Moderate Aortic Stenosis Research Articles

Prognostic value of aortic valve area normalized to body size in native aortic stenosis

Introduction and objectivesAlthough guidelines recommend the use of a cutoff value of 0.60 cm2/m2 for aortic valve area (AVA) normalized to body surface area (BSA) for severe aortic stenosis, there is little evidence of its prognostic value. Our aim was to test the value of AVA normalized to body size for outcome prediction in aortic stenosis. MethodsOne-hundred and ninety patients with at least moderate aortic stenosis (AVA <1.50 cm2) were prospectively enrolled. AVA was normalized to BSA and height. The primary endpoint was cardiovascular death under medical management. A receiver operating characteristic curve was plotted to determine the best cutoff value for predicting cardiovascular death. ResultsAn AVA/BSA cutoff value of 0.50 had a sensitivity of 96% and specificity of 51%. An AVA/height cutoff value of 0.49 showed a sensitivity of 96% and a specificity of 52%. During a mean follow-up of 247±190 days, there were 24 cardiovascular deaths, with higher cardiovascular mortality in patients with AVA/BSA <0.50 cm2/m2 (21% vs 2.5%, P <.001) and AVA/height <0.49 cm2/m (25% vs 12%, P <.001). Two-year survival was 95±5% in patients with AVA/BSA> 0.50 cm2/m2 and was 37±5% in patients with AVA/BSA <0.50 cm2/m2 (P <.001). Cardiovascular death risk was higher in patients with AVA/BSA <0.50 cm2/m2 (adjusted 10.9 [1.2-103.7], P=.037), but cardiovascular mortality was not significantly higher in multivariate analysis for patients with AVA/height <0.49 cm2/m (2.0 [0.6-6.0], P=.22). ConclusionsWe could identify a subgroup of patients at high risk of cardiovascular death when they were medically treated. Consequently we recommend using an AVA/BSA cutoff value of 0.50 cm2/m2 to identify a subgroup of patients with higher cardiovascular risk.

Staging Cardiac Damage in Patients With Hypertension

Ventricular and extraventricular response to pressure overload may be a common process in aortic stenosis and hypertension. We aimed to evaluate the association of a newly defined staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, with long-term outcomes in patients with hypertension. We retrospectively analyzed 1639 patients with hypertension who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a Japanese hospital, after excluding severe and moderate aortic stenosis, aortic regurgitation, mitral stenosis, previous myocardial infarction, or cardiomyopathy. We classified patients according to the presence or absence of cardiac damage as detected on echocardiography as follows: stage 0, no cardiac damage (n=858; 52.3%); stage 1, left ventricular damage (n=358; 21.8%); stage 2, left atrial or mitral valve damage (n=360; 22.0%); or stage 3 and 4, pulmonary vasculature, tricuspid valve, or right ventricular damage (n=63; 3.8%). The primary outcome was a composite of all-cause death and major adverse cardiac events. Cumulative 3-year incidence of the primary outcome was 15.5% in stage 0, 20.7% in stage 1, 31.8% in stage 2, and 60.6% in stage 3. After adjusting for confounders, the stage was incrementally associated with higher risk of the primary outcome (per 1-stage increase: hazard ratio, 1.46 [95% CI, 1.31-1.61]; P<0.001). The staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, was associated with long-term outcomes in patients with hypertension in a stepwise manner.

Hypertension in aortic stenosis: relationship with revealed symptoms and functional measures on treadmill exercise.

The impact of hypertension on symptoms and functional capacity during exercise treadmill test (ETT) in apparently asymptomatic patients with aortic stenosis is poorly understood. A total of 314 patients (age 65 ± 12 years, 68% men) with moderate or severe asymptomatic aortic stenosis underwent baseline echocardiography and ETT. Hypertension was defined as a history of elevated blood pressure (BP), past or current treatment with antihypertensive agents or a BP at the baseline clinic visit more than 140/90 mmHg. There were 229 (73%) patients with hypertension who were older, more likely to have diabetes, hypercholesterolemia and coronary artery disease, larger left atrial diameters, higher left ventricular (LV) mass and a higher proportion of LV hypertrophy than normotensive patients. In a univariate logistic regression analysis hypertension and clinic SBP were not associated with revealed symptoms. In a multivariate logistic regression analysis, lower peak SBP [odds ratio (OR) 1.02;95% confidence interval (CI) 1.00-1.04, P = 0.017] and rapid early rise in heart rate (OR 15.03; 95% CI 6.23-36.24, P < 0.001) were associated with a higher risk of revealed symptoms while the use of antihypertensive treatment was associated with a lower risk of revealed symptoms (OR 0.40; 95% CI 0.18-0.89, P = 0.025), independent of age, obesity, LV ejection fraction and aortic valve area. In a linear regression analysis, after adjustment for age, sex and BMI, hypertension did not retain an association with lower metabolic equivalents (β = -0.06, P = 0.311). Hypertension in aortic stenosis patients was associated with a high cardiovascular disease burden, but did not interact with symptoms or functional capacity during ETT. Hypertension does not interfere with the clinical interpretation of exercise testing.

