Moderate Aortic Stenosis Patients Research Articles

Abstract 15422: Diffuse Myocardial Fibrosis Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Introduction: Patients with moderate or asymptomatic severe aortic stenosis (AS) are at increased risk of cardiovascular events, but markers to guide intervention are lacking. We investigated the use of cardiovascular magnetic resonance (CMR) to identify drivers of outcome. Methods: Moderate (aortic valve area [AVA] 1.0-1.5 cm2) or asymptomatic severe AS patients (AVA≤1.0 cm2 and NYHA functional class I-II) (n=457) were prospectively enrolled from five international sites and parameters including extracellular volume fraction (ECV%) and late gadolinium enhancement were analyzed on CMR. Clinical events were defined as all-cause mortality and admission for heart failure. Results: Moderate AS patients had smaller left ventricular (LV) mass and less diastolic dysfunction compared to asymptomatic severe AS patients, but showed no difference in the extent of myocardial fibrosis and scar. During median 5.7-years follow-up, 83 clinical events occurred. Patients with clinical events had smaller AVA, greater diastolic dysfunction, and higher ECV% (median [interquartile range] ECV% 26.3% [24.3-29.8] vs 28.2% [25.5-30.8], P=0.003). There was a stepwise increase of clinical events across ECV tertiles. ECV% was associated with clinical outcome (adjusted HR 1.05, 95% CI 1.00–1.09, P=0.035), independent of AVA and aortic valve replacement as a time-dependent covariate. The prognostic significance of ECV% was consistent when AS severity was alternatively defined using aortic peak velocity and mean pressure gradient, and also across subgroups by AS severity and symptoms, AVA, aortic peak velocity, mean pressure gradient, and left ventricular ejection fraction (Figure). Conclusions: Increased diffuse myocardial fibrosis is associated with poor outcomes in moderate and asymptomatic severe AS patients and can help identify those who require closer surveillance and possibly earlier intervention.

Physician assessment of aortic stenosis severity, quantitative parameters, and long-term outcomes: Results from the KP-VALVE project

BackgroundContemporary outcomes for aortic stenosis (AS) and the association between physician-assessed AS severity and quantitative parameters is poorly understood. We aimed to evaluate AS natural history, compare outcomes for physicians’ AS assessment vs. quantitative parameters, and identify AS parameters with the most explanatory power. MethodsWe ascertained physician-assessed AS severity, echocardiographic parameters, and clinical data for 546,769 patients from 2008-2018, examined multivariable associations of physician-assessed AS severity and number of quantitative severe AS parameters with death, cardiovascular hospitalization, and aortic valve replacement, and estimated the relative contribution of different quantitative AS parameters on outcomes. ResultsAmong 49,604 AS patients (mean [SD] age 77 [11] years), 17.6% had moderate, 3.6% moderate-severe, and 9.4% severe AS. During median 3.7 [IQR 1.7-6.8] years, physician-assessed AS severity strongly correlated with outcomes, with moderate AS patients tracking closest to mild AS, and moderate-to-severe AS patients more comparable to severe AS. Although the number of quantitative severe AS parameters strongly predicted outcomes (adjusted HR [95% CI] for death 1.40 [1.34-1.46], 1.70 [1.56-1.85], and 1.78 [1.63-1.94] for 1, 2, and 3 parameters, respectively), aortic valve area <1.0 cm2 was the most frequent severe AS parameter, explained the largest relative contribution (67%), and was common in patients classified as moderate (21%) or moderate-severe (56%) AS. ConclusionsPhysician-assessed AS severity predicts outcomes, with cumulative effects for each severe AS parameter. Moderate AS includes a wide spectrum of patients, with discordant AVA <1.0 cm2 being both common and predictive. Better identification of non-classical severe AS phenotypes may improve outcomes.

Impact of low-density lipoprotein cholesterol on progression of aortic valve sclerosis and stenosis.

