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- Published online May 7, 2018.
- paradoxical low-flow low-gradient severe aortic stenosis
- paradoxical low-flow severe aortic stenosis
- small body
- stroke volume index
- transcatheter aortic valve replacement
In the 1970s, I was a young cardiologist in training and becoming a young cardiology faculty member. At that point in time, the noninvasive evaluation of aortic stenosis was done by stethoscope, apex cardiography, phonocardiography, carotid pulse tracing, and M-mode echocardiography. Invasively, it was determined by cardiac catheterization, for which gradients and valve areas were calculated. The advent of 2-dimensional echocardiography and then continuous-wave Doppler (I was fortunate enough to be in on the early use and clinical validation of both) expanded the noninvasive evaluation of the patient with suspected aortic stenosis. Doppler-derived peak and mean gradients, as well as aortic valve area, determined by the continuity equation, became increasingly important in telling whether a patient had significant aortic stenosis. It seemed at the time, with severe aortic stenosis, it was simple—patients either had it or did not. However, as we know with many things in life, it is not as simple as that. There have been and will continue to be instances in which echo-derived data do not appear to correlate with hemodynamic findings or even clinical assessment of patients with presumed or known aortic stenosis.
As we now recognize, it appears that aortic stenosis comes in different forms, from those with high gradients and normal left ventricular ejection fraction (LVEF) to those with paradoxical low-gradient, low-flow aortic stenosis with or without preserved LVEF. In 2007, Hachicha et al. (1) described the concept of paradoxical low-flow aortic stenosis with a preserved EF. This led to the recognition that this condition typically occurred in older adult women, especially those with small body surface areas, and in those with severe concentric LV hypertrophy, small LV cavities, and LV volumes, as well as those with impaired diastolic filling of the left ventricle and/or increased hemodynamic afterload or hemodynamic impedance. It now appears that the prevalence of this condition alone could be anywhere from 3% to 24% of those presenting with presumed aortic stenosis.
In this issue of iJACC, Kataoka et al. (2) highlight the importance of a low stroke volume index (<35 ml/m2) as a predictor of outcome in older adult Japanese patients with aortic stenosis who underwent transcatheter aortic valve replacement (TAVR). However, before we discuss the findings of these investigators, we should remind ourselves of known facts that are very important when evaluating patients with presumed aortic stenosis.
The gradient across the stenotic valve is determined by the volume of blood that flows across that valve obstruction; hence, the higher the flow across a relatively fixed valvular obstruction, the higher the gradient should be, and vice versa. We also know that the gradient across the aortic valve is determined not only by the stroke volume, but also by the duration of the systolic ejection time with each beat and the systolic pressure in the ascending aorta, namely, the hemodynamic afterload or impedance. In addition, we have learned that a normal LVEF does not mean that the cardiac output is normal. Finally, it is becoming widely recognized that while the severity of aortic stenosis is primarily judged by the aortic valve gradients and aortic valve area, the single most important determinant of both of these is the stroke volume or stroke volume index.
Kataoka et al. (2) looked at 723 consecutive older adult Japanese patients with a mean age of 85 years, two-thirds of whom were women with small body surface areas (mean body surface area of 1.4 m2) who underwent TAVR. The investigators looked at many factors associated within the outcomes and late mortality after TAVR in these patients, but they focused particularly on stroke volume index. There was an ongoing debate among the Japanese colleagues that paradoxical low-flow severe aortic stenosis was not associated with a poor prognosis. However, these investigators found that a low stroke volume index (<35 ml/m2) was associated with increased all-cause mortality and increased cardiovascular mortality in those patients who underwent TAVR versus patients with severe aortic stenosis who had normal flow and a normal LVEF. They also found that paradoxically low-flow, low-gradient aortic stenosis with preserved EF was also associated with increased all-cause mortality. The unifying factor appeared to be knowledge of what the stroke volume index was in any particular patient who was evaluated for aortic stenosis. The investigators believed that stroke volume index was extremely important as a prognostic and risk stratification factor for predicting outcomes in patients in Japan who were being considered for or who were undergoing a TAVR, regardless of body surface area.
Le Ven et al. (3) determined that low-flow, but not low LVEF or low-gradient, was an independent predictor of mortality in patients with severe aortic stenosis. These investigators also suggested that stroke volume index should be integrated into any assessment of the risk with interventions. Although the present study by Kataoka et al. (2) does not provide substantial new insights into our knowledge of the importance of stroke volume index as a valuable prognostic and diagnostic finding in patients who are undergoing TAVR, it does clarify this issue among the Japanese colleagues and Japanese patients. Hence, it appears that a low stroke volume index (<35 ml/m2) is clearly associated with an increased all-cause mortality and cardiovascular mortality in patients who undergo TAVR.
So where does this leave us in trying to evaluate patients with suspected significant aortic stenosis in 2017? There are a plethora of flow diagrams that can be used, but it seems that there might be some simple factors to keep in mind when encountering patients with suspected significant aortic stenosis.
1. Because it is stroke volume that is critical to determining the gradients and the valve area, the stroke volume should be diligently measured and indexed to body surface area.
2. We must continually recognize that the existence of significant hypertension, which produces a significant afterload or arterial impedance, can critically influence the gradients that are obtained, either by invasive or noninvasive means. Hence, blood pressure must be taken into account when evaluating the severity of aortic stenosis based upon gradient measurements.
3. Recently, Berthelot-Richer et al. (4) highlighted the importance of aortic valve area calculation, especially in patients who had a discrepancy between aortic valve area and mean gradients, in assessing the survival benefit of patients who are being considered for surgical AVR. Hence, although there are many pitfalls to the noninvasive calculation of aortic valve area, it remains an important measurement in evaluating patients with aortic stenosis.
4. Although not mentioned in this paper, the degree of valve calcification and calcium burden, as detected by multidetector computed tomography, is becoming increasingly important in determining the presence of severe aortic stenosis, especially in the setting of low-flow, low-gradient aortic stenosis. These values offer not only diagnostic but also prognostic information. Hence, in patients in whom there are equivocal or conflicting data about the severity of aortic stenosis, calcium scoring of the aortic valves, derived from multidetector computed tomography, is important to consider.
5. Although the current American Heart Association/American College of Cardiology 2014 Valve Guidelines (5) make a distinction about whether the patient is symptomatic, should we not really be worrying about whether the LV is symptomatic? Hence, some evaluation of LV structure and function, beyond simple LVEF, should be undertaken. So whether LV longitudinal global strain is determined by using echocardiographic evaluation or magnetic resonance imaging testing to determine the extent of myocardial fibrosis, the health of the LV is important, because it will determine outcomes from interventions.
6. Finally, exercise testing, carefully performed by knowledgeable physicians, can be of great value in determining whether the “asymptomatic patient” with aortic stenosis is truly asymptomatic.
The paper by Kataoka et al. (2) clearly highlights the importance of LV stroke volume and stroke volume index in the evaluation of patients with presumed or known aortic stenosis. However, understanding the importance of considering the previously mentioned factors will make us better able to evaluate not only the severity of the aortic stenosis, but determine the appropriate interventions for each patient at the appropriate time.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Martin is Emeritus Professor of Medicine at Emory University School of Medicine; a member of the Speakers Bureau of Abbott Structural Heart, Edwards Lifesciences Heart Valve Therapy, and Medtronic Heart Valve Therapies; and is a stockholder in Bay Labs, Inc.
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