Author + information
- Received May 31, 2011
- Revision received August 3, 2011
- Accepted August 9, 2011
- Published online January 17, 2012.
- Patrizio Lancellotti, MD, PhD⁎,⁎ (, )
- Julien Magne, PhD⁎,
- Erwan Donal, MD, PhD†,
- Laurent Davin, MD⁎,
- Kim O'Connor, MD⁎,‡,
- Monica Rosca, MD⁎,
- Catherine Szymanski, MD⁎,
- Bernard Cosyns, MD, PhD§ and
- Luc A. Piérard, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Patrizio Lancellotti, Department of Cardiology, University Hospital Sart Tilman, B-4000 Liege, Belgium
Objectives This study examined the clinical course of patients with asymptomatic severe aortic stenosis (AS) according to the new proposed aortic valve stenosis grading classification.
Background The management of patients with asymptomatic severe AS remains controversial. Moreover, under the same denomination of severe AS, several entities might be identified according to transvalvular flow rates and pressure gradients, resulting in 4 flow-gradient patterns.
Methods Transthoracic echocardiography and measurement of B-type natriuretic peptide level from venous blood sample were performed in 150 consecutive patients with asymptomatic severe AS and normal exercise test. Patients were classified in 4 groups, depending on left ventricular flow state (normal flow [NF] vs. low flow [LF]: 35 ml/m2) and pressure gradient levels (low gradient [LG] vs. high gradient [HG]: 40 mm Hg).
Results Patients with NF/LG had significantly lower B-type natriuretic peptide than those with LF/HG and LF/LG. The mean follow-up was 27 ± 12 months. At 2 years, cardiac event-free survival was 83 ± 6%, 44 ± 6%, 30 ± 12%, and 27 ± 13% in NF/LG, NF/HG, LF/HG, and LF/LG groups, respectively (p < 0.0001). On multivariable analysis, LF/LG (hazard ratio [HR]: 5.26, 95% confidence interval [CI]: 2.04 to 14.3, p = 0.045) and LF/HG (HR: 2.38, 95% CI: 1.02 to 5.55, p = 0.001) were identified as strong independent determinants of poor prognosis as compared with NF/HG. By limiting the multivariable analysis to patients with LF, LF/LG was an independent predictor of markedly reduced cardiac event-free survival when compared with LF/HG (HR: 5.4, 95% CI: 1.03 to 28.6, p = 0.046).
Conclusions The use of the new proposed AS grading classification integrating valve area and flow-gradient patterns allows a better characterization of the clinical outcome of patients with asymptomatic severe AS.
Valvular aortic stenosis (AS) is a growing health problem with sizeable economic impact. Treatment decisions in AS are mainly based upon the symptomatic status of the patient and the severity of AS. Aortic valve replacement (AVR) is currently indicated in patients with severe AS who develop symptoms. The management of asymptomatic patients with severe AS remains a source of debate. In these patients, recent studies have brought out that early elective surgery might be more beneficial than medical therapy (1)—namely, the “wait for symptoms strategy.” This difference might be related to underestimation of symptoms and/or stenosis severity in some patients. According to current American College of Cardiology/American Heart Association guidelines (2), cutoff values for Doppler-echocardiographic measurements of severe AS are defined as follows: aortic valve area (AVA) <1.0 cm2, mean gradient >40 mm Hg, and peak velocity >4.0 m/s. However, recent studies have emphasized that the criteria for grading AS severity are inherently inconsistent, even in patients with normal left ventricular (LV) systolic function (3). Under the same denomination of severe AS, several entities might be identified that differ in terms of transvalvular flow rates and pressure gradients develop. Hence, from a clinical standpoint, severe AS (AVA <1 cm2) can be subdivided into 4 flow-gradient patterns. Of note, this discordance between gradient and AVA often reflects the presence of a paradoxical low-flow (LF) state in which the stroke volume is unexpectedly reduced, despite preserved left ventricular ejection fraction (LVEF) (4). Such a pattern has been reported in up to 35% of patients with severe AS and seems to be consistent with a more advanced stage of the disease (increased global LV afterload, significant LV concentric remodeling, and intrinsic myocardial dysfunction) (4). Misinterpreting this clinical condition might lead to an inappropriate timing of follow-up with an unnecessary delay of AVR. In asymptomatic patients, risk stratification has been mostly evaluated in patients with a normal flow (NF)/high gradient (HG) pattern (5). In this group, the severity of stenosis, the degree of aortic valve calcification, the rate of progression of stenosis, the level of B-type natriuretic peptide (BNP), and an abnormal response to exercise have been shown to be associated with a poorer prognosis (6–9). By contrast, in the other AS categories, the outcome has never been specifically examined. Therefore, we prospectively studied the clinical course of a large cohort of consecutive patients with asymptomatic severe AS according to the new proposed AS grading classification.
