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Background: Traditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS)., Aims: To investigate a new classification system for severe AS using phenomapping., Methods: Consecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm 2 were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable., Results: In total, 613 patients were initially recruited, with a mean±standard deviation AVA of 0.72±0.17 cm 2 . Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n=1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46-3.26; P<0.001)., Conclusions: Artificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Aims: To assess rates of reclassification of severity and associated 5-year survival in patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) after application of a CT-derived correction factor (CF) to refine the measurement of aortic valve area (AVA) and stroke volume index (SVi) using Doppler echocardiography., Methods and Results: We enrolled 1450 patients with severe AS and preserved LVEF from a French registry. Multiplication of echocardiographic LV outflow tract diameter by a CT-derived CF of 1.13 to calculate the AVA and SVi using the continuity equation resulted in reclassification of 39% of patients from severe to moderate AS (AVA > 1 cm 2 ) and 77% from low flow (LF, SVi < 35 ml/m 2 ) to normal flow (NF, SVi ≥ 35 ml/m 2 ). After application of the CF, 5-year survival with conservative management was 50 ± 4% for severe AS compared to 62 ± 4% for moderate AS (p < 0.001). A strategy of medical management followed by intervention for severe AS was associated with higher risk of mortality over 5-year follow-up after adjustment for covariates and application of the CF (HR 1.35 [1.10-1.55], p = 0.015). Five-year survival was also poorer in patients remaining in the LF group after application of the CF, even after valve intervention (72%, 66% and 47% for NF to NF, LF to NF and LF to LF, respectively). After adjustment for covariates (including intervention), risk of mortality was higher in LF to LF patients compared to NF to NF (HR 1.78 [1.25-2.56]), but similar for NF to NF and LF to NF (HR 1.20 [0.90-1.60])., Conclusion: Refined accuracy of echocardiographic LV outflow tract diameter measurement using a CF of 1.13 before derivation of AVA and SVi in patients with severe AS and preserved LVEF allows improved grading of severity, and prediction of prognosis. We recommend implementation of the CF during routine echocardiography when using the continuity equation for Doppler haemodynamic measurements., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease., Methods: The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities)., Results: Compared with patients with negative stress results, those with positive stress results (n = 28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7 ± 2.9% vs -19.0 ± 1.9%, P < .001). On multivariable logistic regression analysis, DM duration > 10 years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P < .001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893]., Conclusions: The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial contraction fraction (MCF) is a volumetric measure of myocardial shortening independent of left ventricular size and geometry. This multicenter study investigates the usefulness of MCF for risk stratification in low-gradient severe aortic stenosis with preserved ejection fraction., Methods: We included 643 consecutive patients with low-gradient severe aortic stenosis with preserved ejection fraction in whom MCF was computed at baseline and analyzed mortality during follow-up., Results: Throughout follow-up with medical and surgical management (34.9 [16.1-65.3] months), lower MCF tertiles had higher mortality than the highest tertile. Eighty-month survival was 56±4% for MCF>41%, 41±4% for MCF 30% to 41%, and 40±4% for MCF<30% ( P <0.001). After comprehensive adjustment, mortality risk remained high for MCF 30% to 41% (adjusted hazard ratio, 1.53 [1.08-2.18]) and for MCF<30% (adjusted hazard ratio, 1.82 [1.24-2.66]) versus MCF>41%. The optimal MCF cutoff point for mortality prediction was 41%. Age, body mass index, Charlson index, peak aortic velocity, and ejection fraction were independently associated with mortality. MCF (χ 2 to improve 10.39; P =0.001), provided greater additional prognostic value over the baseline parameters than stroke volume (SV) index (χ 2 to improve 5.41; P =0.042), left ventricular mass index (χ 2 to improve 2.15; P =0.137), or global longitudinal strain (χ 2 to improve 3.67; P =0.061). MCF outperformed ejection fraction for mortality prediction. When patients were classified by SV index and MCF, mortality risk was low when SV index was ≥30 mL/m 2 and MCF>41%, higher for patients with SV index ≥30 mL/m 2 and MCF≤41% (adjusted hazard ratio, 1.47 [1.05-2.07]) and extremely high for patients with SV index <30 mL/m 2 (adjusted hazard ratio, 2.29 [1.45-3.62])., Conclusions: MCF is a valuable marker of risk in low-gradient severe aortic stenosis with preserved ejection fraction and could improve decision-making, especially in normal-flow low-gradient severe aortic stenosis with preserved ejection fraction.

Objective: To describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery., Patients and Methods: Between 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months., Results: In the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed., Conclusion: This regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Cardiac output (CO) is routinely assessed by pulsed-wave Doppler echocardiography, yet reference values in adults are lacking. We aim to establish normative values of CO and cardiac index (CI) by pulsed-wave Doppler-echocardiography and to analyze their relation with gender and age in nonobese and obese adults. We included 4,040 adults (mean age: 55 years, 53% women, 950 obese [body mass index ≥30 kg/m²]) with normal blood pressure, no history of cardiovascular disease, and normal transthoracic echocardiography. Normative reference CO and CI values for were calculated in 3,090 nonobese patients by quantile regression. CO normal limits were lower in females than in males (lower limit: 3.3 vs 3.5 L/min, upper limit: 7.3 vs 8.2 L/min). CI normal limits were identical for both genders (lower limit: 1.9 L/min/m², upper limit: 4.3 L/min/m²). Although the relation of CO to age was weak and observed only in women, CI of both genders was not influenced by age. CO of obese patients was significantly greater than that of their nonobese counterparts. CI of obese patients was not influenced by age and gender and was not significantly different than that of nonobese patients (lower limit 1.8 L/min/m², upper limit 4.1 L/min/m² for both genders). In conclusion, in a large adult population we establish normative reference values for CO and CI measured by Doppler-echocardiography. CI is a remarkably stable parameter that is not influenced by age, gender, and body size and should be used to define low- and high-output states., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Most cases of left-sided native valve infective endocarditis (IE) involve a single valve and little is known concerning IE that simultaneously affects the aortic and mitral valves., Methods: We aimed to determine the characteristics, identify the prognostic factors, and define the effect of early surgery for patients with left-sided native bivalvular IE. This analysis included 1340 consecutive patients who presented with definite acute left-sided native valve IE in a 2-centre cohort study., Results: A bivalvular involvement was present in 257 patients (19%). Patients with bivalvular IE had more embolic events (P = 0.044), congestive heart failure (P = 0.016), vegetations, and perivalvular complications (both P < 0.001) than those with monovalvular IE. Early surgery was more frequent for patients with bivalvular IE (P < 0.001). Thirty-day mortality was higher for patients with bivalvular IE than for those with monovalvular IE (24.5% vs 17.6%; P = 0.008), even after adjustment (odds ratio, 1.86 [95% confidence interval, 1.26-2.73]; P < 0.001). Estimated 10-year survival was 70% ± 1% for monovalvular IE and 59% ± 3% for bivalvular IE (P = 0.002). Bivalvular IE was still associated with mortality in multivariable Cox analysis, after adjustment for covariates including age, neurological events, congestive heart failure, Staphylococcus spp infection, perivalvular complications, and early surgery (hazard ratio, 1.70 [95% confidence interval, 1.31-2.11]; P < 0.001). Early surgery was associated with increased survival for patients with bivalvular IE (79% ± 4% vs 35% ± 6%; P < 0.001)., Conclusions: Bivalvular involvement is frequent in left-sided native valve IE, is associated with more embolic events and congestive heart failure than monovalvular IE, and patients are at a high risk of death. Early surgery is associated with improved survival and should be systematically discussed in the absence of contraindication., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background Although women represent half of the population burden of aortic stenosis (AS), little is known whether sex affects the presentation, management, and outcome of patients with AS. Methods and Results In a cohort of 2429 patients with severe AS (49.5% women) we aimed to evaluate 5-year excess mortality and performance of aortic valve replacement (AVR) stratified by sex. At presentation, women were older ( P <0.001), with less comorbidities ( P =0.030) and more often symptomatic ( P =0.007) than men. Women had smaller aortic valve area ( P <0.001) than men but similar mean transaortic pressure gradient ( P =0.18). The 5-year survival was lower compared with expected survival, especially for women (62±2% versus 71% for women and 69±1% versus 71% for men). Despite longer life expectancy in women than men, women had lower 5-year survival than men (66±2% [expected-75%] versus 68±2% [expected-70%], P <0.001) after matching for age. Overall, 5-year AVR incidence was 79±2% for men versus 70±2% for women ( P <0.001) with male sex being independently associated with more frequent early AVR performance (odds ratio, 1.49; 1.18-1.97). After age matching, women remained more often symptomatic ( P =0.004) but also displayed lower AVR use (64.4% versus 69.1%; P =0.018). Conclusions Women with severe AS are diagnosed at later ages and have more symptoms than men. Despite prevalent symptoms, AVR is less often performed in women and 5-year excess mortality is noted in women versus men, even after age matching. These imbalances should be addressed to ensure that both sexes receive equivalent care for severe AS.

