Author + information
- Received July 9, 2017
- Revision received November 2, 2017
- Accepted November 20, 2017
- Published online January 29, 2018.
- Mohamed-Salah Annabi, MDa,
- Eden Touboul, PharmDa,
- Abdellaziz Dahou, MD, PhDa,
- Ian G. Burwash, MDb,
- Jutta Bergler-Klein, MDc,
- Maurice Enriquez-Sarano, MDd,
- Stefan Orwat, MDe,
- Helmut Baumgartner, MDe,
- Julia Mascherbauer, MDc,
- Gerald Mundigler, MDc,
- João L. Cavalcante, MDf,
- Éric Larose, MD, MSca,
- Philippe Pibarot, DVM, PhDa and
- Marie-Annick Clavel, DVM, PhDa,d,∗ ()
- aInstitut Universitaire de Cardiologie et de Pneumologie, Université Laval, Québec, Canada
- bUniversity of Ottawa Heart Institute, Ottawa, Ontario, Canada
- cDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
- dDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- eDivision of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
- fDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh/UPMC, Pittsburgh, Pennsylvania
- ↵∗Address for correspondence:
Dr. Marie-Annick Clavel, Institut Universitaire de Cardiologie et de Pneumologie, Université Laval, 2725 Chemin Ste-Foy #A-2047, Quebec G1V 4G5, Canada.
Background In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated.
Objectives The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS).
Methods One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVAProj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis.
Results Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm2, and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1 cm2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1 cm2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003).
Conclusions In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)
Although patients with depressed left ventricular ejection fraction (LVEF ≤50%) low-flow, low-gradient (LF-LG) aortic stenosis (AS) represent only 5% to 10% of the AS population, they constitute a highly challenging subset with regard to the assessment of AS severity and therapeutic decision making (1). In the presence of a LF state, the mean transvalvular pressure gradient (MG) can underestimate the stenosis severity due to its flow dependence, whereas the aortic valve area (AVA) may overestimate the stenosis severity due to incomplete opening of the valve orifice because of reduced opening forces (pseudo-severe AS [PSAS]). Hence, at rest, the patient often presents with discordant grading of AS severity, in which AVA is <1.0 cm2, which suggests severe AS, but the MG is <40 mm Hg, which suggests nonsevere AS. In the current American College of Cardiology/American Heart Association (ACC/AHA) valve guidelines (1), this entity is labeled “classical LF-LG AS” and is defined as an AVA ≤1.0 cm2, a MG <40 mm Hg, and a LVEF <50%. Dobutamine stress echocardiography (DSE) has been shown to be useful in overcoming the discordant grading observed in these patients because it can identify the presence of true-severe AS (TSAS) (2). In the ACC/AHA valve guidelines (1), these patients are considered to have TSAS, and thus, they have an indication for aortic valve replacement (AVR) (Class IIa recommendation) if the MG is ≥40 mm Hg with an AVA ≤1.0 cm2 during DSE (1). However, these DSE criteria to distinguish AS severity in low LVEF LF-LG AS have not been well validated.
Our objective was to evaluate the usefulness of the MG and AVA of the DSE criteria proposed in the guidelines to predict stenosis severity and the outcome of patients with low LVEF LF-LG AS.
A total of 186 patients were prospectively recruited in the TOPAS (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis) study. The design and methods of this prospective multicenter observational study have been previously described (3–5). Patients were included in the TOPAS study if they had a MG <40 mm Hg, an indexed AVA ≤0.6 cm2/m2, and a LVEF ≤40% on a resting echocardiogram. Patients were excluded if they had more than mild aortic regurgitation, moderate mitral regurgitation, or mild mitral stenosis, as assessed by the multiparametric integrative approach recommended in the current guidelines for native valve regurgitation and stenosis (6–8). The study was approved by the institutional review board committee of the participating centers, and the patients provided informed consent. At study entry, all patients underwent echocardiography at rest and with dobutamine stress. A subset of patients (those recruited after 2009) underwent multidetector computed tomography (MDCT) for the quantitation of aortic valve calcification. Clinical data were collected and included age, sex, body surface area, Duke activity status index, hypertension (patients receiving antihypertensive medications or having known, but untreated, hypertension [blood pressure ≥140/90 mm Hg]), diabetes, renal failure, hyperlipidemia, coronary artery disease (history of myocardial infarction or ≥50% coronary artery stenosis on coronary angiography), congestive heart failure, acute pulmonary edema, and chronic obstructive pulmonary disease. The treatment (AVR or medical management) was left to the discretion of the treating physician who was blinded to the projected AVA and aortic valve calcium scoring data but not to the standard resting and DSE parameters of AS severity (resting and stress AVA and MG). Patients were followed, in accordance with protocol, annually for 5 years.
