Treadmill Stress Echo Appears to Help Guide Care of Asymptomatic or Atypical Mitral Stenosis

Future guidelines for managing patients with mitral stenosis who are asymptomatic or have atypical symptoms might be improved by incorporating treadmill stress echocardiography results. So suggests a newly published article in Circulation: Cardiovascular Imaging (2019;12:e009062) reporting on an observational cohort study of more than 500 patients with suspected significant mitral stenosis managed at Cleveland Clinic over a recent 11-year period.

Greater mortality was found to be associated with primary nonrheumatic mitral stenosis, lower age- and sex-predicted exercise capacity, and higher peak-stress right ventricular systolic pressure (RVSP), whereas invasive mitral valve procedures were associated with better survival.

“The management of patients with native nonrheumatic mitral stenosis or following mitral valve surgery is controversial and becoming a proportionately larger issue now that we see rheumatic heart disease much less often,” says Milind Desai, MD, corresponding author of the study report and Professor of Medicine at Cleveland Clinic Lerner College of Medicine. “Our analysis indicates that stress echocardiography may offer important prognostic information to help guide management in a variety of patients with mitral stenosis who are asymptomatic or have atypical symptoms.”

Study design and population features

The study included 515 consecutive Cleveland Clinic patients with suspected significant MS (based on valvular parameters) who underwent resting and treadmill stress echocardiography as part of a comprehensive evaluation between January 2003 and December 2013. All were either asymptomatic or had atypical symptoms not deemed to be caused by valvular heart disease. Patients were excluded if there had not been a clinical reason to perform stress echo or if they had left ventricular ejection fraction less than 55%, hypertrophic cardiomyopathy or a subaortic membrane.

The study population’s mitral stenosis was categorized as follows:

• Rheumatic (n = 170, 33%)
• Postsurgical (i.e., prior mitral repair or replacement) (n = 245, 48%)
• Primary nonrheumatic (n = 100, 19%)

Overall, 224 patients (44%) underwent an invasive mitral valve procedure, at a median of 54 days after treadmill testing. Across the cohort, 76 deaths (15%) occurred over mean follow-up of 6 + 4 years; 64 of these were due to cardiac causes.

Echocardiograms from a patient with mitral stenosis before (top) and after (bottom) surgical intervention.

Results yield prognostic insights

Survival analysis revealed that higher long-term mortality was significantly associated with the following:

• Primary nonrheumatic mitral stenosis: hazard ratio (HR) = 4.92; 95% confidence interval (CI), 2.78-8.71
• Higher Society of Thoracic Surgeons score (for every 1% increase in absolute risk): HR = 1.92 (1.84-1.99)
• Lower exercise capacity (for every 10% decrease in age- and sex-predicted metabolic equivalents [METs] achieved): HR = 1.22 (1.11-1.35)
• Higher peak-stress RVSP (for every 10-mmHg increase): HR = 1.35 (1.13-1.62)

Spline analysis showed that thresholds of peak-stress RVSP of at least 60 mmHg and achieved age- and sex-predicted METs of less than 85% were associated with increased long-term mortality.

In addition, invasive mitral valve procedures (valvuloplasty or repair/replacement) were associated with significantly lower mortality (HR = 0.67 [0.55-0.81]).

Study contributions and limitations

According to the authors, this study is one of the largest to characterize mitral stenosis in the developed world in the modern era and to assess prognosis using echocardiographic and exercise factors. Comparable studies have focused largely on patients with rheumatic mitral stenosis.

“Our findings suggest a role for exercise echocardiography in helping to determine appropriate surgical timing in patients with mitral stenosis who have no symptoms or atypical symptoms,” says co-author A. Marc Gillinov, MD, Cleveland Clinic’s Chair of Thoracic and Cardiovascular Surgery. “Relying solely on patients’ perception of their symptoms can underestimate both the severity of mitral stenosis and the risk of death.”

He adds that although the study identified specific stress performance thresholds that generated significantly different survival curves, it would be premature to recommend these thresholds as criteria for intervention. Although the study was large, it was limited by its observational, single-center nature. The study authors encourage validation of the findings in a multicenter study, preferably with a prospective design.

An accompanying editorial by two clinicians at Morristown Medical Center in New Jersey also argues for more study. The editorialists call the study “an important addition to the evidence base for stress echocardiography in mitral stenosis” that complements prior studies limited to rheumatic mitral stenosis. They conclude that it “provides data supporting but not proving the hypothesis that stress echocardiography results should influence clinical decision-making.”