Background The prognostic significance of chronic kidney disease (CKD) in severe aortic stenosis is poorly understood and no studies have yet evaluated the effect of aortic-valve replacement (AVR) versus conservative management on long-term mortality by stage of CKD. Methods and Results We included 4119 patients with severe aortic stenosis. The population was divided into 4 groups according to the baseline estimated glomerular filtration rate: no CKD, mild CKD, moderate CKD, and severe CKD. The 5-year survival rate was 71±1% for patients without CKD, 62±2% for those with mild CKD, 54±3% for those with moderate CKD, and 34±4% for those with severe CKD ( P <0.001). By multivariable analysis, patients with moderate or severe CKD had a significantly higher risk of all-cause (hazard ratio [HR] [95% CI]=1.36 [1.08-1.71]; P =0.009 and HR [95% CI]=2.16 [1.67-2.79]; P <0.001, respectively) and cardiovascular mortality (HR [95% CI]=1.39 [1.03-1.88]; P =0.031 and HR [95% CI]=1.69 [1.18-2.41]; P =0.004, respectively) than patients without CKD. Despite more symptoms, AVR was less frequent in moderate ( P =0.002) and severe CKD ( P <0.001). AVR was associated with a marked reduction in all-cause and cardiovascular mortality versus conservative management for each CKD group (all P <0.001). The joint-test showed no interaction between AVR and CKD stages ( P =0.676) indicating a nondifferentialeffect of AVR across stages of CKD. After propensity matching, AVR was still associated with substantially better survival for each CKD stage relative to conservative management (all P <0.0017). Conclusions In severe aortic stenosis, moderate and severe CKD are associated with increased mortality and decreased referral to AVR. AVR markedly reduces all-cause and cardiovascular mortality, regardless of the CKD stage. Therefore, CKD should not discourage physicians from considering AVR.

Background Risk stratification of patients with low-gradient (LG) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction remains challenging. We sought to evaluate the relationship between the dimensionless index (DI)-the ratio of the left ventricular outflow tract time-velocity integral to that of the aortic valve jet-and mortality in these patients. Methods Seven hundred fifty-five patients with LG severe AS (defined by aortic valve area ≤1 cm 2 or aortic valve area indexed to body surface area ≤0.6 cm 2 /m 2 and mean aortic pressure gradient <40 mm Hg) and preserved left ventricular ejection fraction ≥50% were studied. Flow status was defined according to stroke volume index <35 mL/m 2 (low flow, LF) or ≥35 mL/m 2 (normal flow, NF). Results After adjustment for age, sex, body mass index, Charlson comorbidity index, history of hypertension, history of atrial fibrillation, AS-related symptoms, left ventricular ejection fraction, indexed left ventricular ventricular mass, aortic valve area, and aortic valve replacement as a time-dependent covariate, patients with LG-LF and DI<0.25 exhibited a considerable increased risk of death compared with patients with LG-NF and DI≥0.25 (adjusted hazard ratio, 2.41 [95% CI, 1.61-3.62]; P <0.001), LG-NF and DI<0.25 (adjusted hazard ratio, 1.84 [95% CI, 1.24-2.73]; P =0.003), and LG-LF and D≥0.25 (adjusted hazard ratio, 2.27 [95% CI, 1.42-3.63]; P <0.001). In contrast, patients with LG-LF and DI≥0.25, LG-NF and DI<0.25, and LG-NF and DI≥0.25 had similar outcome. DI<0.25 showed incremental prognostic value in patients with LG-LF severe AS but not in patients with LG-NF severe AS. Conclusions Among patients with LG severe AS and preserved left ventricular ejection fraction, decreased DI<0.25 is a reliable parameter in patients with LF to identify a subgroup of patients at higher risk of death who may derive benefit from aortic valve replacement.

