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BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; PCONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Cardiac involvement in systemic light chain (AL) amyloidosis carries a poor prognosis mainly through involvement of the left ventricular (LV) myocardium. Despite its limitations, two-dimensional transthoracic echocardiography (2D-TTE) remains the main tool used for the assessment of LV systolic function in AL patients. We hypothesize that 3D-TTE coupled with speckle tracking imaging allows earlier detection of LV systolic dysfunction than 2D-TTE in AL amyloidosis. We prospectively studied 71 subjects including 58 patients with confirmed AL amyloidosis (mean age 66 +/- 10years, 60% male) and 21 healthy control (mean age 64 +/- 7years, 48% male) from 2011 to 2014at the University Hospital of Limoges. The AL patients were divided into three groups according to Mayo Clinic (MC) staging and all subjects underwent 2D-TTE and 3D-TTE at the same setting. Using 2D-TTE, there was no significant difference in LV ejection fraction (EF) between the groups [LVEF=63 +/- 7% (control), 59 +/- 6% (MC stage I), 60 +/- 8% (MC stage II) and 57 +/- 14% (MC stage III) (p=0.24)]. In contrast, 3D-TTE demonstrated significantly worse LV systolic function in stage II and III patients using 3D-LVEF [MC II and III 45 +/- 8% and 39 +/- 12% vs. control 53 +/- 8% (p

Background Aortic stenosis (AS) is the most common valvular disease. Nowadays, the degenerative process including valve calcification is the main etiology. Severe AS is associated with poor prognosis and is an indication for aortic-valve intervention. While echocardiography is the main imaging tool to diagnose and quantify AS severity, computed tomography can also be used in difficult cases, and the aortic-valve calcification score is proposed as a proxy to quantify the disease severity. Nevertheless, different thresholds are proposed to grade AS. We performed systematic review and meta-analysis of studies using computed tomography to diagnose severe AS. Method Up to 30/11/2018, the key terms “aortic-valve”, “stenosis”, “computed tomography”, “calcification” or “calcium” were searched in PubMed. Our predefined inclusion criteria were clinical studies to diagnose severe AS by aortic-valve calcification derived from computed tomography. Studies including only native valves and providing cut-off levels for stenosis severity were included. The Agatston method were used and expressed in Agatston unit. Results Eleven from 534 studies, including 4,529 patients, were eligible. Population, AS severity, acquisition modalities and results were heterogenous. Aortic-valve calcification score was accurate to diagnose severe AS (pooled area under the curve = 0.89 ± 0.02). The cut-off levels differed between studies. With meta-analysis, the optimal cut-off was 1,648 AU for general population. Only three studies provided a cut-off per gender, with optimal value derived from meta-analysis of 1,354 AU for women and 2,048 AU for men. Conclusion Aortic-valve calcification score derived from computed tomography is useful to diagnose severe AS. It can provide supplementary data for evaluation of AS in patients with discordant echocardiographic findings. However, individual participant data meta-analysis is required to identify the most appropriate cut-off values with better accuracy.

BACKGROUND: Fabry cardiomyopathy (FC) and light-chain amyloid cardiomyopathy (AL) present with concentric left ventricular (LV) hypertrophy/remodeling and diastolic rather than systolic dysfunction. Direct comparisons are difficult due to rarity and confounded by variability of LV thickness. AIMS: To compare LV diastolic and systolic properties between patients with FC and AL in a cohort matched for interventricular septal thickness (IVS). METHODS: A two-center echocardiographic analysis was performed, comprising 118 patients with IVS ≥12 mm (FC and AL 59 patients each) matched by IVS. RESULTS: Fabry cardiomyopathy patients had larger LV end-diastolic diameter (47.7 [44.0-50.9] vs 45.0 [41.5-49.0] mm, P = 0.002), better LV ejection fraction (EF 68.7 [63.4-74.0] vs 63.0 [54.0-70.0]%, P = 0.001) and midwall fractional shortening (midFS 14.8 [13.0-16.1] vs 12.1 [8.9-15.0]%, P = 0.006). LV EF

