In patients with left ventricular (LV) pressure overload from aortic stenosis (AS), there is a close relationship among LV function, flow, and transvalvular gradients. The association between a low gradient and low flow (reduced stroke volume or cardiac output) has long been recognized and is highlighted in the Gorlin formula, but this has traditionally been considered relevant only in the setting of overt LV dysfunction with a decreased ejection fraction (EF). However, the limitations of EF as an accurate measure of LV systolic function in patients with pressure overload and hypertrophic LV remodeling from AS have been described. Chamber volume and contractile function both influence LV “pump” function and, accordingly, the stroke volume generated.
In 2007, Hachicha et al . first described a group of patients with paradoxical low-flow, low-gradient severe AS. These patients are characterized by an indexed aortic valve area < 0.6 cm 2 /m 2 , stroke volume index < 35 mL/m 2 , mean transvalvular gradient < 40 mm Hg, and EF ≥ 50%. Since then, several studies have demonstrated that despite the calculated gradient, which suggests only moderate disease, these patients actually do have advanced disease and hemodynamically severe stenosis. It is important to note that these patients have a better prognosis with transcatheter or surgical valve replacement compared with medical therapy. Flow, in fact, is emerging as a better predictor of clinical outcomes than EF.
In patients with AS, flow is affected by multiple factors; principal among them are LV pump function (influenced mostly by contractile function and chamber volumes) and LV afterload. Although the valvular contribution to LV afterload in patients with AS is self-evident, it is also important to recognize the contribution of vascular afterload to total LV afterload in these patients. Afterload is not “fixed” (i.e., not due entirely to the valve) in patients with AS. Indeed, increased vascular and global LV afterload are associated with lower stroke volume index and impaired myocardial function. Acute reduction in systemic vascular load (decreased systemic vascular resistance and increased systemic arterial compliance) is associated with increased flow in patients with severe symptomatic AS.
Given the emerging role of stroke volume index as an integrative surrogate of the balance of LV afterload and LV pump function and as a predictor of clinical outcomes, is there a role for more sensitive, quantitative measures of LV mechanics and function to improve clinical management and treatment decisions in patients with AS?
Left Ventricular Mechanics and Aortic Stenosis
The motion of the heart occurs in multiple directions during contraction, and myocardial strain assessment has been helpful in elucidating this complicated and coordinated systolic motion in a variety of cardiovascular diseases, including AS. In patients with pressure overload from AS, some studies have identified abnormalities in radial, circumferential, and longitudinal strain and strain rate compared with normal controls, whereas other studies have found abnormalities only in longitudinal strain. Moreover, there is evidence that the twisting motion of the heart, particularly in the apex, is increased in AS. This may be a compensatory mechanism to maintain cardiac output in the face of pressure overload; the loss of this compensatory increase in LV twist may precede clinical decompensation.
Among indices of LV mechanics studied in AS, longitudinal strain has been most commonly evaluated and is frequently abnormal in patients with AS, particularly in the basal segments. Longitudinal strain provides a more sensitive index of LV systolic function than EF and is influenced by LV afterload (valvular and vascular), hypertrophic remodeling, and chamber dimensions. There is also accumulating evidence for a relationship between impaired longitudinal strain and the presence and extent of myocardial fibrosis.
In several studies, impaired longitudinal strain has been associated with increased rates of mortality and major adverse cardiac events in patients with AS. This adverse relationship is maintained even after adjustment for EF and other clinical and echocardiographic factors associated with mortality. In patients with asymptomatic severe AS, reduced longitudinal strain has been associated with abnormal exercise test results and more cardiac events in follow-up.
To date, a few studies have evaluated the change in LV mechanics after surgical or transcatheter aortic valve replacement. In this issue of JASE , Kamperidis et al . provide new insights into the change in LV mechanics, specifically longitudinal strain, and hypertrophic remodeling after transcatheter aortic valve implantation (TAVI). They focus on the subgroup of patients with low-flow, low-gradient severe AS with either reduced (<50%) or preserved (≥50%) EF. Given that this group of patients is higher risk with more advanced LV dysfunction, it is important to evaluate whether LV function improves in these patients after TAVI. Consistent with prior studies, they report that approximately half of the patients with low-flow, low-gradient AS had preserved EF. They confirmed the increased sensitivity of longitudinal strain to identify “subclinical” LV dysfunction in that those with preserved EF at baseline had a mean EF of 61 ± 6% but abnormal global longitudinal strain (−13.1 ± 3.5%). Accordingly, longitudinal strain assessment was able to identify improvements after TAVI in global and basal longitudinal strain and global strain rate in those with preserved EF but abnormal strain at baseline, whereas there was no significant change in EF in this group. In those with low EF at baseline, improvement in LV function after TAVI was evidenced by improvement in both EF and longitudinal strain. They demonstrated that after adjustment for baseline EF, baseline longitudinal strain was associated with improvement in strain after TAVI. In terms of LV remodeling after TAVI, both EF groups had reductions in absolute and relative wall thickness and a trend toward a reduction in LV mass index, but only those with low EF at baseline had reductions in LV chamber volumes. Although this was a small study with the potential for survival bias, it adds important insight to our understanding of longitudinal strain and its change after LV unloading from TAVI, specifically in patients with low-flow, low-gradient AS.
Clinical Implications and Looking Forward
With any technological tool in medicine, there can be a tendency to focus on the tool and its measurement rather than the patient and the tool’s potential clinical utility. So with LV mechanics and the measurement of strain in patients with AS, it is important to consider how this tool can be used to improve clinical management and outcomes. Both the measurement of baseline indices as well as the change in LV mechanics, particularly longitudinal strain, have the potential to influence clinical management and treatment decisions.
Clinical Implications and Looking Forward
With any technological tool in medicine, there can be a tendency to focus on the tool and its measurement rather than the patient and the tool’s potential clinical utility. So with LV mechanics and the measurement of strain in patients with AS, it is important to consider how this tool can be used to improve clinical management and outcomes. Both the measurement of baseline indices as well as the change in LV mechanics, particularly longitudinal strain, have the potential to influence clinical management and treatment decisions.
Potential Clinical Implications of Baseline Strain Measurements
For lower risk, asymptomatic patients with severe AS, strain assessment may have implications for the timing of valve replacement, in that those with reduced strain may benefit from earlier surgery to avoid further cardiac injury and dysfunction and to maintain long-term cardiac performance after valve replacement. Longitudinal strain may also be helpful to confirm whether a patient has paradoxical low-flow, low-gradient severe AS (compared with moderate AS or a measurement error), as these patients generally have more advanced myocardial disease and adverse remodeling, which manifests in reduced strain. This categorization may have treatment implications. Strain assessment may also be helpful in patients with low-flow, low-gradient severe AS and reduced EF to prict who might recover LV function and benefit from valve replacement. This patient population can present particularly difficult management decisions, and strain may provide important prognostic information beyond EF and the assessment of flow reserve with low-dose dobutamine infusion.
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