Cardiac and extra-cardiac pathologies in patients with acute arterial occlusion

We aimed to investigate cardiac and extra-cardiac pathologies in patients who were operated for acute arterial occlusion. Between March 2010 and March 2018, a total of 120 patients who underwent surgical treatment for acute arterial occlusion were included in this retrospective study. 84 (70%) and 27 (22. 5%) of the patients had cardiac and extra-cardiac pathologies, respectively. In 9 (7. 5%) of the cases, no reason for arterial occlusion could be found. Pure atrial fibrillation was found in 39 (32. 5%) patients. Atrial fibrillation and cardiac valvular pathologies were detected in 45 patients (37. 5%). Among those with a cardiac valvular pathology, 9 patients (7. 5%) had pure mitral stenosis, 21 patients (17. 5%) had moderate to advanced mitral stenosis with tricuspid regurgitation, 9 patients (7. 5%) had 20-30 mitral regurgitation with 30 tricuspid regurgitation, 3 patients (2. 5%) had moderate mitral stenosis, 30-40 tricuspid regurgitation and 20-30 aortic stenosis, and 3 patients (2. 5%) had 30 mitral regurgitation, 10- 20 tricuspid regurgitation, calcific moderate aortic stenosis, and coronary artery disease. Among those 27 patients with an extra-cardiac pathology, 21 patients (22. 5%) had peripheral artery disease, 3 patients (2.5%) had an abdominal aortic aneurysm, and 3 patients (2. 5%) had Behçet's Disease. Cardiac and extra-cardiac pathologies should be kept in mind in patients with acute arterial occlusion. Thus, detected pathologies could be treated, and the development of additional peripheral emboli could be prevented.

Impact of estimated left atrial volume on prognosis in patients with asymptomatic mild to moderate aortic valve stenosis

BackgroundThe prognostic impact of increased left atrial (LA) volume in mild-to-moderate aortic valve stenosis (AS) is unclear. We investigated the association of estimated LA volume with prognosis in a large prospective study of patients with asymptomatic mild-to-moderate AS. MethodsThe association of estimated LA volume with major cardiovascular events (MACE, combined cardiovascular death, heart failure hospitalization and non-hemorrhagic stroke) was assessed in 1534 patients with initially mild-to moderate asymptomatic AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis study for a median of 4.3 years. LA volume was estimated from LA diameter applying a validated nonlinear equation and indexed to body height in meters squared (eLAVI). An enlarged eLAVI was identified by using sex-specific cut-offs (>19 ml/height2 in men and >17 ml/height2 in women). ResultsPatients with enlarged eLAVI were older, more obese, and had higher systolic blood pressure and left ventricular (LV) mass index (all p < 0.001). During follow-up, incident MACE occurred in 137 patients, more often in patients with enlarged eLAVI (20% vs. 7.7%, p < 0.001). Using aortic valve replacement as a competing risk event, enlarged eLAVI at baseline predicted increased hazard rate (HR) of MACE (HR 2.21 [95% confidence interval 1.37–3.55], p = 0.001) independent of significant associations with presence of LV hypertrophy, older age, higher peak aortic jet velocity, serum creatinine and lower LV ejection fraction and stroke volume. ConclusionsPresence of enlarged eLAVI was independently associated with increased risk of MACE in patients with mild-to moderate asymptomatic AS.

Clinical and Echocardiographic Predictors of Outcomes in Patients With Moderate (Mean Transvalvular Gradient 20 to 40 mm Hg) Aortic Stenosis

