Impact of chronic obstructive pulmonary disease on right ventricular function and remodeling after aortic valve replacement.

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and right ventricular (RV) dysfunction are common factors that have been associated with poor prognosis after aortic valve replacement (AVR). Since there is still uncertainty about the impact of COPD on RV function and dilatation in patients undergoing AVR, we sought to explore RV function and remodeling in the presence and absence of COPD as well as their prognostic implications. METHODS: Patients who received surgical or transcatheter AVR due to severe AS were screened for COPD. Demographic and clinical data were collected at baseline while echocardiographic measurements were performed at baseline and 1 year after AVR. The study end-point was all-cause mortality. RESULTS: In total 275 patients were included, with 90 (33%) patients having COPD. At 1-year follow-up, mild worsening of tricuspid annular planar systolic excursion and RV dilatation were observed in patients without COPD, while there were significant improvements in RV longitudinal strain, RV wall thickness but dilatation of RV outflow tract distal dimension in the COPD group compared to the baseline. On multivariable analysis, the presence of COPD provided significant incremental prognostic value over RV dysfunction and remodeling. CONCLUSIONS: At 1-year after AVR, RV function and dimensions mildly deteriorated in non-COPD group whereas COPD group received significant benefit of AVR in terms of RV function and hypertrophy. COPD was independently associated with >2-fold all-cause mortality and had incremental prognostic value over RV dysfunction and remodeling.

Changes in Computed-Tomography-Derived Segmental Left Ventricular Longitudinal Strain After Transcatheter Aortic Valve Implantation.

Patients with severe aortic stenosis (AS) may show left ventricular (LV) apical longitudinal strain sparing. Transcatheter aortic valve implantation (TAVI) improves LV systolic function in patients with severe AS. However, the changes in regional longitudinal strain after TAVI have not been extensively evaluated. This study aimed to characterize the effect of the pressure overload relief after TAVI on LV apical longitudinal strain sparing. A total of 156 patients (mean age 80 ± 7 years, 53% men) with severe AS who underwent computed tomography before and within 1 year after TAVI (mean time to follow-up 50 ± 30 days) were included. LV global and segmental longitudinal strain were assessed using feature tracking computed tomography. LV apical longitudinal strain sparing was evaluated as the ratio between the apical and midbasal longitudinal strain and was defined as an LV apical to midbasal longitudinal strain ratio >1. LV apical longitudinal strain remained stable after TAVI (from 19.5 ± 7.2% to 18.7 ± 7.7%, p = 0.20), whereas LV midbasal longitudinal strain showed a significant increase (from 12.9 ± 4.2% to 14.2 ± 4.0%, p ≤0.001). Before TAVI, 88% of the patients presented with LV apical strain ratio >1% and 19% presented with an LV apical strain ratio >2. After TAVI, these percentages significantly decreased to 77% and 5% (p = 0.009, p ≤0.001), respectively. In conclusion, LV apical sparing of strain is a relatively common finding in patients with severe AS who underwent TAVI and its prevalence decreases after the afterload relief after TAVI.

The impact of atrial fibrillation on prognosis in aortic stenosis.

BACKGROUND: Atrial fibrillation (AF) and aortic stenosis (AS) are both highly prevalent and often coexist. Various studies have focused on the prognostic value of AF in patients with AS, but rarely considered left ventricular (LV) diastolic function as a prognostic factor. OBJECTIVE: To evaluate the prognostic impact of AF in patients with AS while correcting for LV diastolic function. METHODS: Patients with first diagnosis of significant AS were selected and stratified according to history of AF. The endpoint was all-cause mortality. RESULTS: In total, 2849 patients with significant AS (mean age 72 ± 12 years, 54.8% men) were evaluated, and 686 (24.1%) had a history of AF. During a median follow-up of 60 (30-97) months, 1182 (41.5%) patients died. Ten-year mortality rate in patients with AF was 46.8% compared to 36.8% in patients with sinus rhythm (SR) (log-rank P < 0.001). On univariable (HR: 1.42; 95% CI: 1.25-1.62; P < 0.001) and multivariable Cox regression analysis (HR: 1.19; 95% CI: 1.02-1.38; P = 0.026), AF was independently associated with mortality. However, when correcting for indexed left atrial volume, E/e' or both, AF was no longer independently associated with all-cause mortality. CONCLUSION: Patients with significant AS and AF have a reduced survival as compared to patients with SR. Nonetheless, when correcting for markers of LV diastolic function, AF was not independently associated with outcomes in patients with significant AS.