Little research has been assessed atherosclerotic risk factors at various stages of calcific aortic valve disease. This study sought to determine risk factors of patients with aortic valve sclerosis (AVS) and mild to moderate aortic stenosis (AS). The study included 1,007 patients diagnosed with AVS or mild to moderate AS according to echocardiographic criteria. Patients were identified as a rapid progression group if the annualized difference in peak aortic jet velocity (Vmax) between two echocardiographic examinations was >0.08 m/s/yr in AVS and >0.3 m/s/yr in AS, respectively. We used multivariable logistic regression analyses to assess the factors associated with rapid disease progression or progression to severe AS. Among 526 AVS patients, higher LDL-C level (odds ratio [OR] 1.22/per 25 mg/dl higher LDL-C, 95% confidence interval [CI] 1.05-1.43) was significantly associated with rapid disease progression. Compared to patients with LDL-C level <70 mg/dl, the adjusted OR for rapid progression were 1.32, 2.15, and 2.98 for those with LDL-C level of 70-95 mg/dl, 95-120 mg/dl, and ≥120 mg/dl, respectively. Among 481 mild to moderate AS patients, the baseline Vmax (OR 1.79/per 0.5 m/s higher Vmax, 95% CI 1.18-2.70) was associated with rapid progression. Compared to patients with Vmax 2.0-2.5 m/s, the adjusted OR for rapid progression were 2.47, 2.78, and 3.49 for those with Vmax of 2.5-3.0 m/s, 3.0-3.5 m/s, and 3.5-4.0 m/s, respectively. LDL-C and baseline Vmax values were independently associated with progression to severe AS. Atherosclerotic risk factors such as LDL-C were significantly associated with the rapid progression in AVS and baseline Vmax was important in the stage of mild to moderate AS.

Trans-Aortic Flow Turbulence and Aortic Valve Inflammation: A Pilot Study Using Blood Speckle Imaging and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Patients With Moderate Aortic Stenosis.

18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT) has been proven to be useful in identification of microcalcifications, which are stimulated by inflammation. Blood speckle imaging (BSI) is a new imaging technology used for tracking the flow of blood cells using transesophageal echocardiography (TEE). We evaluated the relationship between turbulent flow identified by BSI and inflammatory activity of the aortic valve (AV) as indicated by the 18F-NaF uptake index in moderate aortic stenosis (AS) patients. This study enrolled 18 moderate AS patients diagnosed within the past 6 months. BSI within the aortic root was acquired using long-axis view TEE. The duration of laminar flow and the turbulent flow area ratio were calculated by BSI to demonstrate the degree of turbulence. The maximum and mean standardized uptake values (SUVmax, SUVmean) and the total microcalcification burden (TMB) as measured by 18F-NaF PET/CT were used to demonstrate the degree of inflammatory activity in the AV region. The mean SUVmean, SUVmax, and TMB were 1.90 ± 0.79, 2.60 ± 0.98, and 4.20 ± 2.18 mL, respectively. The mean laminar flow period and the turbulent area ratio were 116.1 ± 61.5 msec and 0.48 ± 0.32. The correlation between SUVmax and turbulent flow area ratio showed the most positive and statistically significant correlation, with a Pearson's correlation coefficient (R²) of 0.658 and a p-value of 0.014. The high degree of trans-aortic turbulence measured by BSI was correlated with severe AV inflammation.

Abstract 10747: Left Atrial Volume Index is Associated With New-Onset Heart Failure Admission and Cardiovascular Death in Patients With Asymptomatic Moderate Aortic Stenosis

