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Background: Dobutamine stress echocardiography (DSE) is useful to differentiate true from pseudo severe aortic stenosis in patients with low left ventricular ejection fraction (LVEF), low-flow, low-gradient aortic stenosis (LF-LG AS). In the ACC/AHA guidelines, patients are considered having true-severe stenosis when the mean gradient (MG) is ≥40mmHg with an aortic valve area (AVA) ≤1cm2 during DSE. However these criteria have not been previously validated. 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 LFLG AS. Methods: In the TOPAS (“True or Pseudo-Severe Aortic Stenosis”) study, 186 patients with low LVEF LF-LG AS were prospectively recruited and underwent DSE with measurement of the MG, AVA and projected AVA, an estimate of the AVA at a standardized normal flow rate (AVAProj). Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients and by measurement of the aortic valve calcium by computed tomography in 25 patients and by both methods in 8. According to these assessments, 50/87 (57%) of the study cohort had true-severe stenosis. Results: Peak stress MG ≥40 mmHg, peak stress AVA ≤1cm2, and the combination of peak stress MG ≥40 mmHg and peak stress AVA≤1cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1cm2 was better than all the previous markers (p<0.007) with 70% of correct classification. Among the subset of 88 patients managed conservatively (47% of 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 ≤1cm2 was a strong predictor of mortality under medical management (HR: 3.65; p=0.0003). Conclusion: In patients with low LVEF LF-LG AS, the DSE

Background: Dobutamine stress echocardiography (DSE) is useful to differentiate true from pseudo severe aortic stenosis in patients with low left ventricular ejection fraction (LVEF), low-flow, low-gradient aortic stenosis (LF-LG AS). In the ACC/AHA guidelines, patients are considered having true-severe stenosis when the mean gradient (MG) is ≥40mmHg with an aortic valve area (AVA) ≤1cm2 during DSE. However these criteria have not been previously validated. 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 LFLG AS. Methods: In the TOPAS (“True or Pseudo-Severe Aortic Stenosis”) study, 186 patients with low LVEF LF-LG AS were prospectively recruited and underwent DSE with measurement of the MG, AVA and projected AVA, an estimate of the AVA at a standardized normal flow rate (AVAProj). Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients and by measurement of the aortic valve calcium by computed tomography in 25 patients and by both methods in 8. According to these assessments, 50/87 (57%) of the study cohort had true-severe stenosis. Results: Peak stress MG ≥40 mmHg, peak stress AVA ≤1cm2, and the combination of peak stress MG ≥40 mmHg and peak stress AVA≤1cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1cm2 was better than all the previous markers (p<0.007) with 70% of correct classification. Among the subset of 88 patients managed conservatively (47% of 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 ≤1cm2 was a strong predictor of mortality under medical management (HR: 3.65; p=0.0003). Conclusion: In patients with low LVEF LF-LG AS, the DSE

BACKGROUND: The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome. METHODS AND RESULTS: BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left ventricular ejection fraction < or = 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50, P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42, P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13% versus 92+/-7%). CONCLUSIONS: BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.