Association Between Chronic Obstructive Pulmonary Disease and All-Cause Mortality After Aortic Valve Replacement for Aortic Stenosis.

Chronic obstructive pulmonary disease (COPD) and aortic stenosis (AS) are the most common diseases in which age plays a major role in the increase of their prevalence and when they co-exist, the outcomes prognosis worsens significantly. The aim of the present study was to evaluate the association between pulmonary functional parameters and all-cause mortality after aortic valve replacement (transcatheter or surgical). A total of 400 patients with severe AS and preoperative pulmonary functional test were retrospectively analyzed. Echocardiography and pulmonary functional parameters before aortic valve replacement were collected. COPD severity was defined according to criteria from the Society of Thoracic Surgeons. COPD was present in 128 patients (32%) with severe AS. Patients without COPD had smaller left ventricular (LV) mass and LV end-systolic volume and better LV function than the group with COPD. During a median follow-up of 32 months, 92 patients (23%) died. The survival rates were significantly lower in patients with moderate and severe COPD (log-rank p = 0.003). In the multivariable Cox regression analysis, any grade of COPD was associated with an approximately 2-fold increased risk of all-cause mortality (hazard ratio 1.933; 95% confidence interval 1.166 to 3.204; p = 0.011 for mild COPD and hazard ratio 2.028; 95% confidence interval 1.154 to 3.564; p = 0.014 for moderate or severe COPD). In addition to other clinical factors, any grade of COPD was associated with 2-fold increased risk of all-cause mortality.

Feature-tracking computed tomography left atrial strain and long-term survival after transcatheter aortic valve implantation.

AIMS: Aortic stenosis (AS) induces left atrial (LA) remodelling through the increase of left ventricular (LV) filling pressures. Peak LA longitudinal strain (PALS), reflecting LA reservoir function, has been proposed as a prognostic marker in patients with AS. Feature-tracking (FT) multi-detector computed tomography (MDCT) allows assessment of LA strain from MDCT data. The aim of this study is to investigate the association between PALS using FT MDCT and survival in patients with severe AS who underwent transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: A total of 376 patients (mean age 80 ± 7 years, 53% male) who underwent MDCT before TAVI and had suitable data for assessment of PALS using dedicated FT software, were included. The patients were classified into four groups according to PALS quartiles; PALS > 19.3% (Q1, highest reservoir function), 15.0-19.3% (Q2), 9.1-14.9% (Q3), and ≤9.0% (Q4, lowest reservoir function). The primary outcome was all-cause mortality. During a median of 45 (22-68) months follow-up, 148 patients (39%) died. On multivariable Cox regression analysis, PALS was independently associated with all-cause mortality [hazard ratio (HR): 1.044, 95% confidence interval (CI): 1.012-1.076, P = 0.006]. Compared with patients in Q1, patients in Q3 and Q4 were associated with higher risk of mortality after TAVI [HR: 2.262 (95% CI: 1.335-3.832), P = 0.002 for Q3, HR: 3.116 (95% CI: 1.864-5.210), P < 0.001 for Q4]. CONCLUSION: PALS assessed with FT MDCT is independently associated with all-cause mortality after TAVI.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.

BACKGROUND: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. METHODS: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. RESULTS: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. CONCLUSIONS: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Prognostic Value of Nonalcoholic Fatty Liver Disease in Patients With Severe Aortic Stenosis Who Underwent Transcatheter Aortic Valve Implantation.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events. Although the association between NAFLD and aortic valve sclerosis has been described, the prevalence and prognostic implications of NAFLD among patients with severe aortic stenosis (AS) have not been described. In addition, the effect of the presence of severe tricuspid regurgitation (TR) on the prevalence of NAFLD remains unexplored. Accordingly, we investigated the prognostic implications of NAFLD among patients with severe AS with and without concomitant significant TR. A total of 538 patients (aged 80 ± 7 y, 49.6% men) who underwent noncontrast computed tomography before transcatheter aortic valve implantation (TAVI) between 2007 and 2019 were included. NAFLD was defined as a liver-to-spleen attenuation ratio <1.0 on noncontrast computed tomography. NAFLD was present in 118 patients (21.9%). There were no significant differences in pulmonary arterial pressure, right atrial pressure, or the prevalence of significant TR between patients with and without NAFLD. During a median follow-up of 47 months (interquartile range 20 to 70 months), 224 patients (41.6%) died. Univariate Cox regression analysis demonstrated that NAFLD was not significantly associated with all-cause death among patients treated with TAVI (hazard ratio 1.32, 95% confidential interval 0.97 to 1.79, p = 0.07). In conclusion, among patients with severe AS who underwent TAVI, the prevalence of significant TR and the clinical outcomes were similar in patients with and without NAFLD.