Normal-flow low-gradient severe aortic stenosis (NF-LG-SAS), defined by an aortic valve area (AVA) <1 cm², mean pressure gradient (MPG) <40 mm Hg and indexed stroke volume ≥35 ml/m², is the most prevalent form of low-gradient aortic stenosis (AS) with preserved ejection fraction (PEF). However, the true severity of AS in these patients is controversial. The aim of this Doppler echocardiographic study was to investigate changes over time in the hemodynamic severity of patients with NF-LG-SAS with PEF. We retrospectively identified 96 patients who had 2 Doppler echocardiographic examinations without an intervening event. After a median follow-up of 25 (interquartile range 15 to 52) months, progression was observed, with increased transaortic MPG (from 28 [25 to 33] to 39 [34 to 50] mm Hg; p<0.001), peak aortic jet velocity (from 3.46 [3.20 to 3.64] to 4.01 [3.70 to 4.39] m/s; p<0.001), and decreased AVA (from 0.87 [0.82 to 0.94] to 0.72 [0.62 to 0.81] cm²; p<0.001). Median annual rates of progression were 4.3 (1.7 to 8.1) mm Hg/year, 0.25 (0.08 to 0.44) m/s/year, and -0.05 (-0.10 to -0.02) cm²/year, respectively. There was no significant change in left ventricular ejection fraction over time (p = 0.74). At follow-up, 46 patients (48%) acquired the features of classical high-gradient severe AS (MPG ≥40 mm Hg). This study shows that most patients with NF-LG-SAS with PEF exhibit significant hemodynamic progression of AS severity without EF impairment. These findings suggest that NF-LG-SAS with PEF is an "intermediate" stage between moderate AS and classical high-gradient severe AS requiring close monitoring., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Appropriate normalization methods to scale Doppler-derived stroke volume (SV) to body size in patients with aortic stenosis (AS) are poorly defined and reference values are lacking. We aim to establish reference values of normalized SV in adults, and to compare the prognostic value of SV normalized by different methods in AS patients., Methods: In 2781 normotensive, non-obese adults without cardiovascular disease we defined normal relationships between SV and body size by nonlinear regression. Reference SV values were calculated by quantile regression. We subsequently analyzed by Cox analysis the prognostic performance of ratiometric and allometric normalized SV in 1450 patients with severe AS and preserved LVEF under medical and surgical management., Results: Unlike ratiometric normalization, allometric indexation eliminated the residual relationships between normalized SV and body size. The allometric exponents that adequately described the SV-height (H) and SV-body surface area (BSA) relationships were 1.32, and respectively 0.88. In males, low-flow (LF) reference values were: <28 ml/m 2 , <30 ml/m, <30ml/(m 2 ) 0.88 , and, respectively, <26 ml/m 1.32 , and in females <27 ml/m 2 , <28 ml/m, <29ml/(m 2 ) 0.88 , and, respectively, <24 ml/m 1.32 . In patients with severe AS, SV/H 1.32 was most consistently associated with mortality and showed better prognostic performance than other normalized SV parameters (adjusted hazard ratios: 1.86 for SV/H 1.32 , 1.72 for SV/H, 1.64 for SV/BSA, and 1.61 for SV/BSA 0.88 ). Compared to H-normalization, BSA-normalization markedly overestimated the frequency of LF (3% vs. 9%)., Conclusions: We provide normative reference values and appropriate normalization methods for SV by Doppler-echocardiography. In severe AS, SV/H 1.32 seems the most appropriate indexation method, especially in obese individuals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pulmonary hypertension is an established outcome predictor in patients with aortic stenosis (AS), but the prognostic impact of right ventricular dysfunction has not been well studied., Methods: We included 2181 patients (50.4% men; mean age, 77 years) with aortic valve area <1.3 cm 2 and analyzed the occurrence of all-cause death during follow-up according to tricuspid annular plane systolic excursion (TAPSE) quartiles., Results: Patients in the lowest quartile (TAPSE <17 mm) were at a high risk of death, whereas survival was comparable for the 3 other quartiles. Five-year survival was 55±2% for TAPSE <17 mm, 72±2% for TAPSE of 17 to 20 mm, 71±2% for TAPSE of 20 to 24 mm, and 73±2% for TAPSE >24 mm (overall P <0.001). TAPSE <17 mm was associated with increased mortality after adjustment for established prognostic factors (adjusted hazard ratio [HR], 1.55 [95% CI, 1.21-1.97]) and after further adjustment for aortic valve replacement (AVR; adjusted HR, 1.47 [95% CI, 1.15-1.87]). The excess mortality risk associated with TAPSE <17 mm was noticed in both patients managed initially conservatively (adjusted HR, 1.46 [95% CI, 1.20-1.76]) and patients who underwent early (within 3 months after diagnosis) AVR (adjusted HR, 1.61 [95% CI, 1.03-2.52]). In asymptomatic patients with severe AS and preserved ejection fraction, TAPSE <17 mm was independently predictive of mortality (adjusted HR, 2.14 [95% CI, 1.31-3.51]). Early AVR was associated with similar survival benefit in TAPSE <17 and ≥17 mm (adjusted HR, 0.23 [95% CI, 0.16-0.34] for TAPSE <17 mm, adjusted HR, 0.26 [95% CI, 0.19-0.35] for TAPSE ≥17 mm; P for interaction, 0.97)., Conclusions: Right ventricular dysfunction is an important and independent predictor of mortality in AS. TAPSE <17 mm at the time of AS diagnosis is a marker of poor survival under conservative management and after AVR even in asymptomatic patients with severe AS. AVR was associated with a pronounced reduction in mortality independent of TAPSE suggesting that AVR should be discussed before right ventricular dysfunction occurs in severe AS.

Background: Grading of severe (aortic valve area ≤1 cm 2 ) aortic stenosis with preserved left ventricular ejection fraction is based on a classification depending on flow (normal flow versus low flow) and pressure gradient (low gradient versus high gradient). The aim of the present study was to compare the outcome of patients with normal flow high gradient and low flow high gradient severe aortic stenosis (SAS) with no or minimal symptoms., Methods: This multicenter study enrolled 983 consecutive patients (mean age 75±11 years, 459 women) with asymptomatic or minimally symptomatic HG (mean pressure gradient ≥40 mm Hg) SAS with preserved left ventricular ejection fraction. Low flow was defined by Doppler echocardiography as a stroke volume index <30 mL/m 2 (n=131) or a stroke volume <55 mL (n=136). The end point was all-cause mortality., Results: During a median follow-up period of 48 (45-52) months, 225 patients (23%) died. The 60-month mortality was higher in low flow high gradient SAS compared with normal flow high gradient SAS (36±5% versus 22±2% and 38±5% versus 21±2% for stroke volume index and stroke volume, respectively, both P <0.0001). After adjustment for outcome predictors including aortic valve replacement as time-dependent covariate, low flow high gradient SAS displayed considerable mortality risk during follow up compared with normal flow high gradient SAS (adjusted HR 2.17 [1.51-3.13]; P <0.0001 for stroke volume index <30 mL/m 2 and adjusted HR 1.86 [1.29-2.68]; P =0.001, for stroke volume <55 mL). The prognostic impact of low flow was consistent in subgroups of patients., Conclusions: Asymptomatic or minimally symptomatic patients with low flow high gradient SAS and preserved left ventricular ejection fraction have a considerable increased risk of mortality during follow-up. These patients should be promptly considered for aortic valve replacement.

Background Normal-flow, low-gradient severe aortic stenosis (NF-LG-SAS), defined by aortic valve area <1 cm 2 , mean gradient <40 mm Hg, and indexed stroke volume >35 mL/m 2 , is the most prevalent form of low-gradient aortic stenosis (AS). However, the true severity of AS and the management of NF-LG-SAS are controversial. The aim of this study was to evaluate the outcome of patients with NF-LG-SAS compared with moderate AS (MAS) and with high-gradient severe-AS (HG-SAS). Methods and Results A total of 154 patients with NF-LG-SAS, 366 with MAS (aortic valve area between 1.0 and 1.3 cm 2 ), and 1055 with HG-SAS were included. On multivariate analysis, after adjustment for covariates of prognostic importance, NF-LG-SAS patients did not exhibit an excess risk of mortality compared with MAS patients under medical management (hazard ratio=1.13 [95% CI, 0.82-1.56]; P =0.45) and under medical and surgical management (hazard ratio 1.06 [95% CI, 0.79-1.43]; P =0.70), even after further adjustment for aortic valve replacement (hazard ratio=1.09 [95% CI, 0.81-1.48]; P =0.56). The 6-year cumulative incidence of aortic valve replacement (performed in accordance with guidelines) was comparable between the 2 groups (39±4% for NF-LG-SAS and 35±3% for MAS, P =0.10). After propensity score matching (n=226), NF-LG-SAS and MAS patients also had comparable outcomes under medical ( P =0.41) and under medical and surgical management ( P =0.52). NF-LG-SAS had better outcomes than HG-SAS patients (adjusted hazard ratio 1.84 [95% CI, 1.18-2.88]; P <0.001). Conclusions This study shows that patients with NF-LG-SAS have a comparable outcome to those with MAS when aortic valve replacement is performed during follow-up according to guidelines, mostly at the stage of HG-SAS. Rigorous echocardiographic assessment to rule out measurement errors and close follow-up are essential to detect progression to true severe AS in NF-LG-SAS.