Background: Left atrium enlargement is the marker of increased left ventricular (LV) filling pressure and morphological indicator of chronically increased hemodynamic burden. However, the potential utility and clinical significance of left atrial volume (LAV) index in asymptomatic moderate aortic stenosis (AS) patients have been unknown. Therefore, we assessed the impact of LAV index on cardiovascular events in asymptomatic moderate AS patients. Methods: We retrospectively analyzed 549 patients (mean age 79±13 years) with asymptomatic moderate AS (mean transaortic pressure gradient 20 to 39 mmHg) and LVEF ≥50 %. Cardiovascular events were defined as cardiovascular death or admission for heart failure (HF). Results: During a follow-up period (median, 1301 days; range, 296 to 2179 days), 216 patients underwent aortic valve replacement (AVR) or balloon aortic valvuloplasty (BAV), and 132 HF admission and 37 cardiovascular deaths occurred. In the multivariable analysis, LAV index, lateral E/e′, and peak tricuspid regurgitation velocity were independent predictors of cardiovascular events (Hazard ratio (HR) 1.07 [1.05 to 1.09]; HR 1.04 [1.00 to 1,08]; HR 1.04 [1.00 to 1.07], respectively) after adjusting for age, female, body mass index, previous myocardial infarction, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, moderate mitral regurgitation, E velocity, LV hypertrophy, and surgical or transcatheter AVR or BAV. LAV index of 27 mL/m 2 was the optimal cutoff value for predicting cardiovascular events with sensitivity of 89% and specificity of 60% and C-statistics for LAV index demonstrated superiority to lateral E/e′ and peak tricuspid regurgitation velocity ( P &lt;0.001) (Figure). Conclusion: LAV index is an important predictor for cardiovascular events in asymptomatic moderate AS patients.

Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis.

The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined. This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease. Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement. Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95%CI: 6.9 to 11.7) for all-cause death, 4.9 (95%CI: 3.1 to 7.5) for cardiac death, 3.9 (95%CI: 1.9 to 8.2) for heart failure, 1.1 (95%CI: 0.8 to 1.5) for sudden death, and 7.2 (95%CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P< 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95%CI: 5.2 to 52.3) and 4.2 (95%CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95%CI: -6.7 to -1.1) for no or mild AS and+2.2 (95%CI:+0.8 to +3.5) for severe AS patients. Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation.

Profile of Patients With Symptomatic and Asymptomatic Aortic Stenosis in an Australian Clinical Cohort: A Retrospective Outcome Study

Current guidelines recommend aortic valve replacement (AVR) in patients with severe symptomatic aortic stenosis (AS). However, recent data suggest similar benefits of AVR in asymptomatic severe AS, with untreated severe and moderate AS patients having similar mortality profiles. We sought to determine the prevalence of symptoms in a large Australian cohort presenting with moderate and severe AS.

Abstract 11037: Procedural Success, Valve Hemodynamics and Outcomes in Patients with Moderate Aortic Stenosis Undergoing Supra-Annular Transcatheter Aortic Valve Replacement

Introduction: Limited evidence supports the hypothesis that early treatment of symptomatic moderate aortic stenosis (AS) may be beneficial. We seek to study procedural success, valve hemodynamics and clinical outcomes in moderate AS patients who underwent transcatheter aortic valve replacement (TAVR) using a supra-annular self-expanding bioprosthesis. Methods: All patients in the STS/ACC/TVT Registry™ with Evolut R, PRO and PRO+ attempted procedures for indication of primary symptomatic (NYHA class II-IV) moderate AS were included. Moderate AS was defined as mean gradient ≥20 and &lt;40 mm Hg, valve area &gt;1.0 and &lt;1.5 cm 2 , and Vmax &gt;3 and &lt;4 m/s. 2.9% of patients had concurrent severe aortic regurgitation at baseline. Valve-in-valve procedures were excluded. Site reported 30-day event rates are reported using Kaplan-Meier analysis. As a quality-of-life metric, KCCQ scores at 30 days and 1 year are compared to baseline scores using paired t-tests. Results: A total of 811 patients (62.1% men, 77.7 ± 8.7 years of age, STS-PROM score 5.3 ± 3.6, baseline LVEF 56.7 ± 13.3 %) were analyzed. The majority of patients underwent elective procedure (n=762, 94.0%) under conscious sedation (n=439, 54.3%) via iliofemoral approach (n=775, 95.6%). Successful device implantation, defined as correct valve positioning, was achieved in 99.3% of patients with low rates of intraprocedural complications (0.4%). Clinical events at 30 days were: all-cause mortality 1.4%, neurological events 2.5%, major bleeding 4.7% and conduction disturbance requiring pacer/ICD 16.1%. Valve hemodynamics improved post procedure compared to baseline (mean gradient 29.8 ± 4.9 to 8.4 ± 4.9 mm Hg, Vmax 3.5 ± 0.2 to 1.9 ± 0.5 m/s), with mean gradient sustained at 1 year (8.6 ± 4.4 mm Hg). Moderate/severe paravalvular regurgitation was present at similar levels at post procedure and 1 year (1.6% and 3.0%). A significant improvement in quality of life was noted from baseline KCCQ score to 30 days (Δ27.5 ± 25.5, 95% CI 25.4 - 29.5, p&lt;0.001) and 1 year (Δ29.1 ± 26.1, 95% CI 26.2 - 32.1, p&lt;0.001). Conclusions: Patients undergoing TAVR with a self-expanding bioprosthesis for symptomatic moderate AS have high procedural success with sustained improvements in valve hemodynamics and quality of life at 30 days and 1 year.

