ejection fraction. While assessing for strain is a bit more challenging than reading a standard echo, Généreux said the argument can be made that it may ultimately become a routine part of management for asymptomatic AS patients if its value in prognosis can be fully illustrated.

Commenting on the study, Ted Feldman, MD (Evanston Hospital, Chicago, IL), said he was not surprised to see that patients with less favorable strain numbers developed more symptoms.

"One of the things that happens to the left ventricle when it lives with aortic stenosis for a long time is increasing amounts of fibrosis,” Feldman said. “And that's what I think we all assume is the explanation for this finding.” He noted that symptomatic or more severe AS patients may have a spectrum of degrees of fibrosis.

"Strain might do a good job of helping define that spectrum and its prognostic importance," he added.

The More Things Strain, the Less They Stay the Same?

The registry-based study of patients from the Netherlands, Belgium, and Canada led by E. Mara Vollema, MD (Leiden University Medical Center, the Netherlands), was published online August 15, 2018, ahead of print in JAMA Cardiology. It looked at retrospective data from 220 asymptomatic AS patients with normal LV ejection fraction and a similar number of controls with no structural heart disease. All underwent transthoracic echocardiography with speckle tracking analysis on apical two-, three-, and four- chamber views using commercially available software.

Compared with controls, the asymptomatic AS patients showed significant impairment of LV global longitudinal strain. On average, 70% of asymptomatic patients had impaired strain with no variation in percentage or mean LV global longitudinal strain measures across the three centers where patients were treated, and little in the way of differences between measurements taken across different imaging platforms.

In a subgroup of 150 patients with echocardiograms taken a median of 12 months apart, mean transvalvular gradients and LV mass index increased significantly and aortic valve area decreased. LV ejection fraction, however, remained unchanged. Mean LV global longitudinal strain in these patients worsened over time, suggesting the presence of subclinical LV dysfunction.

Overall, 54% of the 220 patients with asymptomatic severe aortic stenosis developed symptoms over a median follow-up of 12 months, with 74% of them subsequently undergoing surgical or transcatheter AVR.

The researchers further evaluated the prognostic value of LV global longitudinal strain by dividing patients into groups of more impaired or more preserved baseline values. Patients with more impaired values had higher cumulative rates of symptom development over time than those with more preserved values. Additionally, compared with patients with more preserved measures of strain, those with more impaired levels had more CAD (30% vs 15%; P = 0.01) and more A-fib (26% vs 12%; P = 0.01). Echocardiography showed that patients with more impaired strain also had a larger LV mass index and lower ejection fraction than patients with more preserved strain, even though both groups had LV ejection fraction > 60%.

Potential Clinical Implications

In an editorial accompanying the study, James D. Thomas, MD (Northwestern University, Chicago, IL), notes that over the last decade LV global longitudinal strain has emerged as a more reliable predictor of outcomes than ejection fraction in other clinical scenarios such as acute heart failure and mitral regurgitation.

However, with regard to AS patients, it is “difficult to know which value of global longitudinal strain should cause concern, as [the authors] had a generous definition for abnormality . . . ,” he says.

To TCTMD, Feldman said the study, coupled with ongoing research efforts into strain values and their prognostic importance, has wide-ranging clinical implications.

"Currently these patients are followed with clinic visits every few months, but I suppose if I saw one of these patients who had completely normal strain values it would help with the conversation with that patient, and it also might help me decide if I want to see them in 6 months or 4 months," he said.

Feldman also said it will be "fascinating" to explore changes in strain values measured before and after TAVR as is currently being done in the EARLY-TAVR trial.

According to Thomas, it also may be time for randomized trials of patients with asymptomatic severe AS to evaluate AVR decisions based on care guided in part by global longitudinal strain values versus current guidelines.

If successfully completed, Thomas says “such a trial would inform the next edition of the valve guidelines to use measures of left ventricular function that were developed more recently than 50 years ago to guide the timing of intervention in AS.”

Généreux agreed. “It remains to be demonstrated, but our findings support the notion that earlier intervention, or at least earlier detection of the consequences of AS that are not visible clinically or with simple metrics of echo, has value,” he concluded.

Note: Study co-author Martin B. Leon, MD, is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.