Kim O'Connor

Clinical Outcome in Asymptomatic Severe Aortic Stenosis Insights From the New Proposed Aortic Stenosis Grading Classification

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/m(2)) 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.

Risk stratification in asymptomatic moderate to severe aortic stenosis: the importance of the valvular, arterial and ventricular interplay

Objective We sought to evaluate prognostic markers of clinical outcome in asymptomatic patients with moderate to severe aortic stenosis (AS). Design Prospective follow-up of asymptomatic patients with moderate to severe AS. The patients underwent clinical and Doppler echocardiographic evaluation. Setting Department of Cardiology. Patients 163 patients with moderate to severe AS (aortic valve area ≤0.6 cm2/m2). Main outcome measures Risk stratification. Predefined endpoints for assessing the outcome were the occurrence during follow-up of symptoms, aortic valve replacement or death. Results During follow-up (mean, 20 (19) months), 11 patients developed symptoms but were not operated on, 57 required aortic valve replacement and six patients died. In multivariable Cox regression analysis, four parameters that were associated with the outcome were identified: peak aortic jet velocity, left ventricular systolic (LV) longitudinal deformation, valvulo-arterial impedance and indexed left atrial area. Using receiver−operator characteristic curve analysis, a peak aortic jet velocity ≥4.4 m/s, a LV longitudinal myocardial deformation ≤15.9%, a valvular-arterial impedance ≥4.9 mm Hg/ml per m2 and an indexed left atrial area ≥12.2 cm2/m2 were identified as the best cut-off values to be associated with events. Conclusions In asymptomatic patients with moderate to severe AS, measurements that integrate the ventricular, vascular and valvular components of the disease improve risk stratification.

Impact of global left ventricular afterload on left ventricular function in asymptomatic severe aortic stenosis: a two-dimensional speckle-tracking study

AIMS The present study sought to assess the effect of global left ventricular (LV) afterload on LV myocardial systolic function in patients with aortic stenosis (AS) and preserved LV ejection fraction. METHODS AND RESULTS We prospectively examined the LV myocardial deformation (i.e. longitudinal, radial, and circumferential) by two-dimensional speckle tracking in 173 patients with asymptomatic severe AS. Thirty-eight patients (22%) had low flow as determined by a low stroke volume index (<or=35 mL/m(2)). By multivariable analysis, four variables emerged as independently associated with low-flow AS: peak Ea velocity (P = 0.01), left atrial area index (P = 0.017), global LV afterload (P = 0.024), and circumferential myocardial deformation (P = 0.04). Forty-nine patients (28%) had an increased global LV afterload (>or=5 mmHg mL/m(2)). Systemic arterial compliance (P = 0.001), circumferential myocardial deformation (P = 0.024), and left atrial area index (P = 0.04) were independently associated with increased global LV load in multivariable analysis. Of note, LV ejection fraction was not identified as a determinant of low flow or increased afterload. CONCLUSION In asymptomatic patients with severe AS, LV ejection fraction markedly underestimates the extent of myocardial systolic impairment. Intrinsic myocardial dysfunction is particularly common in patients with increased global LV afterload, and especially in the subset of patients with low-flow AS.

Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic Stenosis

Background— Recent studies emphasized the usefulness of exercise stress echocardiography in asymptomatic patients with aortic stenosis. Nevertheless, the additive value of exercise pulmonary hypertension (Ex-PHT) in such patients remains unexplored. We therefore aimed to identify the determinants and to test the impact on outcome of Ex-PHT in asymptomatic patients with severe aortic stenosis. Method and Results— Asymptomatic patients with severe aortic stenosis (n=105; aortic valve area <0.6 cm2/m2; age, 71±9 years; male, 59%) and preserved left ventricular systolic function (ejection fraction ≥55%) were prospectively submitted to exercise stress echocardiography. Resting PHT and Ex-PHT were defined as a systolic pulmonary arterial pressure >50 and >60 mm Hg, respectively. Ex-PHT was more frequent than resting PHT (55% versus 6%; P<0.0001). On multivariable logistic regression, the independent predictors of Ex-PHT were male sex (odds ratio, 4.3; P=0.002), resting systolic pulmonary arterial pressure (odds ratio, 1.16; P=0.002), exercise indexed left ventricular end-diastolic volume (odds ratio, 1.04; P=0.026), exercise e′-wave velocity (odds ratio, 1.35; P=0.047), and exercise-induced changes in indexed left atrial area (odds ratio, 1.36; P=0.006). Ex-PHT was associated with reduced cardiac event-free survival (at 3 years, 22±7% versus 55±9%; P=0.014). In a multivariable Cox proportional hazards model, Ex-PHT was identified as an independent predictor of cardiac events (hazard ratio, 1.8; 95% confidence interval, 1.0–3.3; P=0.047). When exercise-induced changes in mean aortic pressure gradient were added to the multivariable model, Ex-PHT remained independently associated with reduced cardiac event-free survival (hazard ratio, 2.0; 95% confidence interval, 1.1–3.6; P=0.025). Conclusions— In asymptomatic patients with severe aortic stenosis, the main determinants of Ex-PHT are male sex, resting systolic pulmonary arterial pressure, and exercise parameters of diastolic burden. Moreover, Ex-PHT is associated with a 2-fold increased risk of cardiac events. These results strongly support the use of exercise stress echocardiography in asymptomatic aortic stenosis.