Resting Doppler echocardiograms and DSE were performed using a commercially available ultrasound system. The dobutamine infusion protocol consisted of 8-min stages with increments of 2.5 to 5 μg/kg/min up to a maximum dosage of 20 μg/kg/min (3). LV dimensions were measured at rest according to American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (8). LV outflow tract diameter was measured at rest and considered constant during DSE. The following measurements were performed at rest and at each DSE stage: stroke volume was measured in the LV outflow tract; transvalvular flow rate (Q) was obtained by dividing stroke volume by the LV ejection time measured on the continuous-wave Doppler spectral envelope of aortic flow; AVA was calculated by the continuity equation; MG was obtained by the Bernoulli formula; and LVEF was measured using the biplane Simpson method. For all these parameters, we averaged the measures of 3 cycles in normal sinus rhythm and 5 cycles in the presence of irregular rhythm. The projected AVA (AVAProj) at a normal transvalvular flow rate (250 ml/min) was calculated using the equation (9):where AVARest and AVAPeak are the AVA at rest and at peak stress, and QRest and QPeak were Q at rest and at peak stress. To be consistent with the guideline criteria, peak stress values were obtained at the time when MG was maximal during DSE, which did not necessarily correspond to the last stage with a maximum dobutamine dose. Likewise, AVAPeak and QPeak were the values of AVA and QPeak concomitant to MGpeak.
Assessment of AS severity
AS severity was assessed in 87 patients by 1 of 2 methods: 1) macroscopic evaluation of the valve by the cardiac surgeon at the time of AVR; or 2) quantitation of aortic valve calcification by MDCT. For the macroscopic evaluation, the surgeon visually inspected the valve at the time of AVR and classified the valve stenosis severity as nonsignificant, mild, moderate, or severe using a standardized method described in previous publications (3,9). Briefly, each valve leaflet was evaluated for stiffness (scored from 0 to 3, 0 being entirely flexible) and degree of calcification (scored from 0 to 3, 0 being noncalcified). Scores for stiffness and calcification were summed and divided by the number of leaflets, giving an average per leaflet score. Among the 62 patients assessed visually by the surgeon, 36 valves were described as TSAS (AS graded as severe), whereas 26 valves were considered to be PSAS (AS graded as moderate or less) (Figure 1).
In 33 patients, AS severity was corroborated by the quantitation of aortic valve calcium load by MDCT (Figure 1). TSAS was considered present when the aortic valve calcium load was >1,200 Agatston units (AU) for women and >2,000 AU for men, as previously validated (10,11). Of the 33 patients in whom this method was used, 19 (58%) had TSAS according to MDCT assessment. In the 8 patients with both surgeon assessment and aortic valve calcium scoring, there was an 88% (7 or 8 patients) agreement in the classification of stenosis severity (Figure 1).
Figure 1 describes the subgroups that were used for each analysis. Results are expressed as mean ± SD, unless otherwise specified. Correlations among the assessment of AS severity and AVAPeak, MGPeak, and AVAProj were determined by simple logistic regression analysis. Receiver-operating characteristic curves were used to determine the area under the curve, sensitivity, specificity, positive and negative predictive values, and percentage of correct classification for these variables at several cutoff values. Based on previous studies that reported that estimation of AVAProj might not be reliable when the percent flow rate increase was <15% (3,9), we excluded such patients from the receiver-operating characteristic analysis in the present study.