Incremental value of left ventricular global longitudinal strain in moderate aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Moderate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction. METHODS: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reduced LV ejection fraction (EF) (<50%) were identified. LVGLS was evaluated with speckle-tracking echocardiography. Patients were divided into 2 groups according to an LVGLS value of 11%, based on spline curve analysis. The primary endpoint was all-cause mortality. RESULTS: A total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS <11% (25% and 60%) versus LVGLS ≥11% (10% and 27%) (p < 0.001). On multivariable analysis, LVGLS as a continuous variable (HR 0.753; 95% CI 0.673-0.843; p < 0.001) and as a categorical variable (<11%) (HR 3.028; 95% CI 1.623-5.648; p < 0.001) were independently associated with outcomes, whereas LVEF was not. LVGLS provided additional prognostic information in patients with/without coronary artery disease and with mildly versus severely reduced LVEF. In addition, LVGLS had incremental prognostic value over established risk factors, including LVEF. CONCLUSION: The combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF.

Comparison of the Quantity of Calcium in the Aortic Valve and the Coronary Arteries in Men Versus Women Who Underwent Transcatheter Aortic Valve Implantation.

Several studies have shown an association between aortic stenosis (AS) and coronary atherosclerosis. This study aimed to evaluate the gender differences in aortic valve calcium (AVC) and coronary artery calcium (CAC) and the association between CAC and all-cause mortality in patients with severe AS. A total of 260 patients (80 ± 7 years, 39% men) with severe AS who were scheduled for transcatheter aortic valve implantation (TAVI) were included. AVC and CAC before TAVI were assessed by noncontrast cardiac computed tomography. Patients with coronary intervention or aortic valve replacement before cardiac computed tomography were excluded. Standard reference values of CAC score were used to classify the percentile groups and the distribution of AVC was assessed. The primary end point was all-cause mortality. In men, the AVC score was 3,911 Hounsfield units (HUs) (interquartile range [IQR] 2,525 to 5,259) and in women, 2,409 HU (IQR 1,588 to 3,359) (p <0.001). CAC score in men was 824 HU (IQR 328 to 1,855) and in women, 478 HU (IQR 136 to 962) (p <0.001). In men, the AVC score increased along with the CAC score, whereas in women, the AVC score was similar across the CAC percentile groups. During a median follow-up of 1,095 days, 59 patients (23%) died. No significant gender-difference was seen in all-cause mortality for CAC score (p = 0.187). Men with severe AS show higher AVC and CAC scores than women. Although the pattern of CAC distribution was similar between men and women, the AVC score increased along with the CAC score in men; whereas, in women, the AVC score remained similar across the various percentiles. CAC score was not associated with cumulative mortality in patients with severe AS who underwent TAVI.

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

BACKGROUND: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied. OBJECTIVES: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction. METHODS: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes. RESULTS: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group). CONCLUSIONS: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

BACKGROUND: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown. OBJECTIVES: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS. METHODS: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m2, and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality. RESULTS: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality. CONCLUSIONS: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.

Effects of Left Bundle Branch Block and Pacemaker Implantation on Left Ventricular Systolic Function After Transcatheter Aortic Valve Implantation.

Permanent pacemaker implantation (PPI) and left bundle branch block (LBBB) frequency after transcatheter aortic valve implantation (TAVI) and their effect on left ventricular ejection fraction (LVEF) remain controversial. We evaluated the incidence of PPI and new-onset LBBB after TAVI and their impact on LVEF at 6-month follow-up. Moreover, the impact of right ventricular (RV) pacing burden on changes in LVEF after TAVI was analyzed. The electrocardiograms of 377 patients (age 80 ± 7 years, 52% male) treated with TAVI were collected at baseline, after the procedure, at discharge, and at each outpatient follow-up. LVEF was measured at baseline before TAVI and 6 months after the procedure. Patients were divided into 3 groups according to the occurrence of LBBB, the need for PPI, or the absence of new conduction abnormalities. In patients with PPI, the influence of RV pacing burden on LVEF was analyzed. New-onset LBBB after TAVI occurred in 92 patients (24%), and PPI was required in 55 patients (15%). In patients without new conduction abnormalities, LVEF significantly increased during follow-up (56 ± 14% to 61 ± 12%, p <0.001). Patients with a baseline LVEF ≤50% presented with a significant recovery in LVEF, although the recovery was less pronounced in patients with new-onset LBBB. Moreover, patients with a baseline LVEF ≤50% who received PPI showed an improvement in LVEF at 6 months regardless of the RV pacing burden. New-onset LBBB hampers the recovery of LVEF after TAVI. Among patients with an LVEF ≤50%, pressure overload relief counteracts the effects of new-onset LBBB or RV pacing.

Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis.

OBJECTIVE: To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function. METHODS: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR). RESULTS: Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020). CONCLUSIONS: LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention.

Prognostic Implications of Change in Left Ventricular Ejection Fraction After Transcatheter Aortic Valve Implantation.

Reduced left ventricular (LV) systolic function is associated with worse prognosis in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). We aimed to examine the changes in left ventricular ejection fraction (LVEF) after TAVI among patients with varying baseline LVEF. Moreover, variables associated with lack of LVEF improvement were identified and the association with long-term outcomes was investigated. A total of 560 patients (age 80 ± 7 years, 53% men) with severe AS who underwent transfemoral TAVI between 2007 and 2019 were selected. LVEF was assessed from transthoracic echocardiography at baseline (before TAVI) and at 6 and 12 months after TAVI. Patients were stratified according to baseline LVEF: (1) LVEF ≥50%, (2) LVEF 40% to 49%, and (3) LVEF <40%. The clinical end point was ≥5% LVEF improvement. The primary outcome was all-cause mortality. Patients with baseline LVEF<40% showed greater increase in LVEF than those with baseline LVEF 40% to 49% and LVEF ≥50% (from 33% ± 6% to 43% ± 10%, p <0.001; from 45% ± 3% to 52% ± 8%, p <0.001; and from 58% ± 5% to 59% ± 7%, p = 0.012, respectively, p for interaction <0.001). Coronary artery disease (odds ratio [OR] 1.80 [95% confidence interval (CI) 1.06 to 3.06], p = 0.031), myocardial infarction (OR 2.07 [95% CI 1.19 to 3.61], p = 0.010), and permanent pacemaker (OR: 1.93 [95% CI 1.25 to 3.00], p = 0.003) were independently associated with the lack of ≥5% LVEF improvement. During a median follow-up of 3.8 (interquartile range 2.6 to 5.2) years, 176 patients died (31%). Patients with ≥5% LVEF improvement had similar outcomes compared with those with <5% LVEF improvement (log-rank p = 0.89). In conclusion, patients with severe AS and baseline LVEF <40% had the greatest improvement in LVEF at 1-year follow-up after TAVI. Coronary artery disease, myocardial infarction, and permanent pacemaker were associated with lack of LVEF improvement. However, LVEF improvement at 12 months was not associated with long-term outcomes.

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis.

Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS. METHODS: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality. RESULTS: A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality. CONCLUSIONS: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved.

Left ventricular remodelling patterns in patients with moderate aortic stenosis.

AIMS: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS. METHODS AND RESULTS: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 ± 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P < 0.001). After multivariable adjustment, CH remained independently associated with mortality (HR 1.258, 95% CI 1.016-1.558; P = 0.035), whereas both CH (HR 1.291, 95% CI 1.088-1.532; P = 0.003) and EH (HR 1.217, 95% CI 1.008-1.470; P = 0.042) were associated with the composite endpoint of death or AVR. CONCLUSION: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention.

Multimodality Imaging to Explore Sex Differences in Aortic Stenosis.

The aim of this article is to review sex differences in aortic stenosis (AS) assessed with multimodality imaging. Echocardiography remains the mainstay imaging technique to diagnose AS and provides important insights into the differences between men and women in relation to valve haemodynamic and left-ventricular response. However, echocardiography does not have adequate resolution to provide important insights into sex differences in the degenerative, calcific pathophysiological process of the aortic valve. CT shows that women with AS have more fibrotic changes of the aortic valve whereas men show more calcific deposits. Cardiac magnetic resonance shows that women have left ventricles that are less hypertrophic and smaller compared with those of men, while men have more replacement myocardial fibrosis. These differences may lead to different responses to aortic valve replacement because myocardial diffuse fibrosis but not replacement myocardial fibrosis may regress after the procedure. Sex differences in the pathophysiological process of AS can be assessed using multimodality imaging, assisting in decisionmaking in these patients.