Risk factors for adverse clinical outcomes in patients with moderate aortic stenosis are not well defined. Previous studies have suggested that certain patients with moderate AS may be at an increased risk of heart failure (HF) or death. All patients with moderate AS seen in our institution during the study period (6/1/2014 to 6/30/2017) with a minimum 1-year follow-up were included. Clinical and echocardiographic data were collected retrospectively. End points were defined as HF hospitalization, aortic valve replacement (AVR), or death. Kaplan-Meier and multivariable Cox proportional hazard models analyses were conducted using composite outcomes of (1) HF hospitalization or AVR and (2) HF hospitalization, AVR, or all-cause death. A total of 151 subjects met the inclusion criteria. The most significant risk factors associated with the composite outcomes were an ejection fraction (EF) <50% ((1) hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.34, 7.12; (2) HR: 3.8; 95% CI: 2.2, 6.6), atrial fibrillation ((1) HR: 2.0; 95% CI: 1.2, 3.2; (2) HR: 2.1; 95% CI: 1.43, 3.2), left ventricular hypertrophy ((1) HR: 5.85; 95% CI: 2.0, 15.8; (2) HR: 3.2; 95% CI: 1.4, 7.4), aortic valve area ((1) HR: 0.3; 95% CI: 0.1, 0.6; (2) HR: 0.32; 95% CI: 0.1, 0.65), and abnormal right ventricular function ((1) HR: 4.3; 95% CI: 2.5, 7.5; (2) HR: 5.5; 95% CI: 3.0, 9.8). In conclusion, presence of reduced ejection fraction, atrial fibrillation, left ventricular hypertrophy, and abnormal right ventricular function are associated with an increased risk of HF hospitalization, AVR, and death in patients with moderate aortic stenosis.

6098The role of diastolic function in risk stratification of patients with moderate aortic stenosis

Abstract Background Currently data on the risk stratification of patients with moderate aortic stenosis (AS) are very limited. Method Patients diagnosed with moderate AS in 2012 (aortic valve area [AVA]: &gt;1 and ≤1.5cm2) were identified. Patients were stratifying by LV diastolic function (normal vs high filling pressure), left ventricular ejection fraction (LVEF ≥50 vs &lt;50%) and stroke volume index (SVI ≥35 vs &lt;35 ml/m2). High filling pressure was defined as average E/e' ≥14 or septal E/e' ≥11 when atrial fibrillation was present. The prognosis was compared to age- and sex-matched general population. Results 898 patients were included (age 74 years, 58% male, AVA 1.25 cm2). During a median follow-up of 2.9 years, there were 346 deaths. In patients with moderate AS, mortality was higher than expected (P&lt;0.001, Fig 1A). LV high filling pressure, LVEF&lt;50% and SVI&lt;35ml/m2 were present in 416 (55%), 140 (17%) and 81 (9%) patients, respectively. Those with normal filling pressure had similar prognosis when compared to controls (Fig 1C, P=0.35); whereas mortality rates remained higher than reference even when LVEF≥50% or SVI≥35ml/m2 (Fig 1E, 1G, P&lt;0.001). Amongst all groups, mortality rates were the highest in patients with LVEF &lt;50% or SVI &lt;35 ml/m2 (Fig 1D, 1F, P&lt;0.001); mortality ratios were 3.78 (95% CI 3.01–4.67) and 6.91 (95% CI 5.13–9.11), respectively. Noteworthy, high filling pressure allowed further risk stratification when LVEF or SVI was preserved (Fig 2, P&lt;0.001). Figures 1 &amp; 2 Conclusions Patients with moderate AS showed poor survival. A clinical trial examining role of aortic valve replacement would be beneficial not only in patients with reduced LVEF or SVI but also in those with high LV filling pressures.

P2650Antihypertensive treatment with calcium channel blockers in patients with moderate or severe aortic stenosis: relationship with all-cause mortality

Abstract Background Hypertension is prevalent in patients with aortic stenosis (AS) and optimal blood pressure (BP) control is advised to reduce arterial load and avoid cardiovascular events. Whether calcium channel blockers (CCB) are safe is not known. Methods A total of 314 patients (age 65±12 y, 68% men) with moderate or severe asymptomatic AS were included. Results The prevalence of hypertension was 73.6%, and 65% took antihypertensive treatment. Patients who used a CCB (25%) (CCB+) were older, had higher clinic systolic BP, were more likely to have hypercholesterolemia and coronary artery disease (CAD), and to use a diuretic or alpha blocker compared to CCB- patients (all p&lt;0.05) (Table). During the baseline ETT, patients who used a CCB achieved a lower peak heart rate, a shorter exercise time and were more likely to have a blunted BP response compared to those who did not use a CCB (all p&lt;0.05) (Table). Event-free survival was significantly lower in CCB+ than CCB- patients (Fig) (all-cause mortality 16 [20.3%] versus 13 (5.6%); p&lt;0.001). In a multivariable Cox regression model, CCB+ was associated with a 6.8-fold increased hazard ratio (HR) for all-cause mortality (HR 6.77 95% CI 1.66–27.54, p=0.008), independent of age, gender, systolic BP, hypertension, diabetes, CAD, hypercholesterolemia and aortic valve area. Table 1. Baseline characteristics of patients CCB− (n=234) CCB+ (n=80) p Age, y 64±12 70±10 &lt;0.001 CAD, % 45 66 0.006 Hypercholesterolemia, % 62 78 0.015 Clinic systolic BP, mmHg 139±19 150±17 &lt;0.001 Left atrial diameter, cm 3.7±0.7 3.9±0.6 0.007 LV end-diastolic diameter, cm 4.5±0.7 4.8±0.6 0.002 LV mass index, g/m2.7 50±17 57±17 0.007 Aortic valve area, cm2 0.94±0.22 0.93±0.22 0.716 LV stroke work, g-m/bmp 155±46 175±69 0.046 Peak HR at baseline ETT, bmp 138±24 120±25 &lt;0.001 Blunted BP response, % 33 49 0.013 Exercise duration, min 10.1±4.5 8.3±3.7 0.001 Double Product, mmHg·bmp 1.85±0.43 2.08±0.54 &lt;0.001 Figure 1 Conclusion The use of calcium channel blockers was associated with an adverse effect on treadmill exercise and reduced survival in apparently asymptomatic patients with moderate or severe AS. Acknowledgement/Funding None