Background Moderate aortic stenosis ( MAS ) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Methods and Results We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared with that of the general population. This study included 508 patients (mean±SD age, 75±11 years) with MAS (aortic valve area between 1 and 1.5 cm 2 ; mean±SD aortic valve area, 1.2±0.15 cm 2 ) and preserved left ventricular ejection fraction. Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics, and 48.3% had dyslipidemia. Each patient with MAS was matched for the average survival (per year) of all patients of the same age and same sex from our region (Somme department, north of France). During follow-up (median 47 months), 113 patients (22.2%) underwent aortic valve replacement for severe AS. The mean±SD time between inclusion and surgery was 37±22 months. During follow-up, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53±2% versus 65%). In multivariate analysis, age (hazard ratio, 1.04 [95% CI, 1.02-1.05]; P<0.001), prior atrial fibrillation (hazard ratio, 1.35 [95% CI, 1.05-1.73]; P=0.019), and Charlson comorbidity index (hazard ratio, 1.11 [95% CI, 1.05-1.18]; P=0.002) were associated with increased mortality. Aortic valve replacement was associated with better survival (hazard ratio, 0.38 [95% CI, 0.27-0.54]; P<0.001). Conclusions The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery during follow-up, and increased mortality compared with the general population mainly related to associated comorbidities. Patients with MAS should, therefore, be managed for their cardiovascular risk factors and comorbidities. They require close follow-up, especially when the aortic valve area is close to 1 cm 2 , as aortic valve replacement performed when patients transition to severe AS and develop indications for surgery during follow-up is associated with better survival.

Background: Left atrial (LA) enlargement has been previously identified as a predictor of mortality in patients with medically managed mitral regurgitation (MR) due to mitral valve prolapse (MVP). No study has specifically assessed the prognostic value of LA size in patients undergoing mitral valve repair (MVRp)., Objective: We aimed to investigate the relationship between LA area and mortality in patients in sinus rhythm (SR) undergoing MVRp for MVP., Methods: We included 305 patients in SR who underwent MVRp for MVP. Median follow-up time was 7.9 years. Patients were divided into 3 groups: LA area ≤25 cm2 (reference group), LA 26-30 cm2, and LA >30 cm2., Results: Compared with patients with an LA area ≤25 cm2, those with an LA area >30 cm2 had a lower 10-year survival (98 ± 2 vs. 86 ± 4%; p = 0.037). In multivariate analysis, after adjustment for established outcome predictors including age, symptoms, EuroSCORE, and left ventricular size and function, LA enlargement >30 cm2 was associated with increased mortality (adjusted HR = 2.20, 95% CI 1.03-4.90; p = 0.042), whereas LA enlargement between 26 and 30 cm2 was not (adjusted HR = 1.37, 95% CI 0.56-3.56; p = 0.52)., Conclusion: LA enlargement is independently predictive of long-term mortality after MVRp in patients in SR with severe MR due to MVP. Our findings suggest that MVRp should be considered before the LA area exceeds 30 cm2., (© 2019 S. Karger AG, Basel.)

Objectives: This study sought to determine the best left ventricular ejection fraction (LVEF) cutoff value to predict long-term mortality in patients with asymptomatic or minimally symptomatic severe aortic stenosis (AS) and LVEF ≥50% under conservative management and after surgical correction of AS., Background: Aortic valve replacement (AVR) is a Class I indication in asymptomatic patients with severe AS and LVEF <50%. However, this is an uncommon situation in asymptomatic severe AS (<1% of patients), usually occurring late in the course of the disease. No data are available concerning the prognostic value of LVEF in asymptomatic or minimally symptomatic AS patients with preserved LVEF (≥50%) in order to identify a LVEF threshold value associated with increased mortality., Methods: This analysis included 1,678 patients with preserved LVEF and no or minimal symptoms, with a diagnosis of severe AS. The population was divided into 3 groups: LVEF <55%, LVEF 55% to 59%, and LVEF ≥60%., Results: Five-year survival rate was 72 ± 2% for patients with LVEF ≥60%, 74 ± 2% for patients with LVEF between 55% and 59%, and 59 ± 4% for patients with LVEF <55% (p < 0.001). Under initially conservative or initially surgical management (surgery within 3 months after baseline echocardiography), patients with LVEF <55% displayed significant excess mortality compared to patients with LVEF≥ 60% (adjusted hazard ratio [HR]: 2.44 [95% confidence interval: 1.51 to 3.94]; p < 0.001 and 2.51 [95% confidence interval: 1.58 to 4.00]; p < 0.001, respectively), whereas patients with LVEF between 55% and 59% had comparable prognosis to those with LVEF ≥60% (p = 0.53 and p = 0.36, respectively). In patients with LVEF <55%, initial conservative management was associated with increased mortality compared to initial surgical management, even after covariate adjustment (adjusted hazard ratio [HR]: 2.70 [95% confidence interval: 1.98 to 3.67]; p < 0.001)., Conclusions: In patients with severe AS, preserved LVEF and no or minimal symptoms at the time of diagnosis, LVEF <55% is a marker of poor outcome, with medical or surgical management suggesting that these patients should be considered for surgery before this stage., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)<35 mL/m2. However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk., Methods and Results: This study included 1450 consecutive patients with severe AS (aortic valve area <1 cm2 and/or <0.6 cm2/m2) and preserved LVEF and 1645 controls with normal echocardiograms. Patients were stratified in three groups: (i) SVi > 35 mL/m2 or SV > 70 mL; (ii) SVi 30-35 mL/m2 or SV 55-70 mL; and (iii) SVi < 30 mL/m2 or SV < 55 mL. Mortality with medical and surgical management was analysed. Five-year survival was low for SVi < 30 mL/m2 and SV < 55 mL compared to the other groups (all P-values <0.001). After adjustment for outcome predictors, including aortic valve replacement, mortality risk was considerable with SVi < 30 mL/m2 vs. >35 mL/m2 [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV < 55 mL vs. >70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m2 vs. >35 mL/m2 [adjusted HR 1.05 (0.78-1.41)], and for SV 55-70 mL vs. >70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m2 and SV < 55 mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS., Conclusion: Low flow defined as SVi < 30 mL/m2 or SV < 55 mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making.

Aims: Pulmonary hypertension (PH) is common in severe symptomatic left-sided valvular disease, particularly in aging populations. Inconsistent results have been reported concerning the association between PH and adverse outcomes after aortic valve replacement for aortic stenosis (AS). We therefore retrospectively investigated the prognostic significance of PH using peak tricuspid regurgitation velocity (TRV), as defined by the current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, in a large cohort of patients with severe AS., Methods and Results: One thousand and nineteen patients (541 men; mean age 74 ± 11 years) with severe AS (aortic valve area (AVA) <1 cm2 and/or indexed AVA <0.6 cm2/m2 of body surface area) and LV ejection fraction ≥50% were included. Patients were divided into three groups according to the level of their peak TRV at the time of enrolment: Group 1 (n = 695, 68%) when TRV was ≤2.8 m/s; Group 2 (n = 212, 21%) when TRV was between 2.9 m/s and 3.4 m/s and Group 3 (n = 112, 11%) when TRV was > 3.4 m/s. Median overall follow-up was 31 [6-182] months. On univariate analysis, overall mortality during follow-up was globally different between groups (P < 0.001). On multivariate analysis, Group 3 (TRV >3.4 m/s) exhibited significant excess mortality after adjustment for covariates of prognostic importance (P = 0.032) and after further adjustment for surgery (P = 0.012), using Group 1 as the reference group. Dividing the whole population into two groups with a 3.4 m/s TRV threshold, overall mortality during follow-up was higher in the PH group [hazard ratio (HR) 1.87; 95% confidence interval [1.37-2.56]; P < 0.001)]. On multivariate analysis, after covariate adjustment, including surgery, Group 3 exhibited major excess mortality (adjusted HR 1.46 [1.10-1.95], P = 0.009)., Conclusion: This study demonstrates the negative impact of pulmonary pressure, as assessed by current ESC/ERS guidelines, on long-term outcome of patients with severe AS, irrespective of functional status, chronic obstructive pulmonary disease, AS severity and surgery. Baseline TRV should therefore be taken into account in the management of severe AS.

Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making., Methods and Results: The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 ± 14 years; 70% males; follow-up 7.8 ± 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 ± 1, 57 ± 4, and 21 ± 10% under medical management and 99 ± 1, 82 ± 2, and 57 ± 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P ≤ 0.002)., Conclusion: The MIDA Score may represent an innovative tool for DMR management, being able to position a given patient within a continuous spectrum of short- and long-term mortality risk, either under medical or surgical management. This innovative prognostic indicator may provide a specific framework for future clinical trials aiming to compare new technologies for DMR treatment in homogeneous risk categories of patients.

Objectives: Four patterns of left ventricular (LV) geometry have been described in aortic stenosis (AS): normal geometry, concentric remodelling (LVCR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). LVCR and CH are independently associated with an increased risk of mortality in patients with medically managed AS. No data are available on the impact of aortic valve replacement (AVR) on the negative prognostic implications of LV remodelling patterns., Methods: This study evaluated the long-term postoperative prognostic value of preoperative LV patterns in a cohort of 779 patients (mean age 73 years) with severe AS and ejection fraction >50% undergoing AVR., Results: Long-term postoperative all-cause and cardiovascular mortality in patients with LVCR (adjusted HR = 0.50 [0.17-1.45], p = 0.202, and 0.45 [0.10-2.15], p = 0.373, respectively), CH (adjusted HR = 0.98 [0.68-1.40], p = 0.915, and 1.25 [0.60-2.40], p = 0.556, respectively), or EH (adjusted HR = 1.02 [0.79-1.32], p = 0.870, and 1.18 [0.70-1.99], p = 0.537, respectively) were comparable to those of patients with normal LV geometry., Conclusions: Despite the negative prognostic impact of LVCR and CH observed in patients with medically managed AS, these LV remodelling patterns are not associated with excess mortality after AVR. Surgery should therefore be discussed in patients with LVCR or CH and severe AS to avoid the risk of increased mortality observed under conservative management., (© 2018 S. Karger AG, Basel.)

Objective: Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management., Methods: In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied., Results: Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p<0.0001). In the ACS population, mortality rate was twice than the population without ACS., Conclusions: ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Left atrium (LA) enlargement is common in patients with aortic stenosis (AS), yet its prognostic implications are unclear. This study investigates the value of left atrial volume (LAV) and LAV normalized to body size for predicting mortality in AS., Methods and Results: We included 1351 patients with AS in sinus rhythm at diagnosis and analyzed the occurrence of all-cause death during follow-up with medical and surgical management. Five parameters of LA enlargement were tested: nonindexed LAV and normalized LAV by ratiometric (LAV/body surface area [BSA] and LAV/height) and allometric (LAV/BSA 1.7 and LAV/height 2.0 ) scaling. For each parameter, patients in the highest quartile were at high risk of death, whereas outcome was better and similar for the other quartiles. Five-year survival was lower for patients with LAV >95 mL and LAV/BSA >50 mL/m 2 compared with those with no or mild LA enlargement (both P <0.001). After adjustment for established outcome predictors, including surgery, high risk of death was observed with LAV >95 mL (adjusted hazard ratio, 1.40 [95% confidence interval, 1.06-1.88]) and LAV/BSA >50 mL/m 2 (adjusted hazard ratio, 1.42 [95% confidence interval, 1.08-1.91]). LAV/BSA and LAV showed good and similar predictive performance, whereas other scaling methods did not show better outcome prediction. In patients with severe AS at baseline, preserved (≥50%) ejection fraction, and no or minimal symptoms, LA enlargement was significantly associated with mortality (adjusted hazard ratio, 1.87 [95% confidence interval, 1.02-3.44] for LAV >95 mL, and adjusted hazard ratio, 1.90 [95% confidence interval, 1.03-3.56] for LAV/BSA >50 mL/m 2 )., Conclusions: LA enlargement is an important predictor of mortality in AS, incrementally to known predictors of outcome. LAV and LAV/BSA have comparable predictive performance and should be assessed in clinical practice for risk stratification., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Left atrial (LA) enlargement is frequent in patients with aortic stenosis (AS), yet its determinants and prognostic implications are poorly understood., Aims: To identify the echocardiographic variables associated with increased LA volume index (LAVI), and test the prognostic value of LAVI in AS., Methods: We prospectively included 715 patients with AS in sinus rhythm at enrolment. Echocardiography was performed at baseline. Median follow-up was 22.0 (9-34) months. Patients were divided into two groups according to the best cut-off for event prediction during follow-up (45mL/m 2 )., Results: Compared with LAVI<45mL/m 2 , patients with LAVI≥45mL/m 2 had a lower stroke volume, cardiac output and left ventricular (LV) ejection fraction, greater LV volumes and mass and higher filling pressures. By linear regression, LAVI was best correlated with E wave mitral velocity (r=0.34), E/A ratio (r=0.34), E/e' ratio (r=0.28), indexed LV mass (r=0.29), systolic pulmonary artery pressure (r=0.34) and LV longitudinal strain (r=-0.28). Multivariable analysis confirmed the independent association of LAVI with age (P<0.001), indexed aortic valve area (P=0.04), indexed LV mass (P<0.001), LV ejection fraction (P=0.007), LV end-diastolic volume (P=0.001), E/A ratio (P<0.001) and E/e' ratio (P<0.001). LAVI≥45mL/m 2 was independently predictive of the combined endpoint of cardiovascular death or hospitalization for heart failure (adjusted hazard ratio 1.69, 95% confidence interval 1.04-2.73)., Conclusion: LA enlargement is correlated with AS severity, but also with variables reflecting LV systolic and diastolic dysfunction. Further studies are needed to investigate the outcome implication of LA enlargement in patients with AS., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Current guidelines consider aortic valve replacement reasonable in asymptomatic patients with very severe aortic stenosis (AS); however, the definition of very severe AS based on peak aortic jet velocity (Vmax) remains unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines. Because ≈20% of patients with severe AS and preserved left ventricular ejection fraction have Vmax in this range, we aimed to assess the relationship between Vmax and mortality and determine the best threshold to define very severe AS., Methods and Results: A total of 1140 patients with severe AS (aortic valve area ≤1 cm 2 , Vmax ≥4 m/s) and preserved left ventricular ejection fraction were included. The population was divided into 4 groups according to Vmax (4-4.49, 4.5-4.99, 5-5.49, and ≥5.5 m/s). After adjustment for covariates (including surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49 m/s and Vmax 4.5 to 4.99 m/s ( P =0.64). Both Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted hazard ratio=1.34 [1.18-1.52]; P <0.001, and 1.28 [1.16-1.41]; P <0.001, respectively). Mortality risk was similar for Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s ( P =0.93). Compared with Vmax <5 m/s, patients with Vmax ≥5 m/s had greater mortality risk (adjusted hazard ratio=1.86 [1.55-2.54]; P <0.001), even in the subgroup of asymptomatic even in the subgroup of asymptomatic patients (adjusted hazard ratio=2.08 [1.25-3.46]; P =0.005)., Conclusions: Our results demonstrate the strong relationship between Vmax and mortality in patients with severe AS and preserved left ventricular ejection fraction irrespective of symptoms. Vmax ≥5 m/s at the time of AS diagnosis identifies patients with very severe AS at high risk of death., (© 2017 American Heart Association, Inc.)