Accuracy of mortality prediction was determined for the cutpoints proposed in the ACC/AHA guidelines for AVAPeak, MGPeak, and for AVAProj ≤1 cm2 using Kaplan-Meier survival curves and Cox proportional hazards models, and the corresponding curves were adjusted for age, sex, functional capacity (as documented by the Duke activity status index), kidney failure, and LVEFPeak (LVEF at peak dobutamine stress) in patients who received medical management.
The net reclassification index using the category free net reclassification index and integrated discrimination agreement program codes downloaded online was used to determine the incremental predictive value of AVAProj ≤1 cm2 beyond guideline parameters (AVAPeak and MGPeak) for predicting 1-year mortality under medical management. A p value <0.05 was considered statistically significant. Statistical analyses were performed with JMP version 13.0.0 (SAS Institute Inc., Cary, North Carolina, 1989-2007) and STATA version 11 (StataCorp, College Station, Texas) software.
The study population was a mean age of 73 ± 10 years and had a larger proportion of men (78%) (Table 1). There was a high prevalence of comorbidities, including diabetes (41%), hypertension (68%), coronary artery disease (76%), and previous myocardial infarction (55%) (Table 1). LVEF was 28 ± 8%, QRest was 190 ± 49 ml/s, MGRest was 23 ± 8 mm Hg, and AVARest was 0.88 ± 0.22 cm2. With DSE, the average transvalvular flow rate and hemodynamic parameters of AS severity increased significantly (Table 1). However, 26% of patients had a QPeak <220 ml/s and thus did not reach the normal flow rate despite dobutamine stress. In contrast, 32% achieved a supranormal flow rate (>300 ml/s) during DSE, whereas only 42% had a peak flow rate in the normal range (230 to 300 ml/s). Among the 186 patients included in this study, 98 (53%) underwent AVR, 71 (38%) by standard open-heart surgery, and 27 (15%) by transcatheter access.
Assessment of AS severity
AVAProj and AVAProj indexed to body surface were significantly smaller in patients with TSAS versus PSAS (0.88 ± 0.16 cm2 vs. 0.99 ± 0.23 cm2; p = 0.01 and 0.45 ± 0.07 cm2/m2 vs. 0.54 ± 0.14 cm2/m2; p = 0.0005, respectively), whereas AVAPeak and MGPeak were not different (0.93 ± 0.24 cm2 vs. 1.02 ± 0.23 cm2; p = 0.07 and 38.2 ± 10.3 mm Hg vs. 34.5 ± 11.8 mm Hg; p = 0.12, respectively). MGPeak ≥40 mm Hg had a low sensitivity of 35%, a positive predictive value of 57%, and a lower percentage of correct AS severity classification of 48% for the identification of TSAS (Table 2). Lowering the MGPeak cutoff value to 35 mm Hg for identifying TSAS improved the sensitivity (69%), positive predictive value (61%), and percentage of correct classification (63%). A MGPeak cutoff value of 30 mm Hg resulted in a percentage correct classification of 60%. AVAPeak ≤1 cm2 had a sensitivity of 63%, a positive predictive value of 64%, and a percentage correct classification of 60%. The combination of MGPeak ≥40 mm Hg and AVAPeak ≤1 cm2 had a lower percentage of correct classification (47%) compared with AVAPeak ≤1 cm2 alone. AVAProj and indexed AVAProj had the best area under the curve, sensitivity, and positive predictive value compared with the other DSE parameters (Table 2). Indexed AVAProj ≤0.6 cm2/m2 had the best performance to identify TSAS with an area under the curve of 0.70, sensitivity of 94%, positive predictive value of 66%, and a percentage correct classification of 68% (Table 2). An AVAProj ≤1 cm2 provided similar results with a percentage correct classification of 70%.
Prediction of patient outcome
In univariable analysis, MGPeak, AVAPeak, AVAProj, and indexed AVAProj as continuous variables were predictors of mortality (all p ≤ 0.02). As dichotomous variables only AVAProj ≤1 cm2 (p < 0.0001) and indexed AVAProj ≤0.55 cm2/m2, (p = 0.004) were predictors of mortality, whereas MGPeak ≥40 mm Hg (p = 0.69) and AVAPeak ≤1 cm2 (p = 0.06) were not (Figure 2 and Table 3). The combination of AVAPeak ≤1 cm2 and MGPeak ≥40 mm Hg as recommended in the guidelines to identify TSAS was not associated with all-cause mortality (p = 0.21).