P3694Discordant criteria in moderate aortic stenosis patients: prognostic implications

Abstract Background The frequency of discordant mean valve gradient (MG) and aortic valve area (AVA) in patients with moderate aortic stenosis (AS) has not been investigated. Objectives Determine the occurrence of discordant gradient in patients with moderate AS (defined by MG &lt;20 mmHg), and how these patients compare with concordant gradient moderate AS (MG &gt;20 mmHg) in terms of patients' characteristics and the impact on long term prognosis. 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 discordant or concordant gradients, MG &lt;20 mmHg or &gt;20 mmHg, respectively. The clinical endpoint was all-cause mortality. Results Of 522 patients with moderate AS, 95 (18.2%) had discordant gradient moderate AS (MG &lt;20 mmHg). Patients with discordant mean gradient were older, had higher prevalence of previous myocardial infarct, larger left ventricular (LV) end-diastolic volume index, lower LV ejection fraction (EF), stroke volume index and higher LV filling pressure. Compared to patients with concordant gradients, these patients had higher mortality rates (57.9% vs 46.6%, p=0.05) and lower aortic valve replacement rates (33.7% vs 54.9%, p&lt;0.001) during a median follow-up of 6.2 [IQR 3.2–9.0] years. The results of Cox regression analysis are shown on the table. Cox proportional hazard analysis All-cause mortality Univariate analysis Multivariate analysis Hazard ratio (95% CI) P value Hazard ratio (95% CI) P value Age (per 1 year increase) 1.05 (1.03–1.06) &lt;0.001 1.04 (1.02–1.06) &lt;0.001 Diabetes (yes/no) 1.34 (1.03–1.74) 0.031 1.33 (0.97–1.82) 0.072 Previous myocardial infarction (yes/no) 1.73 (1.29–2.34) &lt;0.001 1.01 (0.70–1.46) 0.980 eGFR &lt;60 ml/min/1.73m2 (yes/no) 2.15 (1.68–2.76) &lt;0.001 1.71 (1.25–2.33) 0.001 Left ventricular hypertrophy (yes/no) 1.74 (1.31–2.30) &lt;0.001 1.50 (1.07–2.09) 0.018 Indexed LA volume (per 1 mL/m2 increase) 1.005 (1.001–1.009) 0.008 1.006 (1.001–1.012) 0.040 Tricuspid regurgitation &gt;moderate (yes/no) 2.02 (1.29–3.16) 0.002 1.36 (0.73–2.54) 0.337 Discordant moderate AS (yes/no) 1.81 (1.34–2.45) &lt;0.001 1.42 (1.01–2.01) 0.049 AS, aortic stenosis; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; LA, Left atrial. Conclusion Discrepant aortic mean gradient in moderate AS is not uncommon and occurs more often in older patients, with higher LV filling pressure and lower EF and stroke volume index. The lower gradient values lead to underestimation of AS severity, and is associated with greater cardiac extra-valvular damage and higher mortality.