Objectives : This study sought to examine the impact of tricuspid regurgitation (TR) on mortality in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF). Background : TR is often observed in patients with LF-LG AS and low LVEF, but its impact on prognosis remains unknown. Methods : A total of 211 patients (73 ± 10 years of age; 77% men) with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area [AVA] =0.6 cm2/m2) and reduced LVEF (=40%) were prospectively enrolled in the TOPAS (True or Pseudo-Severe Aortic Stenosis) study and 125 (59%) of them underwent aortic valve replacement (AVR) within 3 months following inclusion. The severity of AS was assessed by the projected AVA (AVAproj) at normal flow rate (250 ml/s), as previously described and validated. The severity of TR was graded according to current guidelines. Results : Among the 211 patients included in the study, 22 (10%) had no TR, 113 (54%) had mild (grade 1), 50 (24%) mild-to-moderate (grade 2), and 26 (12%) moderate-to-severe (grade 3) or severe (grade 4) TR. During a mean follow-up of 2.4 ± 2.2 years, 104 patients (49%) died. Univariable analysis showed that TR =2 was associated with increased risk of all-cause mortality (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.22 to 2.71; p = 0.004) and cardiovascular mortality (HR: 1.85, 95% CI: 1.20 to 2.83; p = 0.005). After adjustment for age, sex, coronary artery disease, AVAproj, LVEF, stroke volume index, right ventricular dysfunction, mitral regurgitation, and type of treatment (AVR vs. conservative), the presence of TR =2 was an independent predictor of all-cause mortality (HR: 1.88, 95% CI: 1.08 to 3.23; p = 0.02) and cardiovascular mortality (HR: 1.92, 95% CI: 1.05 to 3.51; p = 0.03). Furthermore, in patients undergoing AVR, TR =3 was an independent predictor of 30-day mortality compared with TR = 0/1 (odds ratio [OR]: 7.24, 95% CI: 1.56 to 38.2; p = 0.01) and TR = 2

Background— We sought to investigate the use of a new parameter, the projected effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. Methods and Results— The use of EOAproj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection fraction =40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOAproj was calculated as EOAproj=EOArest+VC×(250-Qrest), where EOArest and Qrest are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOAproj and 91% for indexed EOAproj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. Conclusions— EOAproj provides a standardized evaluation of AS severity with DSE and improves the diagnostic accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient AS.

BACKGROUND: Impairment of myocardial flow reserve (MFR) in aortic stenosis (AS) with normal left ventricular function relates to the haemodynamic severity. OBJECTIVES: To investigate whether myocardial blood flow (MBF) and MFR differ in low-flow, low-gradient AS depending on whether there is underlying true-severe AS (TSAS) or pseudo-severe AS (PSAS). METHODS: In 36 patients with low-flow, low-gradient AS, dynamic [13N]ammonia PET perfusion imaging was performed at rest (n = 36) and during dipyridamole stress (n = 20) to quantify MBF and MFR. Dobutamine echocardiography was used to classify patients as TSAS (n = 18) or PSAS (n = 18) based on the indexed projected effective orifice area (EOA) at a normal flow rate of 250 ml/s (EOAI(proj )0.55 cm(2)/m(2)). RESULTS: Compared with healthy controls (n = 14), patients with low-flow, low-gradient AS had higher resting mean (SD) MBF (0.83 (0.21) vs 0.69 (0.09) ml/min/g, p = 0.001), reduced hyperaemic MBF (1.16 (0.31) vs 2.71 (0.50) ml/min/g, p<0.001) and impaired MFR (1.44 (0.44) vs 4.00 (0.91), p<0.001). Resting MBF and MFR correlated with indices of AS severity in low-flow, low-gradient AS with the strongest relationship observed for EOAI(proj) (r(s) = -0.50, p = 0.002 and r(s) = 0.61, p = 0.004, respectively). Compared with PSAS, TSAS had a trend to a higher resting MBF (0.90 (0.19) vs 0.77 (0.21) ml/min/g, p = 0.06), similar hyperaemic MBF (1.16 (0.31) vs 1.17 (0.32) ml/min/g, p = NS), but a significantly smaller MFR (1.19 (0.26) vs 1.76 (0.41), p = 0.003). An MFR <1.8 had an accuracy of 85% for distinguishing TSAS from PSAS. CONCLUSIONS: Low-flow, low-gradient AS is characterised by higher resting MBF and reduced MFR that relates to the AS severity. The degree of MFR impairment differs between TSAS and PSAS and may be of value for distinguishing these entities.