Abstract 11170: In an Aortic System of Care Model, Adherence to Guideline Based Care is Hampered by Gaps in the Collection, Reporting, and Communication of Echocardiogram Data

Introduction: Aortic Stenosis (AS) is one of the most common and serious valve diseases, affecting 5% of Americans age 65 or older. Currently, there lacks a national system of care addressing the AS care continuum. The American Heart Association (AHA) has a history of success in systems of care and seeks to apply this experience to create similar for the AS patient through the program, Target: AS. Hypothesis: A key step in an Aortic Stenosis system of care is the identification of the patient’s diagnosis echocardiogram (echo). In some cases, the echo is initially performed at a location other than the tertiary hospital, and a consistent method of reporting the results to valve center does not currently exist. This inconsistency impacts guideline-based care. Methods: Target: AS pilot measures, following current guidelines, were developed with guidance from the AHA’s aortic stenosis scientific advisory group. Hospitals entered 2020 baseline data into the Target: AS data collection tool. Data elements were collected towards the measure: “Percentage of moderate aortic stenosis patients receiving a follow-up echocardiogram during the measurement period that is within 24 months of prior echocardiogram.” Sites reviewed data 24 months prior to the baseline year for the initial echo data. Results: 123 patients in 8 pilot hospitals met inclusion criteria. Overall performance - 53% of patients had a follow-up echo with 24 months. Range was 0% - 65%. All but one patient that failed the measure was due to missing or unavailable prior echo. Engagement with sites through 1:1 interviews, data abstractor calls, and quarterly learning collaboratives revealed that hospitals are not able to find initial echo data in medical records, or that the information is not provided in a discrete manner. Conclusions: The 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease states that patients diagnosed with moderate aortic stenosis should have a follow-up echo within 24 months of the diagnostic echo. Early data demonstrates that in all but one case, when hospitals cannot meet this guideline, it is due to not having the initial echo results. A hospital cannot monitor its adherence with guideline-based care when it does not have access to necessary data.

Enhanced Detection of Heart Valve Disease Using Integrated Artificial Intelligence at Scale

BackgroundUndertreatment of heart valve disease creates unnecessary patient risk. Poorly integrated healthcare data systems are unequipped to solve this problem. A software program using a rules-based algorithm to search the electronic health record for heart valve disease among patients treated by healthcare systems in the United States may provide a solution. MethodsA software interface allowed concurrent access to picture archiving communication systems, the electronic health record, and other sources. The software platform was created to programmatically run a rules engine to search structured and unstructured data for identification of moderate or severe heart valve disease using guideline-reported values. Incidence and progression of disease as well as compliance with a care pathway were assessed. ResultsIn 2 health institutions in the United States 60,145 patients had 77,215 echocardiograms. Moderate or severe aortic stenosis (AS) was identified at a rate of 9.1% of patients (5474 and 6910 echocardiograms) in this population. The precision and accuracy of the algorithm for the detection of moderate or severe AS was 92.9% and 98.6%, respectively. Thirty-five percent of patients (441/1265) with moderate stenosis and a subsequent echocardiogram progressed to severe stenosis (mean interval, 358 days). In 1 sample 70.3% of moderate AS patients lacked a 6-month echocardiogram or appointment. The platform enabled 100% accountability for all patients with severe AS. ConclusionsA rules-based software program enhances detection of heart valve disease and can be used to measures disease progression and care pathway compliance.