Objectives: To assess the anatomical and functional impact of final kissing balloon inflation (FKBI) after implantation of a dedicated bifurcation stent system., Background: Current evidence suggests clinical benefit of FKBI in patients undergoing bifurcation dilatation using the Tryton side branch stent (Tryton-SBS). We hypothesized that FKBI improves anatomical reconstruction and functional results of bifurcation treated by Tryton-SBS., Methods: An unselected group of patients with complex bifurcation coronary lesions undergoing percutaneous coronary intervention (PCI) with Tryton-SBS underwent paired anatomical assessment with two- and three-dimensional quantitative coronary analysis (2D- and 3D-QCA), and optical coherence tomography (OCT), including 3D reconstruction before and after FKBI. Functional assessment by fractional flow reserve (FFR) was performed in the main branch (MB) and side branch (SB) before and after FKBI., Results: Paired pre- and post-FKBI data were obtained in 10 patients. By OCT imaging, FKBI increased both the SB ostial area (4.93 ± 2.81 vs. 7.43 ± 2.87 mm 2 , P < 0.001) and the SB maximum diameter (3.12 ± 0.98 vs. 3.82 ± 1.10 mm, P = 0.003). These findings were associated with a significant increase in FFR in the SB (0.90 ± 0.05 vs. 0.94 ± 0.03; P = 0.011), with no significant change in the MB (0.91 ± 0.05 vs. 0.92 ± 0.04; P = 0.470)., Conclusions: In patients with complex bifurcation stenosis undergoing PCI with a dedicated bifurcation system, FKBI is associated with improved anatomical and functional results at the SB level, without compromising the result at the MB. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Mean transaortic pressure gradient (MTPG) has never been validated as a predictor of mortality in patients with severe aortic stenosis. We sought to determine the value of MTPG to predict mortality in a large prospective cohort of severe aortic stenosis patients with preserved left ventricular ejection fraction and to investigate the cutoff of 60 mm Hg, proposed in American guidelines., Methods and Results: A total of 1143 patients with severe aortic stenosis defined by aortic valve area ≤1 cm 2 and MTPG ≥40 mm Hg were included. The population was divided into 3 groups according to MTPG: between 40 and 49 mm Hg, between 50 and 59 mm Hg, and ≥60 mm Hg. The end point was all-cause mortality. MTPG was ≥60 mm Hg in 392 patients. Patients with MTPG ≥60 mm Hg had a significantly increase risk of mortality compared with patients with MTPG <60 mm Hg (hazard ratio [HR]=1.62 [1.27-2.05] P <0.001), even for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.56 [1.04-2.34] P =0.032). After adjustment for established outcome predictors, patients with MTPG ≥60 mm Hg had a significantly higher risk of mortality than patients with MTPG <60 mm Hg (HR=1.71 [1.33-2.20] P <0.001), even after adjusting for surgery as a time-dependent variable (HR=1.71 [1.43-2.11] P <0.001). Similar results were observed for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.70 [1.10-2.32] P =0.018 and HR=1.68 [1.20-2.36] P =0.003, respectively)., Conclusions: This study shows the negative prognostic impact of high MTPG (≥60 mm Hg), on long-term outcome of patients with severe aortic stenosis with preserved left ventricular ejection fraction, irrespective of symptoms., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation. However, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative mitral regurgitation with a flail leaflet., Methods: MIDA (Mitral Regurgitation International Database) is a multicenter registry enrolling patients with degenerative mitral regurgitation with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1709) and replacement (n=213) overall, by propensity score matching, and by inverse probability-of-treatment weighting., Results: At baseline, patients undergoing MV repair were younger, had more comorbidities, and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching and inverse probability-of-treatment weighting, the 2 treatments groups were balanced, and absolute standardized differences were usually <10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement in both the entire population (1.3% versus 4.7%; P<0.001) and the propensity-matched population (0.2% versus 4.4%; P<0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement in both the entire population (46% versus 23%; P<0.001) and the matched population (41% versus 24%; P<0.001). Similar superiority of MV repair was obtained in patient subsets on the basis of age, sex, or any stratification criteria (all P<0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications., Conclusions: Among patients with degenerative mitral regurgitation with a flail leaflet referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival, and fewer valve-related complications compared with MV replacement., (© 2016 American Heart Association, Inc.)

Background: Four patterns of left ventricular (LV) geometry (normal, concentric remodelling, concentric hypertrophy and eccentric hypertrophy) have been described in aortic stenosis (AS). Although LV concentric remodelling (LVCR), characterized by normal LV mass despite increased LV wall thickness, is frequently observed in AS, its prognostic implication has been not specifically studied., Aim: We aimed to assess, using echocardiography, the prognostic implication of LVCR in asymptomatic or minimally symptomatic patients with AS., Methods: Overall, 331 patients (mean age 73±13 years; 45% women) with AS (aortic valve area≤1.3cm 2 ) and an ejection fraction >50% were enrolled. The endpoints were mortality with conservative management and mortality with conservative and/or surgical management., Results: Sixty-three (19%) patients died under conservative management (follow-up 29±1 months). The highest risk of mortality under conservative management compared with patients with normal LV geometry was observed for LVCR (adjusted hazard ratio [HR]: 3.53, 95% confidence interval [CI]: 1.19-10.46; P=0.023), followed by concentric LVH (adjusted HR: 2.97, 95% CI: 1.02-8.60; P=0.045). Aortic valve replacement was performed in 96 patients (29%) during the entire follow-up (37±1 months); 72 (22%) patients died. Only LVCR remained independently associated with an increased risk of mortality when surgical management during the entire follow-up was considered (adjusted HR: 2.93, 95% CI: 1.19-7.23; P=0.020)., Conclusions: Among the patterns of LV geometry in AS, LVCR portends the worst outcome. Patients with LVCR and AS have a considerable increased risk of mortality, regardless of clinical management., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

: In this article we provide a very interesting and challenging PCI of unrecognized anomalous left circumflex coronary artery (LCx) arising from right sinus of Valsalva (RSV) after aortic valve replacement (AVR).This case presentation focuses the attention on important criteria for recognition of abnormal LCx coronary artery, that is the most frequent congenital coronary variant. Failure to demonstrate the anomaly can lead to erroneous interpretation of coronary anatomy with fatal complication in case of aortic valve replacement, as a consequence of accidental ligation or compression of the anomalous vessel. This procedure, especially in the presence of a bioprosthesis aortic valve just implanted, constitutes a challenge for the interventional cardiologist and at the same time a question mark regarding the strategy, choice of guiding catheter, guide wire, and type of stent to use.

: In this article, we provide very illustrative images obtained with optical coherence tomography (OCT) of a patient presenting with ST-elevation myocardial infarction and multivessel disease. These patients are referred to the catheterization laboratory without performing any prior noninvasive imaging. This leads very often to diagnostic dilemmas with difficult solutions. Coronary angiography is frequently insufficient or even misleading to guide the interventional cardiologist in the identification and revascularization of the culprit coronary lesion. What makes our case particularly paradigmatic is the fact that without OCT guidance, an erroneous clinical decision-making process would have taken place, leaving untreated the culprit lesion in this patient.

