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.

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.

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.

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.

Sex-Related Differences in Medically Treated Moderate Aortic Stenosis.

Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS. Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement. Results: A total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes. Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed.

Discordant severity criteria in patients with moderate aortic stenosis: prognostic implications.

BACKGROUND: The criteria to define the grade of aortic stenosis (AS)-aortic valve area (AVA) and mean gradient (MG) or peak jet velocity-do not always coincide into one grade. Although in severe AS, this discrepancy is well characterised, in moderate AS, the phenomenon of discordant grading has not been investigated and its prognostic implications are unknown. OBJECTIVES: To investigate the occurrence of discordant grading in patients with moderate AS (defined by an AVA between 1.0 cm² and 1.5 cm² but with an MG <20 mm Hg) and how these patients compare with those with concordant grading moderate AS (AVA between 1.0 cm² and 1.5 cm² and MG ≥20 mm Hg) in terms of clinical outcomes. METHODS: From an ongoing registry of patients with AS, patients with moderate AS based on AVA were selected and classified into discordant or concordant grading (MG <20 mm Hg or ≥20 mm Hg, respectively). The clinical endpoint was all-cause mortality. RESULTS: Of 790 patients with moderate AS, 150 (19.0%) had discordant grading, moderate AS. Patients with discordant grading were older, had higher prevalence of previous myocardial infarction and left ventricular (LV) hypertrophy, larger LV end-diastolic and end-systolic volume index, higher LV filling pressure and lower LV ejection fraction and stroke volume index as compared with their counterparts. After a median follow-up of 4.9 years (IQR 3.0-8.2), patients with discordant grading had lower aortic valve replacement rates (26.7% vs 44.1%, p<0.001) and higher mortality rates (60.0% vs 43.1%, p<0.001) as compared with patients with concordant grading. Discordant grading moderate AS, combined with low LV ejection fraction, presented the higher risk of mortality (HR 2.78 (2.00-3.87), p<0.001). CONCLUSION: Discordant-grading moderate AS is not uncommon and, when combined with low LV ejection fraction, is associated with high risk of mortality.

Incremental value of left ventricular global longitudinal strain in a newly proposed staging classification based on cardiac damage in patients with severe aortic stenosis.

AIMS: Cardiac damage in severe aortic stenosis (AS) can be classified according to a recently proposed staging classification. The present study investigated the incremental prognostic value of left ventricular (LV) global longitudinal strain (GLS) over stages of cardiac damage in patients with severe AS. METHODS AND RESULTS: From an ongoing registry, a total of 616 severe symptomatic AS patients with available LV GLS by speckle tracking echocardiography were selected and retrospectively analysed. Patients were categorized according to cardiac damage on echocardiography: Stage 0 (no damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage), or Stage 4 (right ventricular damage). LV GLS was divided by quintiles and assigned to the different stages. The endpoint was all-cause mortality. Over a median follow-up of 44 [24-89] months, 234 (38%) patients died. LV GLS was associated with all-cause mortality independent of stage of cardiac damage. After incorporation of LV GLS by quintiles into the staging classification, Stages 2-4 were independently associated with outcome. LV GLS showed incremental prognostic value over clinical characteristics and stages of cardiac damage. CONCLUSION: In this large single-centre cohort of severe AS patients, incorporation of LV GLS by quintiles in a novel proposed staging classification resulted in refinement of risk stratification by identifying patients with more advanced cardiac damage. LV GLS was shown to provide incremental prognostic value over the originally proposed staging classification.

Staging Cardiac Damage in Patients With Symptomatic Aortic Valve Stenosis.

BACKGROUND: In severe aortic stenosis (AS), patients often show extra-aortic valvular injury. Recently, a new staging system for severe AS has been proposed on the basis of the extent of cardiac damage. OBJECTIVES: The present study evaluated the prevalence and prognostic impact of these different stages of cardiac damage in a large, real-world, multicenter cohort of symptomatic severe AS patients. METHODS: From the ongoing registries from 2 academic institutions, a total of 1,189 symptomatic severe AS patients were selected and retrospectively analyzed. According to the extent of cardiac damage on echocardiography, patients were classified as Stage 0 (no cardiac damage), Stage 1 (left ventricular damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage), or Stage 4 (right ventricular damage). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, and cardiac-related hospitalization). RESULTS: On the basis of the proposed classification, 8% of patients were classified as Stage 0, 24% as Stage 1, 49% as Stage 2, 7% as Stage 3, and 12% as Stage 4. On multivariable analysis, cardiac damage was independently associated with all-cause mortality and combined outcome, although this was mainly determined by Stages 3 and 4. CONCLUSIONS: In this large multicenter cohort of symptomatic severe AS patients, stage of cardiac injury as classified by a novel staging system was independently associated with all-cause mortality and combined endpoint, although this seemed to be predominantly driven by tricuspid valve or pulmonary artery vasculature damage (Stage 3) and right ventricular dysfunction (Stage 4).