Influence of left ventricular systolic dysfunction on occurrence of pulsus tardus in patients with aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Background The time between left ventricular (LV) and aortic systolic pressure peaks (TLV-Ao) which could reflect pulsus tardus (PT) is reported to be a marker of severity and be associated with poor prognosis in patients with aortic stenosis (AS). Despite its worldwide recognition, physiological mechanism of PT has not been well elucidated. We hypothesized that not only severity of the AS but also LV systolic dysfunction could be associated with occurrence of PT. Methods TLV-Ao and mean trans-aortic valvular pressure gradient (mean PG) were measured by simultaneous pressure tracing of left ventricle and basal aorta in 74 AS patients with at least moderate severity (78 ± 8 years old). Effective orifice area index (EOAI) was estimated by using continuity equation from transthoracic echocardiography and severe AS was defined as EOAI ± 0.60 cm²/m². Global longitudinal strain (GLS) was measured by using speckle-tracking method and expressed as an absolute value. Results TLV-Ao, mean PG, and EOAI was 87 ± 30 msec, 51 ± 21 mmHg, and 0.51 ± 0.14 cm² respectively. A weak correlation was observed between EOAI and TLV-Ao (Figure). In 9 out of 17 moderate AS patients (A in Figure), TLV-Ao was prolonged over the previously reported cut-off value (≥66 msec), on the other hand, it was not prolonged in 11 out of 57 severe AS patients (D in Figure). When the patients were divided by TLV-Ao of 66 msec, mean PG was not different between patients with prolonged TLV-Ao and those without in moderate AS patients (Figure, A vs B; NS), whereas GLS was significantly reduced in prolonged TLV-Ao group (P = 0.0383). In patients with severe AS, mean PG was significantly higher (P &amp;lt; 0.0001) in patients with prolonged TLV-Ao than in those without (Figure, C vs D), whereas GLS was comparable between the groups. In overall patients, multivariable analysis revealed that not only mean PG (β=0.54) but also GLS (β=-0.23) was an independent determinant of TLV-Ao. Conclusion The occurrence of pulsus tardus could be associated not only with severity of the AS but also with LV systolic dysfunction in patients with AS. Abstract Figure

Survival of patients with moderate aortic stenosis: propensity score matching analysis

Abstract Introduction and purpose Data on the survival of patients with moderate aortic stenosis (AS) is conflicting. The purpose of the current analysis was to assess survival of moderate AS patients. Methods SHARE is an historical retrospective cohort of all cardiovascular patients evaluated in an Israeli tertiary hospital between 2007 and 2019. The current analysis included all patients who underwent echocardiographic evaluation. Aortic stenosis severity was extracted for all patients from the echocardiographic reports. All-cause mortality and was available for all patients. Subjects with severe AS or aortic valve replacement were excluded from the analysis. Results Cohort included 97,561 subjects of whom 42,187 (43.2%) were outpatients. Final cohort included 93,889 patients with a mean age of 66±17 (58% men). There were 2,949 (3%) with moderate AS. During a median follow up of 52 [IQR 22–89] months 17,173 (18%) patients died. Kaplan-Meier survival analysis demonstrated worse cumulative probability of death of 51%±2% vs. 20%±0% at 5 years for patients with moderate AS vs. mild or no AS, respectively (p Log rank &amp;lt;0.001). Sub-analysis of 32,745 patients for whom clinical laboratory and medication data was available yielded consistent results in a comprehensive multivariate model such that patients with moderate AS (N=1,381) were 26% more likely to die (95% CI: 1.17–1.37, p&amp;lt;0.0001). Finally, a propensity score matching of patients with moderate AS and controls with no or mild AS (N=1,381) successfully demonstrated that patients with moderate AS were 40% more likely to die during follow up (95% CI 1.25–1.57, p&amp;lt;0.001; FIGURE). Four-years mortality rates were 2 fold higher for patients with moderate AS compared with controls (OR = 1.96, 95% CI 1.6–2.4, p&amp;lt;0.001). Interaction analysis demonstrated that the association of moderate AS with survival was not dependent on left ventricular ejection fraction. Conclusion Moderate AS is associated with worse survival. Our findings underscore the importance of careful clinical observation as well as the need for further studies. Figure 1 Funding Acknowledgement Type of funding source: None