Background— Patients with low-flow, low-gradient aortic stenosis have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Recently, we proposed a new index of aortic stenosis severity derived from dobutamine stress echocardiography, the projected aortic valve area at a normal transvalvular flow rate, as superior to other conventional indices to differentiate true-severe from pseudosevere aortic stenosis. The objective of this study was to identify the determinants of survival, functional status, and change in left ventricular ejection fraction during follow-up of patients with low-flow, low-gradient aortic stenosis. Methods and Results— One hundred one patients with low-flow, low-gradient aortic stenosis (aortic valve area ≤1.2 cm2, left ventricular ejection fraction ≤40%, and mean gradient ≤40 mm Hg) underwent dobutamine stress echocardiography and an assessment of functional capacity using the Duke Activity Status Index. A subset of 72 patients also underwent a 6-minute walk test. Overall survival was 70±5% at 1 year and 57±6% at 3 years. After adjusting for age, gender, and the type of treatment (aortic valve replacement versus no aortic valve replacement), significant predictors of mortality during follow-up were a Duke Activity Status Index ≤20 (P=0.0005) or 6-minute walk test distance ≤320 m (P<0.0001, in the subset of 72 patients), projected aortic valve area at a normal transvalvular flow rate ≤1.2 cm2 (P=0.03), and peak dobutamine stress echocardiography left ventricular ejection fraction ≤35% (P=0.03). More severe stenosis, defined as projected aortic valve area ≤1.2 cm2, was a predictor of mortality only in the no aortic valve replacement group. The Duke Activity Status Index, 6-minute walk test, and left ventricular ejection fraction improved significantly during follow-up in the aortic valve replacement group, but remained unchanged or decreased in the no aortic valve replacement group. Conclusion— In patient

Background—Patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically. Recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients considered at high or prohibitive operative risk. The objective of this study was to compare TAVI and SAVR with respect to postoperative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function.Methods and Results—Echocardiographic data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area =1 cm2) with reduced LV systolic function (LVEF =50%). TAVI patients were significantly older (81±8 versus 70±10 years; P<0.0001) and had more comorbidities compared with SAVR patients. Despite similar baseline LVEF (34±11% versus 34±10%), TAVI patients had better recovery of LVEF compared with SAVR patients (¿LVEF, 14±15% versus 7±11%; P=0.005). At the 1-year follow-up, 58% of TAVI patients had a normalization of LVEF (>50%) as opposed to 20% in the SAVR group. On multivariable analysis, female gender (P=0.004), lower LVEF at baseline (P=0.005), absence of atrial fibrillation (P=0.01), TAVI (P=0.007), and larger increase in aortic valve area after the procedure (P=0.01) were independently associated with better recovery of LVEF. Conclusion—In patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR. TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

Background : It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVAproj), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVAproj in a large series of patients and to propose a new clinically applicable simplified method to estimate AVAproj. Methods : AVAproj was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVAproj = AVArest + slope × (250 - Qrest). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q. Results : There was a strong correlation between AVAproj calculated by the two methods (r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVAproj demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVAproj = 1 cm2, 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVAproj correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVAproj = 1.2 cm2 (hazard ratio, 1.65; P = .02) and sim