We prospectively included consecutive patients with asymptomatic severe AS, defined as an AVA <1 cm2, referred to our outpatient clinic for valvular heart disease for an exercise test and a BNP measurement. Only patients with normal exercise test (no symptoms, normal blood pressure evolution, and no ventricular arrhythmias during the test) were considered for the final analysis of the study. The other exclusion criteria were: 1) LVEF <55%; 2) more than mild concomitant valvular heart disease; 3) atrial fibrillation; 4) pulmonary disease; and 5) inability to perform exercise test. The final studied population consisted of 150 patients (age 69.7 ± 8 years, 64% men). The collection of baseline demographic and clinical data was standardized and performed at the time of echocardiography.
A comprehensive transthoracic echocardiography was performed with the VIVID 7 ultrasound system (General Electric Healthcare, Little Chalfont, United Kingdom) in all patients. All Doppler-echocardiographic recordings were stored in digital format on a dedicated workstation for offline subsequent analysis. All echocardiographic measurement were performed as previously described by our group (6,8). Of note, LV stroke volume was calculated with both the Doppler (LV outflow tract area × LV outflow tract velocity–time integral measured by pulsed-wave Doppler) and the volumetric (bi-apical Simpson's method) methods. Moreover, multiple transducer positions were used to record peak aortic jet velocities. The highest transaortic velocity was used for tracing of the time-velocity integral and to calculate pressure gradients. For each measurement, at least 2 cardiac cycles were averaged.
BNP measurement and risk score
Venous blood samples for BNP measurement were drawn before echocardiography, after 10 min of supine rest. Chilled ethylenediaminetetraacetic acid tubes were centrifuged immediately at 4,000 rpm (4°C) for 15 min. Separated plasma samples were processed by immunofluorescence assay (Biosite, Beckman Coulter, San Diego, California). The inter- and intra-assay variation was 5% and 4%, respectively. The assay detection limit was 1 pg/ml. A predictive risk score—including BNP, sex, and aortic valve peak velocity—was calculated for each patient according to the recent work of Monin et al. (9). This score integrates the complex interplay between the aortic valve and the LV. It was validated in a multicenter study including patients with asymptomatic moderate-to-severe AS and was identified as useful for risk stratification of such patients.
Follow-up information was obtained every 6 to 12 months from standardized interviews with the patients, their physicians, or (if necessary) next of kin, according to guidelines (2,10). The primary outcome variable was the time to occurrence of the first composite endpoint, defined as cardiovascular death or need for AVR motivated by the development of symptoms or LV systolic dysfunction (LVEF <50%). The clinical management of the patients was determined independently by their personal physicians.
New proposed AS grading classification
Patient outcome was studied according to the new proposed AS grading classification (4). Patients were classified in 4 groups depending on LV flow state (NF vs. LF) and pressure gradient level (low gradient [LG] vs. HG). As previously described, LF was defined as an indexed LV stroke volume <35 ml/m2 (4), and LG was defined as a mean transaortic pressure gradient <40 mm Hg (11). This classification results in the following 4 flow-gradient patterns: NF/LG, NF/HG, LF/HG, and LF/LG.
Results are expressed as mean ± SD or percentage unless otherwise specified. Data comparisons between patients developing a predefined event and those with no event were performed with Student unpaired t test, chi-square test, or Fisher exact test, as appropriate. Data of the 4 flow-gradient AS groups were compared for statistical significance with 1-way analysis of variance and then with a Tukey test. The BNP levels were compared between groups, due to normality test failure (Kolmogorov-Smirnov), with Kruskal-Wallis 1-way analysis of variance on ranks and then with a Dunn's test.
