Searching for the Best Echo Parameter to Predict Aortic Stenosis Outcomes
By Michael H. Crawford, MD, Editor
SYNOPSIS: In a study of two large echocardiographic databases, the authors observed maximum aortic velocity exhibits a strong linear relationship, with the risk of mortality starting at velocities of 100 cm/s, whereas calculated aortic valve area was not related to mortality until the valve area was <1.5 cm2.
SOURCE: Alcón B, Martínez-Legazpi P, Stewart S, et al. Transvalvular jet velocity, aortic valve area, mortality, and cardiovascular outcomes. Eur Heart J Cardiovasc Imaging 2022; Feb 6:jeac003. doi: 10.1093/ehjci/jeac003. [Online ahead of print].
The risk of adverse cardiovascular outcomes increases progressively as the severity of aortic stenosis (AS) increases, but little is known about which echocardiographic parameters best predict this risk. Investigators from Spain and Australia measured maximum aortic valve velocity (Vmax) and aortic valve area (AVA) in all adult echocardiograms performed at a hospital in Madrid from 2015-2016, including patients with and without AS.
Studies with prosthetic aortic valves as well as supra- or subvalvular stenosis were excluded. The primary endpoints were all-cause mortality, cardiovascular mortality, any cardiovascular event, heart failure events, and the number of heart failure events every two years. The secondary endpoint was non-cardiovascular events. These endpoints were assessed by chart review over a five-year follow-up period — except for cardiovascular mortality, which was assessed using the Australian New Zealand Clinical Trials Registry (NEDA) echocardiographic database (112,690 patients). Complete data over a median 4.5-year follow-up were available for 5,994 patients (mean age 70 years, 56% men with significant comorbidities [mean Charlson Comorbidity Index score = 3.6]).
During the follow-up period, 833 patients were admitted for a cardiovascular event, 101 underwent aortic valve replacement, and 2,119 died. There was a linear relationship between Vmax and all-cause mortality, which became evident at 150 cm/s to 200 cm/s. Also, Vmax was related to the risk of cardiovascular events, mainly because of an increased risk of heart failure events, which was evident beginning in the 150 cm/s to 200 cm/s range (HR, 1.26; 95% CI, 1.04-1.53) and doubled in the 200 cm/s to 300 cm/s range. There was no association with Vmax and other cardiovascular or non-cardiovascular events. AVA was associated with all the primary endpoints, but the risk relationship was non-linear, remaining flat until AVA was less than 2.0 cm2. For example, the 42% mortality risk at an AVA of 1.0 cm² was reached at a Vmax value of 292 cm/s. This mismatch between Vmax and AVA was more marked in those with low flow. These results were confirmed in the NEDA population. In addition, when the results were adjusted for relevant comorbidities, such as ejection fraction and coronary artery disease, the results remained significant. The authors concluded the risk of all-cause and cardiovascular mortality, as well as heart failure events, are robustly associated with AS and are apparent at the early stages of the disease. However, the grading of AS severity by Vmax and AVA were mismatched in relation to outcomes.
COMMENTARY
The accurate grading of the severity of AS is a challenge for the echocardiographic laboratory. Most labs do not attempt to quantify the degree of AS unless the Vmax is > 200 cm/s and the AV is sclerotic or calcified. Thus, prior observational studies of outcomes in AS may have been biased toward more severe cases.
The Alcón et al study is unique in that all echocardiograms were included, with exclusions only for other types of left ventricular outflow obstruction. Their data suggest the cutoffs for various severities of AS by Vmax and AVA may need to be revised. In particular, the authors showed risk of adverse outcomes in moderate AS (Vmax rate = 300 cm/s to 400 cm/s) were worse than severe AS by AVA (< 1.0 cm2). AVA normalizes for flow; in this study, the mismatch between AVA and Vmax was greater in low-flow patients. Other factors not identified in this study may be at play here. For example, in the Vmax 150 cm/s to 200 cm/s group, one-third did not exhibit sclerosis or calcium of the aortic valve, and the adverse risk persisted when corrected for stroke volume, anemia, and other factors. The higher risk was not seen in AVAs in the 2 cm2 to 2.5 cm2 group, which should correlate to the 150 cm/s to 200 cm/s Vmax group.
Interestingly, the major adverse outcome observed was the development of heart failure, not vascular events. Perhaps this is because the pressure load on the LV with higher degrees of AS is not seen in the vasculature as it is in hypertension. With less severe AS, the faster velocity of flow may lead to vascular damage that explains the higher mortality rate.
Since this was an observational study, there may be unmeasured confounders for which the investigators could not adjust. Also, these clinical data are insufficient to determine the mechanism of the findings. In addition, the authors mainly studied events that required hospitalization, so the study population may be skewed toward sicker patients. Finally, the authors did not consider subsequent echoes. Accordingly, some patients may have progressed to severe AS during the follow-up period. However, the authors noted this is unlikely to be a major factor. Their data show it takes an average of eight years to progress from a Vmax of 100 cm/s to 200 cm/s to one of 400 cm/s, and their follow-up period was four to five years, on average.
With the advent of transcatheter aortic valve replacement, waiting for clearly severe symptomatic AS to develop may not make sense anymore. Perhaps the guidelines should be revised to recommend AV replacement at an earlier stage. The data collected by Alcón et al support such a concept, but cannot be used to recommend replacement for patients with Vmax faster than 200 cm/s. Any step in this direction would require other researchers to conduct a randomized clinical trial.
In a study of two large echocardiographic databases, the authors observed maximum aortic velocity exhibits a strong linear relationship, with the risk of mortality starting at velocities of 100 cm/s, whereas calculated aortic valve area was not related to mortality until the valve area was <1.5 cm2.
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