When does asymptomatic aortic stenosis warrant surgery? Assessment techniques
ABSTRACTAsymptomatic but hemodynamically severe aortic stenosis often poses a dilemma: should the aortic valve be replaced, or is watchful waiting acceptable? Patients with this condition are a diverse group with varying prognoses. Here, we review the guidelines for valve replacement in this situation and highlight the variables useful in establishing which patients should be considered for early intervention even if they have no symptoms.
KEY POINTS
- Echocardiography is the best established and most important initial test in patients with suspected aortic stenosis.
- Traditional echocardiographic variables used in assessing aortic stenosis and the need for surgery are the pressure gradient across the valve, the velocity through the valve, the valve area, and the left ventricular ejection fraction.
- Aortic valve replacement is recommended for severe aortic stenosis if the patient has symptoms. It is also recommended if the left ventricular ejection fraction is less than 50%, if the patient is undergoing other cardiac surgery, or if symptoms arise on exercise stress testing.
- Novel assessment variables include left ventricular hypertrophy, left atrial size, B-type natriuretic peptide level, and global left ventricular longitudinal strain.
Left ventricular hypertrophy
The development of left ventricular hypertrophy is one of the earliest compensatory responses of the ventricle to the increase in afterload. This leads to impaired myocardial relaxation and reduced myocardial compliance, with resultant diastolic dysfunction with increased filling pressures.
Cioffi et al,27 in a study in 209 patients with severe but asymptomatic aortic stenosis, found that inappropriately high left ventricular mass (> 110% of that expected for body size, sex, and wall stress) portended a 4.5-times higher risk of death, independent of other risk factors.
Severe left ventricular hypertrophy may have a long-term effect on prognosis irrespective of valve replacement. An observational study14 of 3,049 patients who underwent aortic valve replacement for severe aortic stenosis showed that the 10-year survival rate was 45% in those whose left ventricular mass was greater than 185 g/m2, compared with 65% in patients whose left ventricular mass was less than 100 g/m2.
Thus, as surgical mortality and morbidity rates decrease, the impact of these structural changes in left ventricular wall thickness may affect the decision to intervene earlier in order to improve longer-term outcomes in select asymptomatic patients with high-risk features.
Left atrial size
Diastolic dysfunction is caused by increased afterload and results in elevated left ventricular end-diastolic pressure and elevated left atrial pressure. The left atrium responds by dilating, which increases the risk of atrial fibrillation.
Lancellotti et al8 investigated the negative prognostic implications of a large indexed left atrial area in asymptomatic patients with severe aortic stenosis. They found that patients with an indexed left atrial area greater than 12.2 cm2/m2 had a 77% 2-year probability of aortic valve replacement or death.
Beach et al28 examined cardiac remodeling after surgery and found that the left atrial diameter did not decrease after aortic valve replacement, even after left ventricular hypertrophy reversed. This observation has major prognostic implications. Patients with a severely enlarged left atrium (> 5.0 cm in diameter) had considerably lower survival rates than patients with a diameter less than 3.55 cm at 5 years (61% vs 85%) and at 10 years (28% vs 62%) after aortic valve replacement.
Therefore, left atrial size appears to have an important long-term impact on prognosis in patients with aortic stenosis even after aortic valve replacement and adds valuable information when assessing the effect of aortic stenosis on myocardial function.
B-type natriuretic peptide
Natriuretic peptides are cardiac hormones released in response to myocyte stretch. In aortic stenosis, increased afterload induces significant expression of BNP, N-terminal proBNP,29 and atrial natriuretic peptide,30 with numerous studies showing a good correlation between plasma natriuretic peptide levels and severity of aortic stenosis.31–34
Bergler-Klein et al33 showed that patients with asymptomatic aortic stenosis who developed symptoms during follow-up had higher levels of these biomarkers than patients who remained asymptomatic. Of note, patients with BNP levels lower than 130 pg/mL had significantly better symptom-free survival than those with higher levels, 66% vs 34% at 12 months.
