Search

Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin-angiotensin-aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era., Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database., Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018., Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations., Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients)., Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients.

Aims: The objective assessment of maximal exercise capacity (MEC) using peak oxygen consumption (VO2) measurement may be helpful in the management of asymptomatic aortic stenosis (AS) patients. However, the relationship between left ventricular (LV) function and MEC has been relatively unexplored. We aimed to identify which echocardiographic parameters of LV systolic function can predict MEC in asymptomatic AS., Methods and Results: Asymptomatic patients with moderate to severe AS (n = 44, aortic valve area <1.5 cm(2), 66 ± 13 years, 75% of men) and preserved LV ejection fraction (LVEF > 50%) were prospectively referred for resting echocardiography and cardiopulmonary exercise test. LV longitudinal strain (LS) of each myocardial segment was measured by speckle tracking echocardiography (STE) from the apical (aLS) 4-, 2-, and 3-chamber views. An average value of the LS of the analysable segments was provided for each myocardial region: basal (bLS), mid (mLS), and aLS. LV circumferential and radial strains were measured from short-axis views. Peak VO2 was 20.1 ± 5.8 mL/kg/min (median 20.7 mL/kg/min; range 7.2-32.3 mL/kg/min). According to the median of peak VO2, patients with reduced MEC were significantly older (P < 0.001) and more frequently females (P = 0.05). There were significant correlations between peak VO2 and age (r = -0.44), LV end-diastolic volume (r = 0.35), LV stroke volume (r = 0.37), indexed stroke volume (r = 0.32), and E/e' ratio (r = -0.37, all P < 0.04). Parameters of AS severity and LVEF did not correlate with peak VO2 (P = NS for all). Among LV deformation parameters, bLS and mLS were significantly associated with peakVO2 (r = 0.43, P = 0.005, and r = 0.32, P = 0.04, respectively). With multivariable analysis, female gender (β = 4.9; P = 0.008) and bLS (β = 0.50; P = 0.03) were the only independent determinants (r(2) = 0.423) of peak VO2., Conclusion: In asymptomatic AS, impaired LV myocardial longitudinal function determines reduced MEC. Basal LS was the only parameter of LV regional function independently associated with MEC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with ≥ moderate aortic stenosis (AS) and preserved left ventricular ejection fraction., Methods: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death., Results: During a follow-up of 30 ± 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 ± 9 vs 65 ± 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 ± 0.6 vs 3.5 ± 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 ± 2.5 vs 8.7 ± 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 ± 155 vs +7 ± 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 ± 8% vs 97 ± 3%; 3 years: 31 ± 8% vs 68 ± 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters., Conclusions: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Degenerative aortic stenosis (AS) is one of the most frequent valvular heart diseases in Western countries. Echocardiography plays a central role in the evaluation and management of patients with AS. To overcome the inherent inconsistencies between the echocardiographic parameters defining severe AS and to unify concepts, a new classification based on the interplay between flow and gradients has recently been adopted. Outcome studies of asymptomatic patients with preserved left ventricular ejection fraction (LVEF), as classified by this new approach, have shown that low-flow (LF) states are associated with poor outcome, that the classical normal-flow/high-gradient pattern has an intermediate outcome, while normal-flow/low-gradient severe AS seems to have an outcome comparable to moderate AS and such patients do not benefit from aortic valve replacement. Patients with LF/low-gradient severe AS with preserved LVEF, also known as "paradoxical LF/low-gradient AS," have the worst outcome and benefit greatly from surgical or percutaneous valve replacement, provided that severity is proven. In patients with LF/low-gradient and depressed LVEF, dobutamine stress echocardiography has an important role to distinguish severe from pseudo-severe AS and to assess surgical risk. Assessment of aortic valve calcium score, as well as computation of projected effective orifice aortic area at normal trans-valvular flow rates, has proved to be very useful to distinguish severe from pseudo-severe AS in LF/low-gradient AS with both reduced and preserved LVEF. Asymptomatic patients with normal flow/gradient should be submitted to an exercise test; exercise echocardiography can identify patients at increased risk when mean gradient increases by >18-20 mmHg and/or pulmonary arterial hypertension develops during exercise.

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.