Probabilities of event-free survival were obtained by Kaplan-Meier estimates for the 4 AS groups and then compared by the use of a 2-sided log-rank test. The impact of group classification on event-free survival was assessed with Cox proportional-hazards models in univariable and multivariable analyses. Variables with a univariable value of p < 0.10 were incorporated into the multivariable models. The selection of variables included in the multivariate model was performed with a special care. To avoid colinearity among a subset of several variables measuring the same phenomenon (e.g., AVA, peak gradient, mean gradient), we entered in the multivariate models the variable that had the strongest association with event-free survival on univariable analysis. The group classification was entered into the model, and patients with NF and LG (i.e., those expected as having the better outcome) were considered as referent. We also built another multivariable model including the risk score (9). Because this score comprises BNP level and peak aortic velocity, these 2 variables were removed from the final statistical model. Values of p < 0.05 were considered statistically significant. All statistical analyses were performed with STATISTICA (version 6, StatSoft Inc., Tulsa, Oklahoma). The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
Characteristics of the patients
Demographic and clinical data are reported in Table 1. On echocardiographic analysis, all patients had moderate-to-severe aortic valve calcification. The mean indexed AVA was 0.5 ± 0.11 cm2/m2. The mean LV outflow tract stroke volume was 85.8 ± 21.5 ml and was widely ranging from 37 to 148 ml. According to the new proposed AS grading classification defined in Methods, NF/HG was found in 78 patients (52%), NF/LG was found in 46 (31%) patients, LF/HG was found in 15 (10%) patients, and LF/LG was found in 11 (7%) patients. Patients with NF/LG had significantly lower BNP than those with LF/HG and LF/LG (Fig. 1) and lower mid-term mortality risk score (Monin et al.  score) than the 3 other groups (Table 2). In addition, patients in NF/HG had significant lower BNP level than those of the LF/HG group (Fig. 1). Demographic, echocardiographic, and clinical characteristics of the 4 groups are reported in Table 2. By design, all patients had a severe AS defined as an AVA <1 cm2 (maximal AVA in each group: NF/LG: 0.98 cm2, NF/HG: 0.97 cm2, LF/HG: 0.96 cm2, and LF/LG: 0.98 cm2).
In the whole cohort, LV global longitudinal strain was negatively correlated with valvulo-arterial impedance (r = −0.23, p = 0.005). This relationship was better in the NF/HG group (r = −0.33, p = 0.004) and in the LF/HG group (r = −0.61, p = 0.017). There was no significant correlation between LVEF and valvulo-arterial impedance in the whole cohort (p = 0.87) or in any AS category (p > 0.50).
The follow-up was complete in all patients (100%). The mean follow-up time was 27 ± 12 months (median: 26 months, range: 2 to 48 months). During follow-up, 76 patients (51%) fulfilled the predefined endpoint, resulting in event-free survival of 71 ± 4%, 51 ± 4%, and 40 ± 5% at 1-, 2- and 3-year follow-up, respectively (Fig. 2). A total of 9 patients died during the follow-up. The cause of death was cardiac in 8 patients. A sudden death occurred in 3 patients who were confirmed to be asymptomatic at the last examination performed within 6 months before death. The reasons for the other 5 cardiac deaths were congestive heart failure. Of note, 2 patients died in the postoperative period of AVR. During follow-up, surgery was indicated in accordance with the guidelines in 70 patients for the following reasons: development of symptoms (n = 58), rapid hemodynamic progression (n = 2), positive exercise test (n = 8), and reduced left ventricular function (n = 2). Three of these patients were awaiting AVR at the time of the current follow-up but were analyzed as patients having undergone AVR.
According to the new proposed AS grading classification, the 2-year cardiac event-free survival was 83 ± 6%, 44 ± 6%, 30 ± 12%, and 27 ± 13% in NF/LG, NF/HG, LF/HG, and LF/LG groups, respectively (p < 0.0001).
Baseline event-free survival predictors
Compared with patients remaining free from event (Table 3), those developing cardiac events had significantly more severe AS and higher valvulo-arterial impedance. They also had statistically higher LV end-diastolic volume, mitral A wave and indexed left atrial (LA) area (p < 0.0001), and lower LV longitudinal strain. By contrast, there was no significant difference between groups for LV end-systolic volume, mass and ejection fraction, mitral E wave, E/A, and E/Ea ratios. Of note, there was no significant difference in event-free survival according to the tertiles of LVEF (tertile 1: 55% to 61%, tertile 2: 62% to 70%, tertile 3: 71% to 85%; p = 0.90).
Univariable Cox proportional hazard model (Table 4) showed that AS severity parameters, valvulo-arterial impedance, LV volumes and longitudinal strain, mitral A wave, indexed LA area, and BNP were significantly associated with event-free survival. In addition, compared with patients with NF/LG (referent), those with LF/LG had a worse outcome (hazard ratio [HR]: 4.54, 95% confidence interval [CI]: 1.99 to 11.1, p = 0.001). Patients with LF/HG also tended to have lower cardiac event-free survival than NF/LG group.