However, these biomarkers are not specific to aortic stenosis and can be elevated in any condition that increases left ventricular stress. Nevertheless, they offer an easy and low-cost way to assess left ventricular function and may give an indication of the total burden of disease on the left ventricle.
Global left ventricular longitudinal strain
In view of the limitations of the left ventricular ejection fraction in identifying changes in the structure of the heart and in early detection of myocardial dysfunction, assessment of myocardial deformation using strain imaging is proving an attractive alternative.
Strain is the normalized, dimensionless measure of deformation of a solid object (such as a segment of myocardium) in response to an applied force or stress.35 A novel echocardiographic technique allows assessment of segmental myocardial deformation and thereby overcomes the limitation of tethering, which limits other echocardiographic techniques in the assessment of systolic function. Strain can be circumferential, longitudinal, or radial and is generally assessed using either tissue Doppler velocities or 2D echocardiographic speckle-tracking techniques. Longitudinal strain has proven to be a more sensitive method than left ventricular ejection fraction in detecting subclinical myocardial dysfunction and is a superior prognosticator in a variety of clinical conditions.36,37
Abnormal strain develops very early in the disease process and can even be seen in patients with mild aortic stenosis.
A study by Kearney et al38 in 146 patients with various degrees of aortic stenosis (26% mild, 21% moderate, and 53% severe) and preserved left ventricular ejection fraction demonstrated that global longitudinal strain worsened with increasing severity of aortic stenosis. Furthermore, global longitudinal strain was a strong independent predictor of all-cause mortality (hazard ratio 1.38, P < .001).
Similarly, in a study by Lancellotti et al8 in 163 patients with at least moderate to severe asymptomatic aortic stenosis, impaired longitudinal myocardial strain was an independent predictor of survival. Patients with longitudinal strain greater than 15.9% had significantly better outcomes than patients with strain of 15.9% or less (4-year survival 63% vs 22%, P < .001).
Hence, left ventricular global longitudinal strain offers an alternative—perhaps a superior alternative—to left ventricular ejection fraction in detecting and quantifying left ventricular dysfunction in asymptomatic aortic stenosis. It is an exciting new marker for the future in aortic stenosis, with a threshold of strain below 15.9% as a possible cutoff for those at higher risk of poorer outcomes.
WHERE ARE WE NOW? WHERE ARE WE GOING?
Aortic valve replacement in patients with severe but asymptomatic aortic stenosis remains a topic of debate, but support is growing for earlier intervention.
Now that concerns over the safety of exercise stress testing in patients with severe asymptomatic aortic stenosis have subsided following multiple studies,16,17 exercise testing should be performed in patients with asymptomatic severe aortic stenosis suspected of having reduced exercise capacity, with stress echocardiography providing added prognostic information through its assessment of exercise-induced changes in mean pressure gradient19 and systolic pulmonary artery pressure.21–23
Assessing left ventricular function provides important information about prognosis, with left ventricular ejection fraction, left ventricular diameter, left atrial size, BNP, and global longitudinal strain all helping identify asymptomatic patients at higher risk of death. Surgical intervention in asymptomatic patients with severe aortic stenosis may be considered when there is evidence of higher longer-term mortality risk based on reduced functional capacity, excess left ventricular hypertrophy, and abnormal left ventricular function as detected by ancillary methods such as global longitudinal strain and BNP elevation despite a normal left ventricular ejection fraction.
Figure 3 shows a possible algorithm to define which patients would benefit from earlier intervention. However, left ventricular hypertrophy, left atrial diameter, BNP, left ventricular longitudinal strain, and changes in systolic pulmonary artery pressure are not included in the current ACC/AHA guidelines for the management of asymptomatic patients with severe aortic stenosis. Further study is needed to determine whether earlier intervention in those with adverse risk profiles based on the newer evaluation techniques described above leads to better long-term outcomes.
Intervention should especially be considered in those in whom the measured surgical risk is low and in surgical centers at which the mortality rate is low.