Background— Decision making in patients with low flow–low gradient aortic stenosis mainly depends on the actual stenosis severity and left ventricular function, which is of prognostic importance. We used 2-dimensional strain parameters measured by speckle tracking at rest and during dobutamine stress echocardiography to document the extent of myocardial impairment, its relationship with hemodynamic variables, and its prognostic value. Methods and Results— In 47 patients with low flow–low gradient aortic stenosis, global peak systolic longitudinal strain (PLS) and peak systolic longitudinal strain rate (PLSR) were analyzed. PLS and PLSR at rest and peak stress were −7.56±2.34% and −7.41±2.89% (P=NS) and −0.38±0.12 s−1 and −0.53±0.18 s−1 (P<0.001), respectively. PLS and PLSR inversely correlated with left ventricular ejection fraction at rest (rs=−0.52; P<0.0001 and −0.38; P=0.008) and peak stress (rs=−0.39; P=0.007 and −0.45; P=0.002). The overall 2-year survival rate was 60%. Univariate predictors of survival were peak stress left ventricular ejection fraction (P=0.0026), peak stress PLS (P=0.0002), peak stress PLSR (P<0.0001), and N-terminal pro–B-type natriuretic peptide (P<0.0001). Three hierarchically nested multivariable Cox regression models were constructed—model 1: The Society of Thoracic Surgeons score as an indicator of clinical risk (area under the receiver operating characteristic=0.59); model 2: model 1+N-terminal pro–B-type natriuretic peptide and peak stress left ventricular ejection fraction (area under the receiver operating characteristic=0.83; incremental P<0.0001); model 3: model 2+peak stress PLSR (area under the receiver operating characteristic=0.89; incremental P=0.035). Conclusions— In patients with low flow–low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak stress PLSR may add incremental prognostic value beyond what is obtained from N-terminal pro–B-type natriuretic peptide and peak stress

Background — The objective of this study was to examine the impact of left ventricular (LV) global longitudinal strain (GLS) measured at rest and at dobutamine stress echocardiography on the outcome of patients with low LV ejection fraction and low-gradient aortic stenosis. Methods and Results — Among the 202 patients with low LV ejection fraction (=40%), low-gradient aortic stenosis (mean transvalvular gradient <40 mm¿Hg and indexed aortic valve area =0.6 cm2/m2) prospectively enrolled in the multicenter True or Pseudo-Severe Aortic Stenosis study, 126 patients with resting GLS and 73 patients with stress GLS available were included in this substudy. Three-year survival rate was 49% in patients with rest GLS <|9|% compared with 68% in patients with GLS >|9|% (P=0.02). In a multivariable Cox model adjusted for age, coronary artery disease, projected aortic valve area at a normal flow rate and type of treatment (aortic valve replacement versus conservative), rest GLS <|9|% (hazard ratio, 2.18; P=0.015) remained independently associated with all-cause mortality. GLS <|10|% measured during dobutamine stress echocardiography was also independently associated with mortality (hazard ratio, 2.67; P=0.01). In the subset of patients with stress GLS (n=73), the ¿2 of the multivariable model to predict all-causes mortality was 21.96 for stress GLS versus 17.78 for rest GLS. Conclusions — GLS is independently associated with mortality in patients with low LV ejection fraction, low-gradient aortic stenosis. Stress GLS measured during dobutamine stress echocardiography may provide incremental prognostic value beyond GLS measured at rest. Hence, measurement of GLS at rest and during dobutamine stress echocardiography may be helpful to enhance risk stratification in low LV ejection fraction, low-gradient aortic stenosis.

Background — The objective of this study was to examine the impact of left ventricular (LV) global longitudinal strain (GLS) measured at rest and at dobutamine stress echocardiography on the outcome of patients with low LV ejection fraction and low-gradient aortic stenosis. Methods and Results — Among the 202 patients with low LV ejection fraction (=40%), low-gradient aortic stenosis (mean transvalvular gradient <40 mm¿Hg and indexed aortic valve area =0.6 cm2/m2) prospectively enrolled in the multicenter True or Pseudo-Severe Aortic Stenosis study, 126 patients with resting GLS and 73 patients with stress GLS available were included in this substudy. Three-year survival rate was 49% in patients with rest GLS <|9|% compared with 68% in patients with GLS >|9|% (P=0.02). In a multivariable Cox model adjusted for age, coronary artery disease, projected aortic valve area at a normal flow rate and type of treatment (aortic valve replacement versus conservative), rest GLS <|9|% (hazard ratio, 2.18; P=0.015) remained independently associated with all-cause mortality. GLS <|10|% measured during dobutamine stress echocardiography was also independently associated with mortality (hazard ratio, 2.67; P=0.01). In the subset of patients with stress GLS (n=73), the ¿2 of the multivariable model to predict all-causes mortality was 21.96 for stress GLS versus 17.78 for rest GLS. Conclusions — GLS is independently associated with mortality in patients with low LV ejection fraction, low-gradient aortic stenosis. Stress GLS measured during dobutamine stress echocardiography may provide incremental prognostic value beyond GLS measured at rest. Hence, measurement of GLS at rest and during dobutamine stress echocardiography may be helpful to enhance risk stratification in low LV ejection fraction, low-gradient aortic stenosis.