LEFT VENTRICLE EFFICIENCY IN CHILDREN WITH MODERATE AORTIC VALVE REGURGITATION OR MODERATE AORTIC VALVE STENOSIS

Patients with congenital aortic valve disease can remain asymptomatic. But the risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe aortic valve disease (stenosis or regurgitation) is clearly defined, but the optimal timing for moderate aortic valve disease (moderate aortic stenosis (mod AS) or moderate aortic regurgitation modAR) remains unknown and largely unexplored. The specific objective of this work is to develop a mathematical model in order to evaluate left ventricle performance in patients with moderate aortic valve disease. Thirty pediatric patients were included in this study (healthy = 10; modAS = 11; modAR = 9). A mathematical model has been developed to evaluate patient-specific LV performance. In addition, we have developed a new non-invasive parameter, LV efficiency, evaluating the effect of aortic stenosis and aortic regurgitation on LV function: Elv=(1-Rf)*(Psys/(Psys+TPGmean)) where Rf is the regurgitant fraction, Psys is the systolic arterial pressure and TPGmean is mean transvalvular pressure gradient. Our results show that healthy patients possess a very high LV efficiency (96.4±1.9%). However, modAS patients have a significant reduction in their LV efficiency (82.7±8.4%, p < 0.05). Interestingly, the modAR group was found to have the lowest LV efficiency (72.5±7.3%, p < 0.05). Patients with aortic valve disease even at a moderate severity should be carefully followed because their LV performance is significantly reduced compared to healthy patients. The evaluation of LV efficiency offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

4309Structural or functional left sided heart disease found on echocardiographic screening is associated with a higher risk of death in patients with end stage renal disease receiving haemodialysis

Abstract Introduction Cardiovascular disease is the leading cause of death in patients with end-stage renal disease on haemodialysis. Guidelines recommend echocardiography in all incident patients on dialysis and every three years, or when considered for kidney transplantation. The prognostic value of significant valve disease or reduced systolic function detected by echocardiographic screening is however not clear. Purpose We aimed to test the hypothesis that structural heart disease in an unselected, contemporary population of patients on maintenance dialysis is associated to a higher risk of death. Methods Adult chronic haemodialysis patients in two large dialysis centers had transthoracic echocardiography performed immediately prior to dialysis and were followed prospectively. Significant structural or functional left sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%. Results Among the 247 included patients (66 [IQR 64–67] years of age, 68% male), 54 (22%) had significant structural or functional left sided heart disease. An LVEF ≤40% was observed in 31 patients (13%). Severe or moderate aortic stenosis was present in 4 (2%) and 16 (7%) patients respectively, moderate mitral regurgitation in 4 (2%) patients and mitral stenosis in one (0.4%) patient. In more than half of the patients (56%), significant structural or functional left sided heart disease was not recognized prior to the study. After 2.8 years of follow-up, all-cause mortality was 52% for patients with significant heart disease and 32% for patients without significant structural heart disease (hazard ratio [HR] 1.95 (95% CI 1.25–3.06) (Figure). On multivariable adjusted Cox proportional hazard analysis, including age, sex, ischemic heart disease, diabetes, hypertension and time on dialysis, structural heart disease was an independent predictor of mortality with a HR of 1.60 (95% CI 1.01–2.55) along with age (HR per year 1.05 [95% CI 1.03–1.07]). Kaplan-Meier estimate of survival Conclusion Left ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage renal failure on haemodialysis and are associated with a higher risk of death.

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.

P6474Hidden in plain sight: diastolic blood pressure, resting heart rate and physical examination are independent predictors of mortality in chronic aortic regurgitation

Abstract Background In patients with hemodynamically-significant chronic aortic valve regurgitation (AR), the prognostic significance of routinely-measured diastolic blood pressure (DBP), resting heart rate (RHR) and physical examination signs of heart failure (HF), is unknown. Purpose To investigate the association of DBP, RHR and HF signs, with all-cause mortality. Methods This retrospective cohort study included all consecutive patients with moderately-severe or severe AR within a tertiary-referral center from 2006–2017. Patients with ≥moderate aortic stenosis and those with ≥moderate mitral stenosis/regurgitation were excluded. Results Of 820 patients (age 59±17 years; 82% men) with DBP 64±13mmHg and RHR 64±12bpm, followed for 5.5±3.5 years, 104 died under medical management and 400 underwent aortic valve surgery (AVS). In multivariable analysis, DBP (adjusted-hazard ratio [HR] 0.82 [0.68–0.98] p=0.031, per 10mmHg increase), RHR (adjusted HR 1.2 [1.01–1.41] p=0.034 per 10bpm increase), and any HF signs (adjusted HR 1.66 [1.04–2.61] p=0.032) were associated with all-cause death independently of demographics, comorbidities, and guideline-derived surgical triggers. Mortality increased in a J-curve fashion for DBP starting at 70 mmHg and peaking at 55 mmHg (Fig A,C), and in a linear fashion for RHR starting at 60bpm (Fig B, D). The association persisted after additional adjustment for medications, presence of hypertension and time-dependent AVS. A clinical score combining DBP, RHR and any HF signs increased the mortality risk-discrimination of demographics and comorbidities from 74% to 79% (p=0.01), and from 79% to 82% after addition of surgical triggers (p=0.04). Figure. Risk of death by DBP and RHR Conclusions In patients with AR, routinely-measured vital signs and physical examination are strongly associated with all-cause mortality; lower DBP, higher RHR and any HF signs are independent predictors of mortality, and provide incremental mortality risk-discriminating value to baseline demographics, comorbidities and guideline-derived surgical triggers. These findings represent a clinical paradigm shift and have guideline implications.