Left Ventricular Global Longitudinal Strain Is Associated With Long-Term Outcomes in Moderate Aortic Stenosis.

Left ventricular global longitudinal strain (GLS) is associated with long-term outcomes of patients with severe aortic stenosis. However, its prognostic value in patients with moderate aortic stenosis remains unknown. Patients diagnosed with moderate aortic stenosis (1.0< aortic valve area ≤1.5 cm2) and left ventricular ejection fraction ≥50% were identified. GLS was assessed by 2-dimensional strain imaging using speckle-tracking method. All-cause mortality was assessed according to the median GLS value. Two hundred eighty-seven patients were included (median age 76 years; 47% male). Mean aortic valve area was 1.25 cm2, left ventricular ejection fraction 62%, and median GLS -15.2%. During a median follow-up of 3.9 years, there were 103 deaths (36%). Mortality was higher in patients with GLS>-15.2% (hazard ratio 2.62 [95% CI 1.69-4.06]) compared with patients with GLS ≤-15.2% even after adjusting for confounders. Mortality rates at 1, 3, 5 years were 21%, 35%, 48%, respectively, in patients with GLS >-15.2%, and 6%, 15%, 19% in those with GLS ≤-15.2%. Even among those with left ventricular ejection fraction ≥60%, GLS discriminated higher-risk patients (P=0.0003). During follow-up, 106 (37%) patients underwent aortic valve replacement with median waiting-time of 2.4 years, and their survival was better than patients without aortic valve replacement. Among those patients undergoing aortic valve replacement, prognosis was still worse in patients with GLS >-15.2% (P=0.04). Mortality rates at 1, 3, 5 years were 2%, 10%, 20%, respectively, in patients with GLS >-15.2% and 2%, 5%, 6% in those with GLS ≤-15.2%. Impaired GLS in moderate aortic stenosis patients is associated with higher mortality rates even among those undergoing aortic valve replacement.

Cardiac Magnetic Resonance Feature Tracking in Aortic Stenosis: Exploration of Strain Parameters and Prognostic Value in Asymptomatic Patients with Preserved Ejection Fraction

ObjectiveTo determine the most valuable cardiac magnetic resonance feature tracking (CMR-FT) parameters for evaluating aortic stenosis (AS) and determine whether they can predict the prognosis in asymptomatic AS patients with preserved ejection fraction (pEF).Materials and MethodsA prospective cohort of 123 moderate to severe AS patients (60 males, 68.6 ± 9.2 years) and 32 control subjects (14 males, 67.9 ± 4.4 years) underwent echocardiography and 3T CMR imaging from 2011–2015. CMR cine images were analyzed using CMR-FT to assess the left ventricular radial, circumferential, and longitudinal peak strain (PS) in 2- and 3-dimensions. The primary endpoints were clinical cardiac events (CCEs), including cardiac death, heart failure, and AS-associated symptom development. For statistical analysis, logistic regression and log-rank tests were used.ResultsGlobal PSs differed between AS patients and controls and between severe and moderate AS patients (p < 0.05). Two-dimensional (2D) global radial and longitudinal PSs changed gradually with the severity of AS groups (p < 0.001). Twenty-two of 67 asymptomatic AS patients with pEF experienced CCEs during the follow-up (median: 31.1 months). 2D global longitudinal PS (GLPS) was the single risk factor for CCE (p = 0.017). The relative risk for CCE was 3.9 (p = 0.016, 95% confidence interval: 1.2–11.9) based on 2D GLPS with a cutoff of −17.9% according to receiver operating characteristic curve analysis. Survival analysis demonstrated that asymptomatic AS patients with pEF having impaired 2D GLPS experienced worse event-free survival than the others (p = 0.041).Conclusion2D global longitudinal and radial PSs may reflect cardiac dysfunction according to the degree of AS. 2D GLPS might be a prognostic predictor of CCEs in asymptomatic AS patients with pEF.