On multivariable analysis, after adjustment for univariable predictive factors, peak aortic velocity (HR: 1.7, 95% CI: 1.04 to 2.84, p = 0.035), LV end-diastolic volume (HR: 1.01, 95% CI: 1.01 to 1.02, p = 0.002), and indexed LA area (HR: 1.13, 95% CI: 1.06 to 1.2, p < 0.0001) were independently associated with event-free survival. Moreover, in the same multivariable model, the new proposed AS grading classification according to flow and gradient was also an independent predictor of event-free survival (p = 0.009) (Fig. 2). The LF/LG (HR: 5.26, 95% CI: 2.04 to 14.3, p = 0.045) and LF/HG (HR: 2.38, 95% CI: 1.02 to 5.55, p = 0.001) were identified as strong independent determinants of poor prognosis as compared with NF/LG (Table 4). Interestingly, when adding the risk score in the model, the new proposed AS grading classification remained independently associated with outcome (p = 0.03). In this model, the risk score was significantly associated with the occurrence of cardiac event (HR: 1.21, 95% CI: 1.05 to 1.4, p = 0.009).
In multivariable analysis, “LF” alone was independently associated with reduced cardiac event-free survival (HR: 1.8, 95% CI: 1.08 to 3.1, p = 0.024). In the same model, excluding “LF” variable, “LG” was also an independent predictor of reduced cardiac event-free survival (HR: 2.4, 95% CI: 1.4 to 4.2, p = 0.003). Finally, when we added the 2 variables in the model, both “LF” and “LG” emerged as independent predictors (HR: 1.7, 95% CI: 1.01 to 2.9, p = 0.046; HR: 2.3, 95% CI: 1.3 to 4.0, p = 0.004, respectively). We also found similar results when the variables were included in a continuous format (i.e., indexed LV stroke volume and mean pressure gradient).
Furthermore, in a multivariable model, limited to patients with LF, LF/LG was an independent predictor of low cardiac event-free survival when compared with LF/HG (HR: 5.4, 95% CI: 1.03 to 28.6, p = 0.046). Similarly, when compared with the NF/HG group (i.e., the more prevalent subgroup of severe AS) in multivariable analysis, LF/LG remained significantly associated with increased risk of cardiac events (HR: 4.3, 95% CI: 2.01 to 13.9, p = 0.001).
Under the terminology of severe AS, several flow-gradient patterns might be identified. The present study shows for the first time that the clinical outcome of truly asymptomatic patients (normal exercise test) with severe AS (AVA <1 cm2) varies noticeably according to these flow-gradient relationships. As compared with the other AS categories, patients with NF/LG have a better cardiac event-free survival. Conversely, both LF/LG and LF/HG entities are associated with a poorer outcome. Finally, patients with NF/HG, the expected pattern for severe AS, present an intermediate prognosis when compared with the other groups.
New proposed AS grading classification and outcome
This pattern is characterized by a lower than expected mean aortic pressure gradient (i.e., <40 mm Hg). In the present study, patients with NF/LG exhibited the best prognosis. This entity is relatively frequent (31%) and characterized by a preserved LV longitudinal myocardial function, resulting in lower BNP level (Fig. 1) and risk score. In this group, the 3-year cardiac event-free survival was 66 ± 9%, which was consistent with the event rate reported in patients with an aortic jet velocity <4.5 m/s (5,8,9). These results suggest that NF/LG pattern identifies a group of patients with a less-severe degree of AS or who has been exposed to the disease for a shorter period of time. Of note, the LA index, a marker reflecting the chronicity of diastolic burden, was lower in these patients. The LA size, when increased, represents a strong independent predictor of outcome in asymptomatic moderate-to-severe AS (8).
This pattern is characterized, as expected, by a mean aortic pressure gradient >40 mm Hg. It represents the most prevalent entity in our series of patients (52%). The 3-year cardiac event-free survival rate of NF/HG, when compared with the NF/LG group, was divided by 2 (66 ± 9% vs. 33 ± 7%). These data suggest that, despite an apparent similar impact of AS on LV longitudinal function and left atrium in both groups (NF/LG and NF/HG), the NF/HG pattern probably corresponds to patients at a more advanced stage of the disease. This assumption is corroborated by the higher BNP level (Fig. 1) and risk score in this category. Furthermore, patients with NF/HG seem to have more severe AS, suggesting a longer exposure to this progressive disease. Given the high prevalence of this entity in asymptomatic severe AS and the relatively high event rate, despite preserved LV systolic function, the management of these patients underlines the need for optimized risk stratification.