B-type natriuretic peptide (BNP) level may be a useful prognostic marker for the management of asymptomatic patients with aortic stenosis (AS). The aim of this study was to identify the echocardiographic determinants of BNP changes during follow-up in AS. We studied 61 asymptomatic patients with greater than moderate AS and preserved left ventricular (LV) ejection fraction who underwent rest and exercise Doppler echocardiography with concomitant BNP level measurement at baseline. BNP measurement was repeated after inclusion every 6 months. Patients were divided into 2 groups according to the median of BNP changes during follow-up. According to parameters at rest, patients in the high BNP changes group had significantly higher E/e' ratio. Statistically significant correlations were found between BNP changes and E/e' ratio and indexed left atrial area. According to exercise parameters, patients in the high BNP changes group had significantly lower exercise-induced increase in LV ejection fraction. Statistically significant correlations were found between BNP changes and exercise-induced changes in LV ejection fraction. After adjustment for age, mean aortic pressure gradient, and BNP level at baseline, multivariate analysis identified indexed left atrial area, E/e' at rest, and exercise-induced increase in ejection fraction as independent determinants of BNP changes during follow-up. In conclusion, this study shows that, in asymptomatic patients with preserved LV function and moderate AS, serial BNP measurements may widely vary. Subclinical LV diastolic and systolic dysfunctions are frequently present in patients with higher serial BNP changes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The determinants of maximal exercise capacity (MEC) in aortic stenosis (AS) are, in large part, unknown. We hypothesized that the left ventricular (LV) global hemodynamic load--as assessed by the valvulo-arterial impedance (Zva)--is one of the main determinants of MEC and we sought to evaluate the factors associated with reduced MEC in AS., Method and Results: Asymptomatic patients with moderate or severe AS (n=62, aortic valve area <1.5 cm(2), 65 ± 13 years, 68% men) and preserved LV systolic function (ejection fraction>50%) were prospectively referred for comprehensive resting echocardiography and cardiopulmonary exercise test. Absolute peak VO2 was 19.5 ± 5.7 mL/kg/min (median 19.6 mL/kg/min; range 7.2-33.1 mL/kg/min). There were significant correlations between peak VO2 and: age, body mass index, LV stroke volumes, cardiac output, mean flow rate, mitral annulus s' and e' wave velocities, E/e' ratio and left atrial diameter (all p<0.05). Indexed mean flow rate and Zva were the strongest univariable echocardiographic determinants of peak VO2 (r=0.44, p<0.001 and r=-0.39, p=0.002, respectively). In addition, patients with reduced MEC (peak VO2

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 cm(2)/m(2); 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.

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 < or =0.6 cm(2)/m(2))., 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 > or =4.4 m/s, a LV longitudinal myocardial deformation < or =15.9%, a valvular-arterial impedance > or =4.9 mm Hg/ml per m(2) and an indexed left atrial area > or =12.2 cm(2)/m(2) 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.

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=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.

Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population.

Background: In patients with asymptomatic valvular aortic stenosis, exercise testing may help to stratify the clinical risk. However, data are limited, and the role of quantitative exercise Doppler echocardiography has never been investigated., Methods and Results: Sixty-nine consecutive patients with severe asymptomatic aortic stenosis (aortic valve area <1 cm2) who prospectively underwent quantitative Doppler echocardiographic measurements at rest and during semisupine exercise test were followed up for 15+/-7 months. Of these, 26 had an abnormal response to exercise [occurrence of > or =1 of the following findings: angina, dyspnea, > or =2 mm ST segment depression, or fall or small (<20 mm Hg) rise in systolic blood pressure during the test] and 18 presented cardiac events during follow-up (symptoms in 2 patients, acute pulmonary edema in 2, aortic valve replacement in 12, and cardiac death in 2). In univariate analysis, patients who had cardiac events exhibited a higher increase in both peak (29+/-16 versus 22+/-14 mm Hg; P=0.019) and mean (23+/-8 versus 12+/-7 mm Hg; P=0.000003) transvalvular pressure gradients, whereas the left ventricular ejection fraction reached at peak stress was lower. These patients experienced more frequently symptoms during exercise (14 of 18 versus 12 of 51; P=0.0008). By multivariate Cox regression analysis, independent predictors of cardiac events were as follows: an increase in mean transaortic pressure gradient by > or =18 mm Hg during exercise (P=0.0015), an abnormal exercise test (P=0.0026), and an aortic valve area <0.75 cm2 (P=0.0031). Exercise Doppler echocardiographic findings provided incremental prognostic value over resting echocardiographic and exercise electrocardiographic parameters., Conclusions: Quantitative Doppler exercise echocardiography could be useful to identify a high-risk subset of patients with asymptomatic valvular aortic stenosis and help for clinical decision making.