After adjustment for age, sex, functional capacity, kidney disease, and LVEFPeak, AVAProj and indexed AVAProj (as continuous or dichotomous variables), and MGPeak and AVAPeak (as continuous variables only) were independent predictors of mortality during medical management (all p ≤ 0.02) (Figure 2). There was a trend toward significance of AVAPeak ≤1 cm2 to predict mortality during medical management (p = 0.06) (Figure 2 and Table 3).
Models built with AVAProj or indexed AVAProj were more accurate in predicting mortality than those built with AVAPeak or MGPeak (all p ≤ 0.05). AVAProj ≤1 cm2 had a net reclassification index of predicting death under medical management at 1 year of 0.96 compared with AVAPeak ≤1 cm2 (p < 0.0001), 0.60 compared with MGPeak ≥40 mm Hg (p = 0.01), and 0.88 compared with the composite of MGPeak ≥40 mm Hg and AVAPeak ≤1 cm2 (p = 0.0003).
Adding atrial fibrillation in the models did not change the results of the Cox analyses. Flow reserve defined by a percent increase in stroke volume ≥20% during DSE was not associated with mortality (p = 0.80 and p = 0.66 in univariable and multivariable analyses, respectively).
The main findings of this study are that in patients with low LVEF LF-LG AS: 1) a DSE criteria of MGPeak ≥40 mm Hg has a low sensitivity for identifying TSAS and does not predict mortality in medically managed patients; lowering the cutoff value of MGPeak to 35 mm Hg can improve the sensitivity; 2) a DSE criteria of AVAPeak ≤1.0 cm2 is superior to MGPeak criteria to identify TSAS and predict mortality; 3) a combination of MGPeak ≥40 mm Hg and AVAPeak ≤1.0 cm2 as proposed in the ACC/AHA valve guidelines has a low sensitivity for identifying TSAS and does not predict mortality in medically managed patients; and 4) AVAProj provides the best accuracy to predict TSAS and clinical outcomes with an AVAProj ≤1.0 cm2 (or indexed AVAProj ≤0.55 cm2/m2) providing the optimal cutoff value (Central Illustration).
Flow dependence of parameters of AS severity
Echocardiography or catheterization measures of AS severity such as MG and AVA are inherently flow dependent (3,12,13). Because the transvalvular flow response to dobutamine varies largely from one patient to another (12,13), peak DSE values of AVA and MG do not solely represent the severity of the valve stenosis, but may be influenced by the magnitude of the change in flow during dobutamine stress. In the present study, approximately one-half of patients did not have normal flow rate during dobutamine stress, which could potentially lead to persistence of the discordance in AS severity grade based on MG and AVA. In addition, 25% of patients achieved supranormal flow rates during dobutamine stress, which could lead to “reverse” discordant grading by AVA and MG (AVA >1 cm2 and MG ≥40 mm Hg). The projected AVA at a normal flow rate has the advantage of being standardized for the transvalvular flow rate. This parameter provides an estimation of the AVA at a fixed normal flow rate that is identical for all patients (i.e., 250 ml/s) (3,9). This standardization for flow rate might explain why the AVAProj outperforms other DSE parameters for the prediction of stenosis severity and outcomes in low LVEF LF-LG AS.