Background—Decision making in patients with low flow–low gradient aortic stenosis mainly depends on the actual stenosis severity and left ventricular function, which is of prognostic importance. We used 2-dimensional strain parameters measured by speckle tracking at rest and during dobutamine stress echocardiography to document the extent of myocardial impairment, its relationship with hemodynamic variables, and its prognostic value. Methods and Results—In 47 patients with low flow–low gradient aortic stenosis, global peak systolic longitudinal strain (PLS) and peak systolic longitudinal strain rate (PLSR) were analyzed. PLS and PLSR at rest and peak stress were -7.56±2.34% and -7.41±2.89% (P=NS) and -0.38±0.12 s-1 and -0.53±0.18 s-1 (P<0.001), respectively. PLS and PLSR inversely correlated with left ventricular ejection fraction at rest (rs =-0.52; P<0.0001 and -0.38; P=0.008) and peak stress (rs =-0.39; P=0.007 and -0.45; P=0.002). The overall 2-year survival rate was 60%. Univariate predictors of survival were peak stress left ventricular ejection fraction (P=0.0026), peak stress PLS (P=0.0002), peak stress PLSR (P<0.0001), and N-terminal pro–B-type natriuretic peptide (P<0.0001). Three hierarchically nested multivariable Cox regression models were constructed—model 1: The Society of Thoracic Surgeons score as an indicator of clinical risk (area under the receiver operating characteristic=0.59); model 2: model 1+N-terminal pro–B-type natriuretic peptide and peak stress left ventricular ejection fraction (area under the receiver operating characteristic=0.83; incremental P<0.0001); model 3: model 2+peak stress PLSR (area under the receiver operating characteristic=0.89; incremental P=0.035). Conclusions—In patients with low flow–low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak stress PLSR may add incremental prognostic value beyond what is obtained from N-terminal pro–B-type natriuretic peptide and peak stress l

Background—Patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically. Recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients considered at high or prohibitive operative risk. The objective of this study was to compare TAVI and SAVR with respect to postoperative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function.Methods and Results—Echocardiographic data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area =1 cm2) with reduced LV systolic function (LVEF =50%). TAVI patients were significantly older (81±8 versus 70±10 years; P<0.0001) and had more comorbidities compared with SAVR patients. Despite similar baseline LVEF (34±11% versus 34±10%), TAVI patients had better recovery of LVEF compared with SAVR patients (¿LVEF, 14±15% versus 7±11%; P=0.005). At the 1-year follow-up, 58% of TAVI patients had a normalization of LVEF (>50%) as opposed to 20% in the SAVR group. On multivariable analysis, female gender (P=0.004), lower LVEF at baseline (P=0.005), absence of atrial fibrillation (P=0.01), TAVI (P=0.007), and larger increase in aortic valve area after the procedure (P=0.01) were independently associated with better recovery of LVEF. Conclusion—In patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR. TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