Background: Current guidelines define severe aortic stenosis in patients with aortic valve area normalized to body surface area (AVA/BSA) <0.6 cm 2 /m 2 ; yet, this cutoff has never been validated. Moreover, it is not known whether AVA normalization to other body size indexes allows improved outcome prediction. We aim to test the value of AVA normalized to body size for outcome prediction in asymptomatic aortic stenosis., Methods and Results: We included 289 patients with asymptomatic aortic stenosis, preserved ejection fraction, and AVA<1.3 cm 2 at diagnosis. The outcome measure was the occurrence of aortic valve replacement or all-cause death or during follow-up. AVA was normalized to BSA, height, weight, and body mass index. For each normalized index, patients in the lowest tertile were at high risk of events whereas outcome was similar for the other tertiles. High risk of events was observed with AVA/BSA <0.4 cm 2 /m 2 (adjusted hazard ratio [HR], 3.42 [2.09-5.60]), AVA/height <0.45 cm 2 /m (adjusted HR, 3.99 [2.42-6.60]), AVA/weight <0.01 cm 2 /kg (adjusted HR, 3.37 [2.07-5.49]), and AVA/body mass index <0.029 cm 2 /kg per meter square (adjusted HR, 3.23 [1.99-5.24]). Mortality risk was high with AVA/height <0.45 cm 2 /m (adjusted HR, 2.18 [1.28-3.71]), followed by AVA/BSA <0.40 cm 2 /m 2 (adjusted HR, 1.84 [1.09-3.11]), AVA/weight <0.01 cm 2 /kg (adjusted HR, 1.78 [1.07-2.98]), and AVA/body mass index <0.029 cm 2 /kg per meter square (adjusted HR, 1.75 [1.04-2.93]). AVA/height showed better predictive performance than AVA/BSA with improved reclassification and better discrimination (net reclassification improvement: 0.33 versus 0.28; integrated discrimination improvement: 0.10 versus 0.08; C statistic: 0.67 versus 0.65), whereas AVA/weight and AVA/body mass index showed lower predictive capacity., Conclusions: Among AVA normalization methods, AVA/height <0.45 cm 2 /m followed by AVA/BSA <0.40 cm 2 /m 2 seem as robust parameters for defining high risk in asymptomatic aortic stenosis. The prognostic value of AVA/height deserves future research., (© 2016 American Heart Association, Inc.)

Background: The aim of this study was to evaluate the relationship between aortic valve area (AVA) obtained by Doppler echocardiography and outcome in patients with severe asymptomatic aortic stenosis and to define a specific threshold of AVA for identifying asymptomatic patients at very high risk based on their clinical outcome., Methods and Results: We included 199 patients with asymptomatic severe aortic stenosis (AVA ≤1.0 cm(2)). The risk of events (death or need for aortic valve replacement) increased linearly on the scale of log hazard with decreased AVA (adjusted hazard ratio 1.17; 95% CI 1.06-1.29 per 0.1 cm(2) AVA decrement; P=0.002). Event-free survival at 12, 24, and 48 months was 63±6%, 51±6%, and 34±6%, respectively, for AVA 0.8 to 1 cm(2); 49±6%, 36±6%, and 26±6%, respectively, for AVA 0.6 to 0.8 cm(2); and 33±8%, 20±7%, and 11±5%, respectively, for AVA ≤0.6 cm(2) (Ptrend=0.002). Patients with AVA ≤0.6 cm(2) had a significantly increased risk of events compared with patients with AVA 0.8 to 1 cm(2) (adjusted hazard ratio 2.22; 95% CI 1.41-3.52; P=0.001), whereas patients with AVA 0.6 to 0.8 cm(2) had an increased risk of events compared with those with AVA 0.8 to 1 cm(2), but the difference was not statistically significant (adjusted hazard ratio 1.38; 95% CI 0.93-2.05; P=0.11). After adjustment for covariates and aortic valve replacement as a time-dependent variable, patients with AVA ≤0.6 cm(2) had a significantly greater risk of all-cause mortality than patients with AVA >0.6 cm(2) (hazard ratio 3.39; 95% CI 1.80-6.40; P<0.0001)., Conclusions: Patients with severe asymptomatic aortic stenosis and AVA ≤0.6 cm(2) displayed an important increase in the risk of adverse events during short-term follow-up. Further studies are needed to determine whether elective aortic valve replacement improves outcome in this high-risk subgroup of patients., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objectives: This study sought to assess the impact of a wide range of mean right atrial pressure (Pra) on fractional flow reserve (FFR) measurements., Background: FFR invasively assesses the ischemic potential of coronary stenoses. FFR is calculated as the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) during maximal hyperemia. The Pra is considered to have little impact if it is within normal range, so it is neglected in the formula., Methods: In 1,676 stenoses of 1,235 patients undergoing left-right heart catheterization for ischemic (642 [52%]) or valvular heart disease (593 [48%]), the authors compared the FFR values calculated without accounting for Pra (FFR= Pd/Pa) to the corresponding myocardial fractional flow reserve (FFRmyo) values accounting for Pra (FFRmyo = Pd - Pra/Pa - Pra)., Results: The median Pra was 7 (interquartile range [IQR]: 5 to 10) mm Hg with a maximum of 27 mm Hg. The correlation and agreement between FFR and FFRmyo was excellent (R(2) = 0.987; slope 1.096 ± 0.003). The median FFR (0.85; IQR: 0.78 to 0.91) was slightly but statistically significantly higher than the median FFRmyo (0.83; IQR: 0.76 to 0.90; p < 0.001) with a median difference of 0.01 (IQR: 0.01 to 0.02). Values of FFR above the cutoff of 0.80 provided an FFRmyo ≤0.80 in 110 (9%) stenoses. No FFR value above 0.80 provided an FFRmyo ≤0.75., Conclusions: The difference between FFR and FFRmyo was minimal even in patients with markedly increased Pra. FFR values above the gray zone (i.e., >0.80) did not yield values below the gray zone (i.e., ≤0.75) in any case, which suggests that the impact of right atrial pressure on FFR measurement is indeed negligible., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We studied coronary vasomotion in patients treated with the Mistent(®) absorbable polymer sirolimus-eluting stent (APSES) and in patients implanted with the Endeavor(®) zotarolimus-eluting stent (ZES)., Background: First generation (1st-gen) drug-eluting stents (DES) induce persistent vasomotor dysfunction in the treated coronary artery. It is unknown whether and to what extent the implantation of an absorbable polymer DES impairs coronary vasomotion., Methods: This sub-study of the DESSOLVE II trial included 19 APSES Mistent(®) and 10 ZES Endeavor(®) patients. Incremental atrial pacing and quantitative coronary angiography were used to assess vasomotion proximal and distal to the stent and in a reference segment at 9 months after implantation. Percent changes in vessel diameter with pacing versus baseline were calculated and compared. Vasomotor response of the APSES group was also compared with changes observed in a historical group of 17 patients implanted with a 1st-gen sirolimus-eluting stent (SES)., Results: Normal vasomotion (vasodilatation) was preserved and of comparable magnitude in the APSES and in the ZES group both proximally (P = 0.34) and distally (P = 0.38) to the stent. This finding was not observed in the 1st-gen SES group showing marked pacing-induced vasoconstriction at both stent edges (P < 0.05 vs. APSES). The results were practically unchanged after excluding patients with absolute changes in vessel diameter <3% between baseline and maximal pacing., Conclusions: The implantation of an absorbable polymer sirolimus-eluting stent is associated with preserved coronary vasomotion, comparable to that observed after implantation of the Endeavor(®) ZES, and distinct from 1st-gen SES which induce coronary vasomotor dysfunction., (© 2015 Wiley Periodicals, Inc.)