Criteria to differentiate TSAS and PSAS in low LVEF LF-LG AS
The DSE criteria of MGPeak ≥40 mm Hg lacks sensitivity to differentiate TSAS and PSAS. Using a lower cutoff value of MGPeak ≥35 mm Hg markedly improved the sensitivity from 35% to 69% while also improving the percentage of correct classification from 48% to 63%. The use of a cutoff of 30 mm Hg did not further improve the diagnostic performance of MGPeak. The low sensitivity of MGPeak criteria might be related to the fact that almost one-half of patients with low LVEF LF-LG AS did not achieve a normal flow rate with DSE, thus potentially precluding MG to reach 40 mm Hg despite the presence of TSAS. Using a DSE criteria of AVAPeak ≤1.0 cm2 had better sensitivity and percentage of correct classification compared with MGPeak. Use of a cutoff value of <1.2 cm2 as suggested in some studies (4,9,14) further improved the sensitivity (63% to 84%). However, the main limitation of AVAPeak criteria was the relatively low specificity. Because achieving a normal flow rate of 250 ml/s with stress fails in a large proportion of patients, AVAPeak might still be pseudo-severe due to a persistent LF state. Using the combination of MGPeak ≥ 40 mm Hg and AVAPeak ≤ 1.0 cm2 as proposed in the ACC/AHA guidelines improved the specificity, but had a low sensitivity at only 22% and a percentage of correct classification of only 47% in our study cohort. The projected AVA at a normal flow overcomes the flow dependency of MGPeak and AVAPeak, and thereby improves the accuracy of DSE for the identification of TSAS and PSAS. However, a minimum 15% increase in mean transvalvular flow rate is required to obtain a reliable estimate of AVAProj during DSE (9). In patients with low LVEF LF-LG AS and no or minimal increase (<15%) in flow rate (11% of the patients in the present series), it is likely preferable to use aortic valve calcium scoring by computed tomography to corroborate stenosis severity (10).
DSE indexes of AS severity as predictors of mortality
There was no association between DSE MGPeak ≥40 mm Hg and mortality in our low LVEF LF-LG AS patients who received medical management. This intriguing finding might be due to the fact that the increase in MG during DSE was not only related to the stenosis severity, but also influenced by LV contractile reserve (4,9,15,16). The presence of TSAS and lack of contractile reserve are known risk factors for mortality in low LVEF LF-LG AS (15,16), but have opposite effects on MGPeak. A more severe stenosis is associated with a larger increase in MG during DSE, whereas a lack of contractile reserve, and thus flow reserve, due to advanced myocardial impairment, is associated with a smaller increase in MG. Hence, a lower MGPeak does not necessarily indicate the presence of nonsevere AS, but may be observed in a patient with TSAS in whom the increase in MGPeak has been blunted by poor flow reserve. Such patients would be at high risk of mortality under conservative management (15,16). Up to two-thirds of patients in our cohort with a MGPeak <40 mm Hg and AVAPeak ≤1.0 cm2 had TSAS. Furthermore, there were several patients (n = 8) with a MGPeak <40 mm Hg and AVAPeak between 1.0 and 1.2 cm2 who were found to have TSAS based on surgical inspection or aortic valve calcium load. Hence, the presence of a MGPeak <40 mm Hg and/or an AVAPeak >1.0 cm2 on DSE does not exclude the presence of TSAS and a potential benefit from AVR.
As opposed to MGPeak, the presence of TSAS and the lack of flow reserve both yield a smaller AVAPeak (i.e., the effect of these 2 factors affect AVAPeak in the same direction, as opposed to in opposite directions on MGPeak). Hence, a small AVAPeak may be a marker of a more severe AS, more advanced myocardial impairment, or both. This might explain why in univariable analyses, AVAPeak was strongly associated with an increased risk of mortality in medically treated patients, whereas MGPeak was not. After adjusting for other DSE markers of LV myocardial impairment (such as peak stress LVEF), the association between AVAPeak and outcome was no longer significant.
As opposed to MGPeak and AVAPeak, AVAProj is standardized for flow and is a more precise marker of the actual AS severity. Furthermore, this parameter is independent of LV function and transvalvular flow. This might explain why a small AVAProj, which reflected the presence of TSAS, was independently associated with an increased risk of mortality in patients treated conservatively, even after adjustment for DSE parameters of LV function.