In the present study, 15% of our patients had a LF/HG pattern. By definition, these patients have an indexed LV stroke volume <35 ml/m2 in spite of preserved LVEF. In AS, it is well-known that LVEF is a crude estimate of LV systolic function. It might remain normal, despite the presence of reduced LV long-axis function. In asymptomatic patients with AS, impaired subendocardial function has been shown to be associated with impaired exercise tolerance and poor prognosis (12,13). Our results extend these preliminary data (8). A reduction in LV longitudinal deformation was, however, mostly observed in the LF/HG category. Of note, this pattern was also characterized by higher BNP level (Fig. 1) and risk score. As compared with NF/LG, LF/HG was independently associated with a more than 2-fold increased risk of cardiac events. The 3-year cardiac event-free survival was low (20 ± 11%) but nearly identical to that of patients with NF/HG, even though their BNP and risk scores were higher. These data indicate that the LV afterload burden is likely superior to that suggested by the LVEF. In this LF/HG group, the LF state can thus represent a marker of the presence of intrinsic myocardial dysfunction. Careful risk stratification remains the clue in these patients, who deserve an accurate assessment of LV regional function.
An LF/LG pattern was observed in 7% of our patients. It is characterized by a mean aortic pressure gradient <40 mm Hg, an indexed LV stroke volume <35 ml/m2, a preserved LVEF, and an AVA <1 cm2. This pattern, namely paradoxical LF AS, represents a challenging clinical entity that has been recently emphasized. It is associated with more pronounced LV concentric remodeling, smaller LV cavity, increased global LV afterload, intrinsic myocardial dysfunction, and a dismal prognosis (4). Our data are roughly in line with these previous results. The lower prevalence of LF/LG in our series likely relates to the inclusion of patients with a negative exercise test (i.e., “truly” asymptomatic). This LF/LG category displayed the worse outcome. The likelihood of remaining alive without AVR at 3 years was 5-fold lower than for the NF/LG pattern. Furthermore, the risk of cardiac events was 4.3-fold higher in the LF/LG category than in the NF/HG group (i.e., the most prevalent entity of severe AS). The majority of events occurred during the first 24 months. Of note, patients with LF/LG have a cluster of findings, suggesting that they are likely at a more advanced stage of their disease. This LF pattern was in fact associated with higher BNP level and more pronounced impairment of LV longitudinal myocardial function as compared with NF pattern. Interestingly, despite markedly lower event-free survival, patients in LF/LG group exhibit slightly lower BNP and thus risk score than patients with either LF/HG or NF/HG (Fig. 1, Table 2). This observation emphasizes that risk scores might fail to predict the actual risk on an individual basis. Furthermore, our results suggest that the risk score proposed by Monin et al. (9) should be interpreted with caution in patients with LF/LG AS. Conversely, it remains an accurate tool to stratify the risk in the other 3 entities. Of note, in LF/LG AS, the peak aortic jet velocity is by definition reduced (flow-dependent parameter), resulting in a lower risk score, despite elevated BNP levels. This emphasizes the need for further studies aiming at identifying better predictors of outcome of the patients with LF/LG AS. Of note, the relative reduction in BNP level in the LF/LG group might be related to exhausted BNP production (longstanding exposition to the disease), higher BNP clearance, or diminished BNP release secondary to reduced LV wall stress (lower LV volumes than for LF/HG group).