Atrial fibrillation (AF) is frequently encountered in patients with aortic stenosis (AS) and its incidence also increases with age. In the general population, AF is known to increase cardiovascular risk. We sought to investigate the prognostic importance of AF associated with AS in the context of routine clinical practice. This analysis was based on 809 patients (75 ± 12 years) diagnosed with AS (aortic valve area <2 cm(2)) and normal (≥50%) ejection fraction (EF). Patients were grouped according to the presence of sinus rhythm (SR) or AF at study enrollment. The AF group comprised 141 patients (17.5%) with AF, whereas 668 patients (82.5%) were in SR at inclusion. Four-year estimates of all-cause mortality with medical and surgical management were 60 ± 5% for the AF group compared with 24 ± 2% for the SR group (p = 0.0001). On multivariate analysis, the risk of all-cause mortality was higher in the AF group than in the SR group (adjusted hazard ratio [HR] 2.47 [1.83 to 3.33], p = 0.0001). AF remained associated with excess mortality risk when the analysis was limited to asymptomatic patients (adjusted HR 2.31 [1.38 to 3.89], p = 0.002) and, respectively, patients with severe AS (adjusted HR 2.22 [1.41 to 3.49], p = 0.001). Among patients managed medically, AF was independently associated with increased risk of death in the overall study population (adjusted HR 2.52 [1.81 to 3.51], p = 0.0001), in asymptomatic AS (adjusted HR 2.12 [1.19 to 3.76], p = 0.01), and in severe AS (adjusted HR 2.23 [1.30 to 3.81], p = 0.004). In conclusion, AF is a major predictor of mortality, in both medically and surgically managed patients with AS, irrespective of the functional status and the severity. AF is, therefore, a strong marker of risk in AS and should be considered for clinical decision making., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Low-gradient (LG), low-flow (LF), severe aortic stenosis (AS) with preserved ejection fraction (PEF) is considered by some authors as an advanced form of AS associated with very poor outcome. The aim of this Doppler echocardiographic study was to investigate changes over time in the hemodynamic severity of LG/LF AS with PEF. We retrospectively identified in 2 academic centers 59 patients who had 2 Doppler echocardiographic examinations without an intervening event. After a median follow-up of 2 (interquartile range [IQR] 1.3 to 3.5) years, progression was observed with increase in mean Doppler gradient (MDG; from 27 [23 to 32] to 37 [28 to 44] mm Hg; p <0.001), peak aortic jet velocity (from 330 [314 to 366] to 373 [344 to 423] cm/s; p <0.001), and decrease in aortic valve area (AVA; from 0.73 [0.63 to 0.92] to 0.64 [0.56 to 0.75] cm(2); p = 0.001). Annual rates were, respectively, 8 mm Hg/year, 36 cm/s/year, and -0.04 cm(2)/year. EF decreased from 62% (55% to 69%) to 58% (51% to 65%), p = 0.001. At follow-up, MDG increase was observed in 51 patients (86%), and 24 patients (41%) acquired the features of classical high-gradient (HG) severe AS (MDG ≥40 mm Hg and peak aortic jet velocity ≥400 cm/s). There were no differences as regard to baseline hemodynamic parameters between patients who displayed ≥5 mm Hg MDG increase and those in whom such increase was not observed. In conclusion, most patients with LG/LF AS with PEF exhibit over time increase in MDG and decrease in AVA with slight EF impairment. This result suggests that LG/LF AS with PEF is an intermediate stage between moderate AS and HG AS rather than an advanced form of the disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the role of the dimensionless index (DI) in a registry of patients with aortic stenosis (AS) to objectively establish prognostic DI thresholds for various degrees of AS severity., Background: DI is a classic marker of severity in AS that does not rely on the estimation of the left ventricular outflow tract (LVOT) cross-sectional area. Although DI estimation is straightforward, its outcome implications have never been tested in the context of routine clinical practice., Methods: This analysis includes 488 patients with preserved (≥50%) ejection fraction and no or minimal subjective symptoms, diagnosed with ≥ mild AS. DI was computed as the ratio of the LVOT time-velocity integral to that of the aortic valve jet, and on the basis of the correlation with peak aortic jet velocity, the population was divided into 3 groups: DI <0.20, DI 0.20 to 0.25, and DI >0.25., Results: The 5-year survival free of events (death or need for aortic valve replacement) was 56 ± 3% for DI >0.25, 41 ± 6% for DI 0.20 to 0.25, and 22 ± 5% for DI <0.20 (p for trend <0.001). The risk of events increased linearly with DI <0.25 (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.05 to 1.29) per 0.05 DI decrement; p = 0.015). On multivariable analysis, compared with patients with DI >0.25, those with DI 0.20 to 0.25 and those with DI <0.20 incurred an excess risk of events (adjusted HR: 1.65; 95% CI: 1.20 to 2.27 for DI 0.20 to 0.25 vs. DI >0.25, and adjusted HR: 2.62; 95% CI: 1.90 to 3.63 for DI <0.20 vs. DI >0.25). The association of DI and outcome was consistent in subgroups, with no interaction between DI outcome prediction and LVOT diameter, body surface area, or index stroke volume (all p for interaction ≥0.10) CONCLUSIONS: Our results demonstrate that the DI is a simple and reliable marker of AS severity with clear prognostic implications. DI <0.25 is associated with an excess risk of events after diagnosis; therefore, this cutoff should be used for AS severity assessment and for therapeutic decisions., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to assess the impact of atrial fibrillation (AF) on outcome in patients who underwent mitral valve repair (MVRp) for mitral valve prolapse (MVP). Four hundred and forty-three consecutive patients underwent MVRp for organic mitral regurgitation due to MVP. Echocardiography was performed preoperatively and after surgery. Postoperative left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF) <50%. Before surgery, 187 patients (42%) had preoperative AF. After surgery, LVEF significantly decreased from 67 ± 9% to 56 ± 10% (p <0.0001). Compared with patients in sinus rhythm (SR), those in AF were significantly older (p <0.0001), had more severe symptoms (p = 0.004), had lower LVEF (p = 0.002), and higher EuroSCORE (p = 0.05). Compared with patients in SR, patients with AF had significantly lower 10-year survival (64 ± 4% vs 83 ± 3%, p = 0.001). On multivariate analysis, preoperative AF was identified as an independent predictor of overall mortality (hazard ratio 1.67; 95% confidence interval 1.15 to 2.42; p = 0.007). At 10 years, patients with paroxysmal AF had lower survival and higher heart failure rate than patients in SR (78 ± 3% vs 66 ± 6%) but had a better outcome compared with those with permanent AF (66 ± 6% vs 53 ± 6%, p = 0.022). Patients with AF had a significantly higher rate of postoperative LVD (23.3% vs 13.4%, p = 0.007). In conclusion, preoperative AF is a predictor of long-term mortality and postoperative LVD after MVRp for MVP. To improve postoperative outcome, surgery in these patients should be performed before onset of AF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD., Methods and Results: This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001)., Conclusions: FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)