Residual confounding factors could not be excluded in this observational study. The treatment was left to the discretion of the treating physician who was aware of the AVA rest/peak and MPG rest/peak, stroke volume rest/peak (i.e., data included in the guidelines), but not of the AVAProj or the aortic valve calcification score. Despite being a limitation, this aspect of the protocol further reinforced the robustness of the results and conclusions of the study. Patients with a MGPeak ≥40 mm Hg were underrepresented in the medical management group because they were more likely to undergo aortic valve replacement. However, even as continuous variable, MGPeak appeared to be a weaker predictor of mortality than AVAProj.
We primarily used the assessment of the valve by the cardiac surgeon at the time of AVR as the reference standard. Although this process had been standardized among the different sites participating to the TOPAS study, the assessment performed by the surgeon was only semiquantitative and was predominantly based on the anatomic severity rather than the hemodynamic severity. In a subset of patients, we used the aortic valve calcium score measured by MDCT to corroborate AS severity. Aortic valve calcification is a marker of “anatomic” severity and not a direct marker of hemodynamic severity. Nonetheless, several studies demonstrated that MDCT aortic valve calcium score was strongly associated with AS hemodynamic severity, progression rate, and clinical outcomes (10,11,17). However, aortic valve calcium score thresholds were never validated in these low LVEF LF-LG AS patients.
The use of MG ≥40 mm Hg with or without an AVA ≤1 cm2 during DSE leads to misclassification of AS severity in approximately one-half of patients with low LVEF LF-LG AS. The most important limitation of these DSE criteria is the low sensitivity due to persistence of a LF state during dobutamine stress and persistent discordant grading of AS severity using MG and AVA. Application of a lower cutoff value for peak stress MG ≥35 mm Hg improves the sensitivity of DSE for the identification of TSAS. Use of the projected AVA at a normal flow rate of 250 ml/s provides the best performance for correctly classifying AS severity and the best prediction of clinical outcome in patients with low LVEF LF-LG AS undergoing medical management. This parameter should be considered to guide patient management, especially when discordant AS grading persists despite DSE. Because of the major implications of accurate assessment of AS severity in these low LVEF LF-LG AS patients, other methods such as aortic valve calcium scoring by MDCT should be considered to corroborate AS severity in all cases. Further studies will be needed to validate aortic valve calcium thresholds in this population and to assess the complementarity of DSE and aortic valve calcium scoring.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: In patients with LF-LG AS and reduced LVEF who underwent DSE, calculation of AVAproj at a normal transvalvular flow rate (250 ml/min) more accurately identified patients with truly severe AS than use of the combination of MG ≥40 mm Hg and AVA ≤1.0 cm2.
TRANSLATIONAL OUTLOOK: Additional studies are needed to evaluate the complementary diagnostic value of aortic valve calcification assessed by MDCT imaging and calculation of the AVAproj by DSE to improve selection of patients with LF-LG AS for valve replacement.
This work was supported by a grant (# MOP-57445 for TOPAS-II and # MOP-126072 and FDN-143225 for TOPAS-III) from the Canadian Institutes of Health Research, Ottawa, Canada. Dr. Dahou was supported by a fellowship grant from “L’Agence de la santé et des services sociaux de la Capitale nationale-ADLSSS”, Québec, Québec, Canada. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research; and has received institutional research support from Edwards Lifesciences and Medtronic. Dr. Clavel holds a junior scholarship from Fonds de Recherche du Québec-Santé (FRQS).
Dr. Dahou has received a research grant from Grant Edwards LLC. Dr. Baumgartner has received travel support from Edwards Lifesciences, Medtronic, Abbott, and Actelion; and has received speaker fees from Edwards Lifesciences. Dr. Cavalcante has received a research grant from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Annabi and Touboul contributed equally to this work and are joint first authors on this paper.
- Acronyms and Abbreviations
- American College of Cardiology/American Heart Association
- aortic stenosis
- aortic valve area
- projected AVA
- aortic valve replacement
- dobutamine stress echocardiography
- low-flow, low-gradient
- left ventricle/left ventricular
- LV ejection fraction
- multidetector computed tomography
- mean gradient
- pseudo-severe AS
- transvalvular flow rate
- true-severe AS
- Received July 9, 2017.
- Revision received November 2, 2017.
- Accepted November 20, 2017.
- 2018 American College of Cardiology Foundation
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