P1778Changes in size of ascending aorta in patients with bicuspid aortic valves

Abstract Introduction It is well known that bicuspid aortic valve (BAV) is associated with premature valve dysfunction and ascending aorta dilation. However, limited data still exists regarding the rate of growth of the ascending aorta and the risk factors associated with it in these patients. Methods We analyzed prospectively baseline characteristics and echocardiographic data from 192 adult patients with BAV followed in an Adult Congenital Heart Disease Unit from 2007 until 2018. The exclusion criteria were: patient's without at least 2 echocardiographic examinations &gt;6 months apart, and patients with aortic valve and/or ascending aorta surgery at baseline o at follow up (except aortic coarctation). Following the ASE guidelines two cardiologists experts in echocardiography made all the studies at baseline and follow-up where they measured the aortic root and ascending aortic diameters, as well as typified the aortic valve and analyzed the degree of stenosis (AS) and regurgitation (AR). Statistical analysis was performed using Stata 13.1, and a p value of ≤0.05 was considered significant. Results 97 patients were finally included (70 male, mean age 37.56±18.9 years). 66 patients had type A BAV (68.04%), 21 type B (21.7%), 2 type C (2.06%) and 7 unicuspid (7.22%). 19 patients had hypertension (19.59%) and 9 had a corrected aortic coarctation. In baseline echocardiogram, 20 had aortic stenosis ≥ moderate (20.6%) and 38 regurgitation ≥ grade II (39.18%). Mean diameter of ascending aorta was 35.78mm ± 6.73. With a mean follow-up time of 50.53±27.05 months, mean rate of diameter progression was 0.76 mm/year at the proximal ascending aorta (95% CI 0.6 to 1.2). Progression was significantly higher in patients with moderate or severe aortic stenosis (0.65 vs. 1.17 mm/year, p=0.021). Age, sex, hypertension, AR and high baseline diameters (≥40mm or ≥45mm) were not associated with progression. In a direct comparison between the two more frequent forms of BAV, Type A and Type B, rate of diameter progression was significantly higher in Type B (0.61 vs. 1.05 mm/year, p=0.044). In a multivariate analysis, none of the variables statistically associated to major progression were found to be predictors of growth of the ascending aorta. Conclussions In our population of BAV patients, mean rate of diameter progression at the proximal ascending aorta was 0.76 mm/year. Moderate-severe AS, and having type B BAV were associated, but not predictors, of higher growth rates.

P5993Comprehensive characterization of experimental aortic valve stenosis by multiparametric MRI

Abstract Background Recently, we established an experimental model of moderate aortic valve stenosis (AS) aiming to mimic human disease progression closely. Functional and structural MRI of a mouse model in experimental aortic valve stenosis has not been accomplished so far. Purpose Here, we aimed at developing comprehensive MRI approach for simultaneous assessment of changes in valvular, left ventricular and aortic morphology and function. Methods Male 12-week-old wildtype mice (C57Bl/6) were subjected to wire injury of the aortic valve to induce aortic valve stenosis. High resolution MRI at 9.4T was used to monitor subsequent functional and structural changes in the aortic valve, the ascending aorta, the left ventricle and aortic flow patterns. Results MRI permits accurate planimetry of the orifice and the thickness of the aortic valve, allows a reliable three-dimensional mapping of transvalvular aortic flow, simultaneously depicts aortic regurgitation in 3D fashion and permits assessment of left ventricular changes due to AS. In our model we observed a reduced valve orifice and an increase in valve thickness. Homogenous flow pattern under control converted to heterogenous and turbulent flow with progression of AS associated with increased aortic strain, aortic wall and left ventricular wall thickness. Conclusions In a murine model of aortic valve stenosis MRI is capable to reliably display a three-dimensional transvalvular aortic flow profile with concomitant quantification of structural and functional changes in aortic valve, left ventricle, and ascending aorta. This comprehensive functional imaging at high resolution and distinct reproducibility offers for the first time serial assessment of disease progression in an experimental model of aortic valve stenosis.