Prognostic Effect of Long-Axis Left Ventricular Dysfunction and B-Type Natriuretic Peptide Levels in Asymptomatic Aortic Stenosis

In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms. We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events. We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging. B-type natriuretic peptide (BNP) was measured in all patients. During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement. On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012). Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events. In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters.

Impact of aortic stenosis on longitudinal myocardial deformation during exercise

UNLABELLED In aortic stenosis (AS), left ventricular (LV) adaptation to exercise has poorly been examined. Changes in LV ejection fraction may lack accuracy in identifying the presence of intrinsic myocardial impairment. AIMS We sought to determine the impact of aortic stenosis (AS) on left ventricular (LV) longitudinal function at exercise in a series of asymptomatic patients with AS and preserved LV ejection fraction. METHODS AND RESULTS Long-axis function was assessed at rest and at exercise by using 2D speckle tracking of myocardial deformation in 207 AS patients (aortic valve area 0.87 ± 0.19 cm²) and 43 aged-matched control subjects. When compared with control subjects, patients with AS have reduced longitudinal myocardial function at rest (-20.2 ± 2.7 vs. -15.4 ± 4.0%) and at peak exercise (-25.0 ± 3.7 vs. -16.5 ± 4.9%) (P < 0.0001 for both). Exercise changes in global longitudinal strain were correlated with changes in LV ejection in controls but not in patients with AS. Changes in LV global longitudinal strain during test were lower in AS patients with an abnormal response to exercise (-0.5 ± 2.7 vs. -1.5 ± 2.8%, P = 0.001). In multivariate analysis, a lower global longitudinal strain at rest (P = 0.04), a higher increase in mean trans-valvular pressure gradient (P < 0.001) at exercise, and smaller exercise-induced changes in global longitudinal strain (P < 0.001) were associated with an abnormal exercise test. CONCLUSION In AS, subnormal LV function can be reliably identified by 2D strain imaging at rest and during a sub-maximal exercise. That sensitive measure of LV systolic function is depressed in AS and even more in patients having the most severe AS.

Prognostic importance of brain natriuretic peptide and left ventricular longitudinal function in asymptomatic degenerative mitral regurgitation

Objectives To identify the determinants and the impact on outcome of brain natriuretic peptide (BNP) in asymptomatic patients with degenerative mitral regurgitation (MR). Method Comprehensive transthoracic echocardiography including two-dimensional speckle tracking quantification was performed in 135 consecutive asymptomatic patients (60±14 years, 56% men) with moderate to severe degenerative MR and preserved left ventricular (LV) function. Blood samples were collected at the time of the echocardiography and plasma BNP levels were measured. Main outcome measures BNP level and cardiac events. Results BNP was correlated with age, indexed LV end-systolic diameter, indexed left atrium (LA) volume, estimated LV filling pressure with E/Ea ratio, systolic pulmonary arterial pressure and global longitudinal strain (GLS). In multiple regression analysis, indexed LA volume (p=0.008), mitral deceleration time (p=0.003) and GLS (p<0.0001) were independently associated with BNP. During follow-up (mean=23±19 months), 54 events occurred resulting in 4-year event-free survival of 50±6%. There was a graded relationship between the increase in BNP (ie, according to quartile) and reduced event-free survival (p<0.0001). In Cox multivariable analysis, indexed LA volume (HR=1.04, p=0.003), GLS (HR=1.14, p=0.007) and 3rd and 4th quartiles of BNP (HR=8.5, p=0.002 and HR=8.8, p=0.002) were independent determinants of event-free survival. Conclusion In asymptomatic degenerative MR, LV longitudinal function and LA volume are the main determinants of BNP release. BNP is a powerful independent predictor of cardiac events. Measurement of plasma BNP may help to improve risk stratification and management of asymptomatic patients with degenerative MR.