Previous studies have shown that patients with LF/LG are less frequently referred to surgery than those with NF/HG, probably due to underestimation of stenosis severity in light of the relatively low gradient. Hence, failure to recognize this entity can lead to misdiagnosis and inappropriate decision making. The main source of error relates, practically, to the miscalculation of LV stroke volume. In the present study, evidence of an LF state was confirmed by concordant LV stroke volume with both the Doppler and the volumetric methods. Recently, the results of a post-hoc analysis of the Simvastatin and Ezetimibe in Aortic Stenosis trial concerning patients with LG severe AS and moderate AS have been reported (14). Prevalence and outcome of LG and LF/LG significantly differ between our study and the article by Jander et al. (14). Several findings might explain such discrepancies—the most important being the misclassification of the grade of AS. There are several potential causes of discordance between AVA and gradient in patients with preserved LVEF, including: 1) measurement errors; 2) small body size; 3) paradoxical LF AS; and 4) inconsistent grading related to intrinsic discrepancies in guidelines criteria. First, patients with small body size and LV dimensions might exhibit a lower transvalvular pressure gradient, because of a lower albeit normal stroke volume. In contrast to findings of the study by Jander et al. (14) (lower values of body surface area in patients with LG), the body surface area was similar between groups in our population. Second, the stroke volume and therefore the AVA might be underestimated because of underestimation of LV outflow tract and/or misplacement of pulsed-wave Doppler sample volume. In contrast to findings of our data, both the volumetric method and the LV outflow-tract derived stroke volumes were discordant in the study by Jander et al. (14). Moreover, when indexed to body surface area, LV stroke volume indexes were almost similar in both groups (42.1 ml/m2 vs. 42.8 ml/m2), suggesting that a large number of patients with LG severe AS had a stroke volume index >35 ml/m2 and thus an NF. Finally, when AVA was recalculated with the newly obtained LV stroke volume (i.e., derived from the volumetric method), both groups had similar AVA (LG severe AS: 0.99 cm2; moderate AS: 1.01 cm2). These discrepant data and the high rate of misclassifications probably explained the similar outcome between groups in the study of Jander et al. (14).
The results of the present study strengthen the need for a more comprehensive evaluation of AS severity by integrating the flow-gradient pattern into the classic measurement of AVA. Even if they are “really” asymptomatic, the clinical outcomes of these patients vary substantially between categories. The NF/LG pattern was associated with the best prognosis. Of note, no patient of this group died during follow-up. Furthermore, the risk/benefit ratio seems to be largely in favor of treating these patients medically. Conversely, the likelihood of remaining free of events decreased significantly in the 3 other categories—the worse outcome being observed in the LF/LG group. This latter pattern might bring some uncertainty about the actual severity of AS and might lead clinicians to erroneously conclude that the stenosis is not severe and thus to inappropriate delay of follow-up. Practically, these patients deserve closer follow-up (every 6 months) and might benefit from complementary investigation (BNP level monitoring, exercise echocardiography, calcium score measurement). Early elective AVR could represent a beneficial option in those with low comorbidities. Recently, Kang et al. (1) reported that, compared with the conventional approach (i.e., wait for symptoms), early surgery in patients with asymptomatic AS and preserved LVEF was associated with better postoperative LV mass improvement, lower occurrence of postoperative LV dysfunction, and higher long-term survival, essentially by decreasing cardiac mortality (1). Hence, the authors promote early surgery in patients with low operative risk. Indeed, the main concern relates to the possibility of irreversible myocardial damage if inappropriately treated. Patients with an HG pattern displayed an intermediate outcome, regardless of the flow state. However, the LF state represents a witness of intrinsic myocardial dysfunction. Careful assessment of LV function with advanced echocardiographic parameters (i.e., 2-dimensional strain imaging) and appropriate risk stratification is the key in this context. In our study, the values of BNP and risk score are limited, because they can be considered in a “grey zone.” Conversely, exercise echocardiography could potentially be of interest, specifically if it shows a significant rise in mean aortic pressure gradient (15).
The major limitation of the present study relates to the small number of patients in both LF categories, particularly in LF/LG group. This emphasizes the low frequency of such patients in the asymptomatic severe AS population. However, the prevalence of each entity of AS reported in the present study should not be compared with other studies including both asymptomatic and symptomatic patients.
Apparent nonsignificant association between LF groups and echocardiographic or clinical parameters might be related to type II error due to the small sample size. Nonetheless, this limitation does not affect the validity of the main results of this study.
The absence of evaluation of the presence and extent of coronary artery disease in patients not referred to surgery is also a limitation of this report. However, these patients have, by definition, no symptoms and normal LVEF and exercise test. In this context, coronary angiography is not recommended.
The use of the new proposed AS grading classification, integrating valve area and flow-gradient patterns, allows a better characterization of the clinical outcome of patients with asymptomatic severe AS.
Dr. Magne is a research associate from the F.R.S-FNRS, Brussels, Belgium, and received a grant from the Fonds Léon Fredericq, Liège, Belgium. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first 2 authors contributed equally to this work.
- Abbreviations and Acronyms
- aortic stenosis
- aortic valve area
- aortic valve replacement
- B-type natriuretic peptide
- confidence interval
- high gradient
- hazard ratio
- left atrial
- low flow
- low gradient
- left ventricle/ventricular
- left ventricular ejection fraction
- normal flow
- Received May 31, 2011.
- Revision received August 3, 2011.
- Accepted August 9, 2011.
- American College of Cardiology Foundation
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