BACKGROUND: Impairment of myocardial flow reserve (MFR) in aortic stenosis (AS) with normal left ventricular function relates to the haemodynamic severity. OBJECTIVES: To investigate whether myocardial blood flow (MBF) and MFR differ in low-flow, low-gradient AS depending on whether there is underlying true-severe AS (TSAS) or pseudo-severe AS (PSAS). METHODS: In 36 patients with low-flow, low-gradient AS, dynamic [13N]ammonia PET perfusion imaging was performed at rest (n = 36) and during dipyridamole stress (n = 20) to quantify MBF and MFR. Dobutamine echocardiography was used to classify patients as TSAS (n = 18) or PSAS (n = 18) based on the indexed projected effective orifice area (EOA) at a normal flow rate of 250 ml/s (EOAI(proj )0.55 cm(2)/m(2)). RESULTS: Compared with healthy controls (n = 14), patients with low-flow, low-gradient AS had higher resting mean (SD) MBF (0.83 (0.21) vs 0.69 (0.09) ml/min/g, p = 0.001), reduced hyperaemic MBF (1.16 (0.31) vs 2.71 (0.50) ml/min/g, p<0.001) and impaired MFR (1.44 (0.44) vs 4.00 (0.91), p<0.001). Resting MBF and MFR correlated with indices of AS severity in low-flow, low-gradient AS with the strongest relationship observed for EOAI(proj) (r(s) = -0.50, p = 0.002 and r(s) = 0.61, p = 0.004, respectively). Compared with PSAS, TSAS had a trend to a higher resting MBF (0.90 (0.19) vs 0.77 (0.21) ml/min/g, p = 0.06), similar hyperaemic MBF (1.16 (0.31) vs 1.17 (0.32) ml/min/g, p = NS), but a significantly smaller MFR (1.19 (0.26) vs 1.76 (0.41), p = 0.003). An MFR <1.8 had an accuracy of 85% for distinguishing TSAS from PSAS. CONCLUSIONS: Low-flow, low-gradient AS is characterised by higher resting MBF and reduced MFR that relates to the AS severity. The degree of MFR impairment differs between TSAS and PSAS and may be of value for distinguishing these entities.

Background—Patients with low-flow, low-gradient aortic stenosis have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Recently, we proposed a new index of aortic stenosis severity derived from dobutamine stress echocardiography, the projected aortic valve area at a normal transvalvular flow rate, as superior to other conventional indices to differentiate true-severe from pseudosevere aortic stenosis. The objective of this study was to identify the determinants of survival, functional status, and change in left ventricular ejection fraction during follow-up of patients with low-flow, low-gradient aortic stenosis. Methods and Results—One hundred one patients with low-flow, low-gradient aortic stenosis (aortic valve area 1.2 cm2 , left ventricular ejection fraction 40%, and mean gradient 40 mm Hg) underwent dobutamine stress echocardiography and an assessment of functional capacity using the Duke Activity Status Index. A subset of 72 patients also underwent a 6-minute walk test. Overall survival was 70 5% at 1 year and 57 6% at 3 years. After adjusting for age, gender, and the type of treatment (aortic valve replacement versus no aortic valve replacement), significant predictors of mortality during follow-up were a Duke Activity Status Index 20 (P0.0005) or 6-minute walk test distance 320 m (P0.0001, in the subset of 72 patients), projected aortic valve area at a normal transvalvular flow rate 1.2 cm2 (P0.03), and peak dobutamine stress echocardiography left ventricular ejection fraction 35% (P0.03). More severe stenosis, defined as projected aortic valve area 1.2 cm2 , was a predictor of mortality only in the no aortic valve replacement group. The Duke Activity Status Index, 6-minute walk test, and left ventricular ejection fraction improved significantly during follow-up in the aortic valve replacement group, but remained unchanged or decreased in the no aortic valve replacement group. Conclusion—In patients with low-fl

BACKGROUND: The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome. METHODS AND RESULTS: BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left ventricular ejection fraction < or = 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50, P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42, P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13% versus 92+/-7%). CONCLUSIONS: BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.

Background— We sought to investigate the use of a new parameter, the projected effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. Methods and Results— The use of EOAproj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection fraction =40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOAproj was calculated as EOAproj=EOArest+VC×(250-Qrest), where EOArest and Qrest are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOAproj and 91% for indexed EOAproj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. Conclusions— EOAproj provides a standardized evaluation of AS severity with DSE and improves the diagnostic accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient AS.