P3373Predictors of dilatation of ascending aorta in patients with bicuspid aortic valve, a longitudinal multicenter study

Abstract Introduction The bicuspid aortic valve (BAV) is frequently associated to dilation of the ascending aorta. Some cross-sectional studies have related the aortic dilation with morphotype and valvular dysfunction. The aim of this longitudinal multicenter study was to analyze the progression of the aortic dilation and to identify its predictors. Methods We included 459 patients (mean age 52±17; 325 men 70.8%) with BAV, without aortic coarctation. The BAV morphotype, significant valvular dysfunction and dilation of the aortic root and ascending aorta were established by echocardiography. The patients were followed annually, with an average of 7.5±3.2 years. Results 77% of the patients had BAV with a fusion between left and right cusps, 21% between right and non coronary cusps and 2% between left and non coronary cusps, with a raphe in 77% of these patients. Risk factors included: 35% hypertension, 20% smoking, 5% diabetes and 18% dyslipidemia. The baseline study showed a maximum root diameter of 36±6.2 mm and ascending aorta of 39±8.1 mm. In 7% the aortic root was&gt;45 mm, while in 32% the ascending aorta&gt;45 mm. There was no valvular dysfunction in 17% of patients, while the 8% had significant aortic stenosis and 35% significant aortic regurgitation. The annual growth of the aortic root was 0.33±0.2 mm and for the ascending aorta was 0.38±0.3 mm. At the end of follow-up, 16% of the patients had a root&gt;45 mm and 41% an ascending aorta&gt;45 mm. The annual progression of aortic diameters was not related to valvular morphotype, valvular dysfunction or cardiovascular risk factors. The univariate analysis showed a significant relationship between the annual growth of the aortic root and arterial hypertension (p=0.028) and the annual growth of the ascending aorta with the male sex (p=0.019), smoking (p=0.046) and significant (moderate or severe) aortic stenosis (p=0.013). Diabetes mellitus and the presence of raphe were found to be slightly protective (p=0.049 and p=0.031, respectively). In the multivariate analysis, only the male sex and significant aortic stenosis were independent predictors of dilation of the ascending aorta. Conclusions In patients with bicuspid aortic valve, the progression of the dilation of the aortic root is related to hypertension and the growth of the ascending aorta with the male sex and the presence of significant aortic stenosis. Both bicuspid valve morphotype, basal aortic diameter or age were not related to the progression of aortic dilation.

P2270Clinical characteristics and outcomes after TAVI in patients reclassified to moderate aortic stenosis by integration of multimodality imaging and pressure recovery

Abstract Background Accurate assessment of aortic stenosis (AS) severity is critical for the correct management of patients. This has become particularly important because the introduction of transcatheter aortic valve implantation (TAVI) has markedly increased the number of patients eligible for aortic valve replacement Aims To assess whether reclassification of aortic stenosis (AS) grading by integration of fusion imaging using data from transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) under consideration of the energy loss index (ELI) predicts outcome in patients undergoing transcatheter aortic valve implantation (TAVI). Methods 197 consecutive patients with symptomatic severe AS undergoing TAVI at our University Heart Center were included in this study. AS severity was determined according to current guidelines. Results Left ventricular outflow tract (LVOT) area derived from TTE was smaller than the planimetric area in MDCT due the ovoid shape of the LVOT (3.4±0.12 cm2 vs. 4.5±0.23 cm2; p&lt;0.01). The sinotubular junction (ST-junction) diameter measured in TTE was similar to maximal, minimal, and mean diameters determined by MDCT. The sphericity index confirmed an almost circular anatomy of ST-junction, and its area derived from TTE was similar to the planimetric area in MDCT. Fusion aortic valve area index (fusion AVAi) assessed by inserting MDCT derived planimetric LVOT area in the continuity equation was significantly higher in all patients compared to conventional AVAi. 62 patients were reclassified from severe to moderate AS because fusion AVAi was &gt;0.6 cm2/m2. ELI was calculated for conventional AVAi and fusion AVAi each with ST-junction area determined by both TTE and MDCT. Calculating ELI with fusion AVAi resulted in significantly larger effective orifice area, with values &gt;0.6 cm2/m2 in 83 patients (ST-junction area from echo) and 85 patients (ST-junction area from MDCT). Similarly, calculating ELI with conventional AVAi resulted in significantly larger effective orifice area as compared to AVAi alone. Reclassified patients had lower mean transvalvular pressure gradients, lower myocardial mass, less symptoms according to NYHA classification, and lower proBNP levels at baseline. While both groups exhibited improvement of functional status at 1 year of follow-up, the survival rate at 3 years after TAVI was higher in patients reclassified to moderate AS (81% versus 66%; p=0.02). Conclusion Integration of TTE and MDCT derived values for calculation of ELI reclassifies the severity of AS in 43% of patients initially diagnosed with severe AS.Although reclassified patients display less advanced valve disease at baseline, TAVI results in functional improvement in all patients. Furthermore, patients reclassified to moderate AS exhibit higher survival rates at 3 years after aortic valve replacement.