P5582Predicting the clinical outcomes in moderate aortic stenosis: implementation of the newly proposed staging classification

Abstract Background While symptomatic severe aortic stenosis (AS) carries a worse prognosis and early intervention is favoured, it is always assumed that patients with moderate AS are more stable and their disease progression can be monitored yearly. However, it is known that patients with moderate AS have a higher risk of cardiovascular events but is unclear if other factors may also affect the overall prognosis. Purpose In this multicentre registry of patients with moderate AS, the prognostic value of a new staging classification on the extent of cardiac damage was examined. Methods Based on the echocardiographic findings at the time of diagnosis of moderate AS (valve area &gt;1.0 and ≤1.5 cm2), they were re-classified into five stages depending on the extra-aortic valvular cardiac damage: no signs of cardiac damage (Stage 0), left ventricular (LV) damage [LV ejection fraction &lt;50%, LV mass index &gt;95 g/m2 for women or &gt;115 g/m2 for men or E/e' &gt;14] (Stage 1), mitral valve or left atrial (LA) damage [LA volume index &gt;34 ml/m2 or mitral regurgitation ≥grade 3 or presence of atrial fibrillation] (Stage 2), tricuspid valve or pulmonary artery vasculature damage [systolic pulmonary arterial pressure ≥60 mmHg or tricuspid regurgitation ≥grade 3] (Stage 3), or right ventricular damage [tricuspid annular plane systolic excursion &lt;17 mm] (Stage 4). The clinical endpoint was all-cause mortality. The association between the extent of cardiac damage and all-cause mortality was assessed by the Kaplan Meier method using log-rank test. Results Of the included 522 patients with moderate AS (age 71±11 years, 54% males), 12% (63) of patients were re-classified as Stage 0, 30% (157) in Stage 1, 47% (245) in Stage 2, 6% (31) in Stage 3 and 5% (26) in Stage 4. During follow-up, 43% (226) of patients underwent surgical or transcatheter aortic valve replacement. Over a median follow-up of 6.2 [interquartile range 3.2–9.0] years, 254 (49%) patients died. The cumulative event rates for all-cause mortality increased with increasing stage, particularly for Stages ≥2: 39% for Stage 0, 55% for Stage 1, 67% for Stage 2, 68% for Stage 3 and 57% for Stage 4, respectively (Figure, log-rank test p=0.001). Cumulative death rates after re-staging Conclusion In a real-world registry of patients with moderate AS patients, worsening extra-aortic valvular cardiac damage portends a worse long-term prognosis.