Moderate aortic stenosis: importance of symptoms and left ventricular ejection fraction.

AIMS: The aim of this study is to investigate the independent determinants of survival in patients with moderate aortic stenosis (AS), stratified by severity of symptoms and left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified. Patients were stratified by New York Heart Association (NYHA) functional class (NYHA I, NYHA II, or NYHA III-IV) and LVEF (LVEF ≥60%, LVEF 50-59%, or LVEF <50%) at the time of moderate AS diagnosis. The primary endpoint was all-cause mortality, while the secondary endpoint included all-cause mortality and aortic valve replacement. Of 1961 patients with moderate AS (mean age 73 ± 10 years, 51% men), 1108 (57%) patients were in NYHA class I, while 527 (27%) and 326 (17%) patients had symptoms of NYHA class II and III-IV, respectively. Regarding LVEF, 1032 (53%) had LVEF ≥60%, 544 (28%) LVEF 50-59%, and 385 (20%) LVEF <50%. During a median follow-up of 50 (23-82) months, 868 (44%) patients died. On multivariable analysis, NYHA class II [hazard ratio (HR): 1.633; 95% confidence interval (CI): 1.431-1.864; P < 0.001], NYHA class III-IV (HR: 2.084; 95% CI: 1.797-2.417; P < 0.001), LVEF 50-59% (HR: 1.194; 95% CI: 1.013-1.406; P = 0.034), and LVEF <50% (HR: 1.694; 95% CI: 1.417-2.026; P < 0.001) were independently associated with increased mortality. CONCLUSION: Moderate AS is associated with poor long-term survival. Baseline symptom severity and LVEF are associated with worse outcomes in these patients. Patients with low-normal LVEF (<60%) and mild symptoms (NYHA II) already have an increased risk of adverse events.

Left ventricular remodelling in bicuspid aortic valve disease.

AIMS: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction. METHODS AND RESULTS: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD. CONCLUSIONS: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Bicuspid Aortic Valve Stenosis.

Background: Sex-specific thresholds of computed tomography (CT)-derived aortic valve calcification (AVC) or AVC density (AVCd) to identify severe aortic stenosis (AS) have been established in populations that consisted mainly of Caucasians with a tricuspid aortic valve. The objective of this study was to evaluate the accuracy (i.e., sensitivity and specificity) of previously established thresholds to identify severe AS in patients with bicuspid aortic valve (BAV) and according to ethnicity: Caucasian vs. Asian. Methods: We built a multicenter registry of echocardiographic and CT data collected in BAV patients with at least mild AS and preserved left ventricular ejection fraction from 7 different centers. Anatomic severity of AS obtained by CT-derived AVC and AVCd was compared to hemodynamic severity of AS obtained by echocardiography. Results: Among 485 BAV patients (60% men, 73% Asians), the best thresholds of AVC and AVCd to identify severe AS in BAV patients were 2315 arbitrary units (AU) (sensitivity [Se]/specificity [Spe] = 82/78%) in men, 1103 AU (Se/Spe = 80/82%) in women, and 561 AU/cm2 (Se/Spe = 86/91%) in men, and 301 AU/cm2 (Se/Spe = 83/82%) in women, respectively. According to ethnicity, thresholds for severe AS in Caucasian patients were, respectively, in men and women: 2208 AU (Se/Spe = 83/83%) and 1230 AU (Se/Spe = 87/82%) for AVC and 474 AU/cm2 (Se/Spe = 88/83%) and 358 AU/cm2 (Se/Spe = 80/82%) for AVCd. In Asian patients, they were 2582 AU (Se/Spe = 76/78%) and 924 AU (Se/Spe = 84/80%) for AVC and 640 AU/cm2 (Se/Spe = 82/89%) and 255 AU/cm2 (Se/Spe = 86/80%) for AVCd. Conclusions: The optimal thresholds to identify hemodynamically severe AS in BAV patients are similar in Caucasians but appear to be higher in Asian men, compared with thresholds previously reported in tricuspid aortic valve patients. Nonetheless, the thresholds currently proposed in the guidelines have good accuracy and can be applied in BAV patients to confirm AS severity.