6099Impact of aortic valve replacement on outcomes of patients with low-flow, low-gradient moderate aortic stenosis

Abstract Background Aortic valve replacement (AVR) is recommended for patients with low-flow, low-gradient (LFLG) and true-severe aortic stenosis (TSAS). However, there is very few data on the potential benefit of AVR in patients with LFLG pseudo-severe (i.e. moderate) AS (PSAS). Methods Consecutive patients with aortic valve area ≤0.6 cm2/m2, mean gradient &lt;40 mmHg were prospectively recruited in a multicenter observational cohort study. The patients were categorized in TSAS vs. PSAS using previously reported thresholds of flow-independent parameters of AS severity (projected valve area at normal flow rate ≤1.0 cm2 and/or aortic valve calcium score by CT &gt;1200 AU in women and &gt;2000 AU in men). To account for between-treatment-group differences, inverse probability-of-treatment weighting was combined to Cox proportional hazards regression. Results Among the 430 patients included in this study, 297 (69%) were classified as TSAS and 274 (57%) underwent AVR. Of note, 21% of the patients treated by AVR were classified as PSAS. In patients managed conservatively (ConsRx), 52% had PSAS and 48% TSAS. During a median follow-up of 28 months [8–60], 198 patients died. The adjusted weighted hazard ratio (awHR) of death associated with AVR as compared to ConsRx was 0.42 [0.24–0.73] (p&lt;0.0001, Figure1-Panel-A). This survival benefit associated with AVR was observed not only in patients with TSAS but also in those with PSAS (awHR: 0.29 [0.12–0.70]; p=0.006, Figure1-Panel-B). Figure 1 Conclusion The results of this study suggest that AVR is associated with a survival benefit not only in LFLG patients with TSAS but also in those with PSAS. Randomized trials are needed to confirm the benefit of AVR in patients with moderate AS and depressed LV systolic function. Acknowledgement/Funding Canadian Institute of Health Research

226Earlier surgical myectomy vs. waiting for a Class I indication is associated with improved long-term survival in symptomatic hypertrophic obstructive cardiomyopathy patients

Abstract Background In patients with severe hypertrophic obstructive cardiomyopathy (HOCM), surgical myectomy (SM) is typically indicated for severe symptoms despite maximal medical therapy. Aims We sought to compare long-term outcomes of severe HOCM patients where decision for SM was based on guideline-recommended Class I indication (functional Class or FC ≥3 or exertional syncope despite maximal medical therapy) vs. earlier (FC II and/or impaired exercise capacity on exercise echo with medication intolerance). Methods The study included 2268 HOCM patients (excluding &lt;18 years, at least moderate aortic stenosis requiring valve replacement and subaortic membrane, age 56±14 years, 55% men), who underwent SM at our center between 1/02–3/18. Clinical and echo data, including left ventricular outflow tract gradient (LVOTG) were recorded. Cardiac death and/or appropriate internal defibrillator discharge were recorded as composite endpoints. Results 1318 (58%) patients met Class I indication for SM, while the rest underwent SM for FC II (due to medicine intolerance) or impaired exercise capacity. 535 (24%) and 408 (18%) had history of atrial fibrillation and a family history of HCM. All patients were on maximally tolerated medical therapy. European 5-year sudden death risk score was 3.7±2%. Baseline basal septal thickness, resting and maximal LVOTG were 2.0±0.3 cm, 61±44 mm Hg and 100±31 mm Hg. At 6.2±4 years of follow-up after SM, 248 (11%) had composite events (13 [0.6%] in-hospital deaths). Competing risk survival analysis for composite endpoint is shown in Figure 1a. Patients operated for Class I indication had significantly higher longer-term event rate vs. those operated earlier (182 [14%] vs. 66 [7%], p&lt;0.001, Figure 1B). Conclusions In patients with severe HOCM undergoing SM at an experienced center performed by experienced surgeons, delaying surgery till reaching Class I indication was associated with much worse survival than operating earlier for milder symptoms or impaired exercise tolerance on exercise echo.

TCT-429 Development of Moderate or Severe Aortic Stenosis From Significant Aortic Regurgitation: A Different Path to Mixed Aortic Valve Disease

TCT-429 Development of Moderate or Severe Aortic Stenosis From Significant Aortic Regurgitation: A Different Path to Mixed Aortic Valve Disease