A: AORTIC STENOSIS: QUANTIFICATION OF DIFFUSE FIBROSIS, EXAMINATION OF MYOCARDIAL PHYSIOLOGY AND RESPONSE TO RAMIPRIL

<h3>Introduction</h3> The physiological response of the myocardium to pressure overload is important in determining outcome in aortic stenosis (AS). It may be modified by inhibition of the renin-angiotensin system. We used cardiac magnetic resonance (CMR) to assess diffuse myocardial fibrosis (DMF), myocardial physiology and the response to Rampril in AS. <h3>Methods</h3> <i>DMF in AS</i> 24 symptomatic patients with severe AS underwent myocardial biopsy at the time of aortic valve replacement (AVR). 85 asymptomatic AS patients and 33 matched controls were recruited. All subjects underwent CMR scanning at 1.5 for T1 mapping. <i>Myocardial physiology in moderate AS</i> 31 patients with moderate asymptomatic AS and 12 matched normal controls underwent CMR scanning at 1.5 T for measurement of strain, perfusion and T1 values. <i>Ramipril in Asymptomatic AS</i> A double-blinded, placebo-controlled, randomized, prospective trial was carried out. 100 patients with moderate or severe asymptomatic AS and normal LV function were randomized to Ramipril 10 mg od (n=50) or placebo (n=50) for a year. 95 patients underwent CMR scanning (LV mass, function, strain, perfusion, T1 mapping), echocardiography and exercise testing at 0, 6 and 12 months. <h3>Results</h3> <i>DMF in AS</i> There was a significant correlation between CMR T1 values and collagen vascular fraction (CVF)% (r=0.65, p=0.002) from biopsy. Mean T1 values were significantly longer in all groups with severe AS (972±33 ms in severe asymptomatic, 1014 ±38 ms in severe symptomatic) than in normal controls (944±16 ms) (p&lt;0.05) (Figure&nbsp;1). The strongest associations with T1 values were for aortic valve area (r=−0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008). <i>Myocardial physiology in moderate AS</i> There was a significant reduction in perfusion and longitudinal strain (LS) in moderate AS patients compared to normals; myocardial perfusion index 1.9±0.2 in normals, 1.3±0.4 in AS and LS -15±1 in normals, -11±2 in AS. (both p&lt;0.001). There was a moderate correlation between LS and perfusion (r=-0.4 p&lt;0.05). <i>Ramipril in Asymptomatic AS</i> Data was available in 78 patients for the primary endpoint (LV mass) at 12 months. There was reduction in LV mass in the Ramipril compared to placebo group; −3.96g (CI: −8.55, 0.62) p=0.089 at 6 months and −8.36g (CI:−14.22, −2.51) p=0.006 at 12 months. Figure&nbsp;2. There was a trend towards reduction in valve area (p=0.067), peak aortic velocity (p=0.056) and fewer deaths in the Ramipril group after completion of the trial (p= 0.074). <h3>Conclusion</h3> DMF in AS may be assessed noninvasively using CMR. DMF increases with severity of the AS and LV hypertrophy. Significant changes in perfusion and LS already exist in moderate AS, indicating that significant myocardial changes occur early in the disease process. Rampril 10 mg over a year led to a significant reduction in LV mass in the treated group. A larger multi-centre clinical outcome trial is required to determine whether this translates into clinical benefit.

Does Mitral Stenosis Impact Exercise Capacity in Children with Mild to Moderate Aortic Stenosis?

PURPOSE: Mild to moderate aortic stenosis does not typically impact exercise capacity in children. The purpose of this study was to determine the impact of mitral stenosis (MS) on exercise capacity in patients with mild to moderate aortic stenosis (AS). METHODS: Isolated mild to moderate AS patients and combined MS/AS patients underwent maximal exercise echocardiography using the James protocol. Subjects with structurally normal hearts (Norm) served as controls. Baseline and peak exercise data and echo valvar gradients were compared using one-way ANOVA and the Bonferroni t procedure. RESULTS: 13 studies in 10 patients with isolated AS (mean age 15.3 years) were compared to 13 studies in 8 patients with combined MS/AS (mean age 14.6 yrs) and 26 normal subjects (mean age 14.2 yrs). Demographics, total working capacity (TWC), maximal systolic blood pressure (SBP) and respiratory quotient (MaxRQ) were not significantly different among the groups. There was no significant change in mean aortic gradient from rest to peak exercise in MS/AS and AS groups (19±11 to 29±9, 25±11 to 24±15mmHg). There was a significant increase in mean mitral gradient from rest to peak exercise in the MS/AS group (5±2 to 16±8 mmHg, p<0.001). The MS/AS group demonstrated a significantly decreased MaxHR compared to Norm and significantly decreased maximal oxygen consumption (MVO2) and cardiac output (MaxQ) compared to both AS and Norm groups.TableCONCLUSION: In pediatric patients with mild to moderate aortic stenosis, the presence of mild mitral stenosis negatively impacts aerobic capacity and cardiac output at peak exercise. This suggests the possibility that mitral stenosis perturbs the adaptive mechanisms utilized by these subjects during peak exercise.