Left atrial function and remodelling in aortic stenosis

AIMS The present study sought to determine the relationship between left atrial (LA) volume (structural changes) and LA function as assessed by strain rate imaging in patients with aortic stenosis (AS). METHODS AND RESULTS The study consisted of a total of 64 consecutive patients with severe AS (<1 cm²) and 20 healthy control subjects. The phasic LA volumes and function (tissue Doppler-derived strain) were assessed in all patients. As compared with healthy controls, all strain-derived parameters of LA function were reduced in patients with AS. Conversely, only indexed LA passive volume (increased) (7.6 ± 3.8 vs. 10.5 ± 5.1 ml/m², P= 0.02) and LA active fraction (decreased) (43 ± 6.7 vs. 31 ± 13.3%, P< 0.001) (volume-based parameters) were significantly different between AS and controls. In AS, LA volume-derived function parameters were poorly correlated with LA strain parameters. In fact, by multivariable analysis, no LA phasic strain parameters emerged as independently associated with LA phasic volume parameters. CONCLUSIONS In AS, changes in LA function did not parallel changes in LA size. Furthermore, the increase in LA volume does not necessarily reflect the presence of intrinsic LA dysfunction.

Impact of aortic valve stenosis on left atrial phasic function.

The aim of this study was to determine the impact of aortic stenosis (AS) on the different components of left atrial (LA) function. The study consisted of a total of 52 consecutive patients with severe AS (aortic valve area < 1 cm(2)) and 20 normal subjects matched for gender, heart rate, body surface area, and baseline systolic blood pressure. Phasic LA longitudinal function was assessed using tissue Doppler imaging. LA peak systolic (reservoir function), early diastolic (conduit function), and late diastolic (active function) strain rates were measured. During late diastole, LA peak strain (active function) was also measured. Mitral annular systolic, early diastolic (Ea), and late diastolic (Aa) velocities were also measured. Compared with controls, all strain values were significantly reduced in patients with AS. By multivariate regression analysis, mitral E-wave deceleration time (p = 0.033) and E/Ea ratio (p = 0.02, R(2) = 0.43) emerged as independently associated with LA peak systolic strain rate. Ea was the sole determinant of LA early diastolic strain rate (p < 0.0001, R(2) = 0.42), whereas LA late diastolic strain rate was independently related to aortic valve area (p = 0.031) and Aa (p = 0.022, R(2) = 0.51). In conclusion, in patients with severe AS, the 3 components of LA function are reduced. LA reservoir dysfunction is related to left ventricular filling pressures, whereas LA conduit dysfunction depends on left ventricular relaxation. Active LA dysfunction is related to the severity of AS and late left ventricular diastolic function.

Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with severe asymptomatic aortic stenosis

Background Exercise-stress echocardiography is useful in management and risk stratification of patients with asymptomatic aortic stenosis (AS). Resting B-type natriuretic peptide (BNP) level is associated with increased risk of adverse events. The incremental prognostic value of BNP response during exercise is unknown. Objective The purpose of this study was to assess the usefulness of plasma level of BNP during exercise to predict occurrence of events in asymptomatic patients with severe AS. Methods Resting and exercise-stress echocardiographic data and plasma BNP levels were prospectively collected in 211 asymptomatic AS patients in whom 157 had severe AS with preserved LVEF in two centres. The study end-point was the occurrence of death or aortic valve replacement. Results Plasma BNP level increased from rest to exercise (p<0.0001). During a mean follow-up of 1.5±1.2 years, 87 patients with severe AS reached the predefined end-point. Higher peak-exercise BNP level was associated with higher occurrence of adverse events (p<0.0001). In multivariate analysis, second and third tertiles of peak-exercise BNP (T2: HR=2.9; p=0.002 and T3: HR=5.3; p<0.0001, respectively) were powerful predictors of events compared with the first tertile. Further adjustment for resting BNP provided comparable results (T2: HR=2.8; p=0.003 and T3: HR=5.0; p<0.0001). This relationship persisted in both subsets of patients with low or high resting BNP. Conclusions This study reports that peak-exercise BNP level provides significant incremental prognostic value beyond what is achieved by demographic and echocardiographic data, as well as resting BNP level.