Background: Systemic light chain amyloidosis (AL) is characterized by the extracellular deposition of amyloid fibrils. Transthoracic echocardiography is the modality of choice to assess cardiac function in patients with AL. Whereas left ventricular (LV) function has been well studied in this patient population, data regarding the value of left atrial (LA) function in AL patients are lacking. In this study, we aim to examine the impact of LA volumes and function on survival in AL patients as assessed by real-time 3D echocardiography. Methods: A total of 77 patients (67 ± 10 years, 60% men) with confirmed AL and 39 healthy controls were included. All standard 2D echocardiographic and 3D-LA parameters were obtained. Results: Fourteen patients (18%) were in Mayo Clinic (MC) stage I, 30 (39%) in stage II, and 33 (43%) in stage III at initial evaluation. There was no significant difference among the MC stages groups in terms of age, gender, or cardiovascular risk factors. As compared to patients in MC II and MC I, those in MC III had significantly larger indexed 3D-LA volumes (MCIII: 46 ± 15 mL/m 2, MC II: 38 ± 12 mL/m 2, and MC I: 23 ± 9 mL/m 2, p < 0.0001), lower 3D-LA total emptying fraction (3D-tLAEF) (21 ± 13% vs. 31 ± 15% vs. 43 ± 7%, respectively, p < 0.0001), and worse 3D peak atrial longitudinal strain (3D-PALS) (11 ± 9% vs. 18 ± 13% vs. 20 ± 7%, respectively, p = 0.007). Two-year survival was significantly lower in patients with 3D-tLAEF < + 34% (p = 0.003) and in those with 3D-PALS < + 14% (p = 0.034). Both parameters provided incremental prognostic value over maximal LA volume in multivariate analysis. Conclusion: Functional LA parameters are progressively altered in AL patients according to the MC stage. A decrease in 3D-PALS is associated with worse outcome, independently of LA volume.

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Introduction: Global left ventricular (LV) afterload as assessed by valvulo-arterial impedance (Zva), may be an independent predictor of mortality in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (LVEF). However, its quantification using echocardiography may be subject to error measurement. We aimed to determine the prevalence and impact on long-term survival of high Zva, purposely measured by cardiac catheterization. Methods and results: 676 patients with preserved LVEF and severe AS without other valvular heart diseases underwent cardiac catheterization. Zva was derived from catheterization and calculated as follows: mean aortic gradient + systolic blood pressure/ indexed LV stroke volume. Zva was considered high when > 5mmHg/mL/m(2) based on previous studies. Overall, high Zva was found in 42% of all AS patients. Four-year survival and 8-year survival were significantly reduced in patients with high Zva (74 +/- 3% and 57 +/- 4%) as compared to those with low Zva (85 +/- 2% and 74 +/- 3%; p = 0.002). After adjustment for all other risk factors, Zva was independently associated with reduced long-term survival (hazard ratio [HR] = 1.47 95% CI: 1.04-2.09; p = 0.029). Of interest, high Zva remained associated with reduced survival as compared to low Zva, in patients with normal LV stroke volume, but was no longer significant in low flow patients (p = 0.98). Conclusion: High Zva, estimated invasively in our study, is frequent in patients with severe AS, and appears as a robust and independent predictor of survival. Zva should be used as an additional parameter for risk stratification of severe AS, more particularly in patients with normal flow. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

International audience; AIMS:The prognostic impact of elevated pulmonary arterial pressure (PAP) remains controversial in aortic stenosis (AS) and few studies focused on patients with preserved left ventricular ejection fraction (LVEF). We aimed to investigate the impact of pulmonary hypertension (PH), invasively derived, on survival in severe AS with preserved LVEF.METHODS AND RESULTS:Between 2000 and 2010, 749 patients (74 ± 8 years, 57% males) with preserved LVEF and severe AS without other valvular heart disease underwent cardiac catheterization. PH was defined as mean PAP > 25 mmHg. The mean follow-up was 4.6 ± 3.0 years. Overall, 32% (n = 241) of patients had PH. Surgical aortic valve replacement (SAVR) was performed in 91% of patients with 4.5% of 30-day mortality rate, significantly higher in patients with PH than without PH (7.5 vs. 3.5%, p = 0.014). In logistic regression, PH was an independent predictor of increased 30-day mortality (odds-ratio = 2.2, p = 0.04). Overall long-term survival was significantly reduced in patients with PH as compared to those without (10-year: 52 ± 5 vs. 68 ± 3%, p

International audience; BACKGROUND:Left heart valve thickening (LVT) was described in patients with light-chain amyloidosis (AL). This phenomenon reflects likely infiltration of the valve by amyloid proteins. However, the prevalence of LVT and its prognostic value have not been investigated in patients with AL.METHODS AND RESULTS:Comprehensive transthoracic echocardiography was performed at baseline in 150 patients [median age 68 (33-87) years; 59% male] with confirmed AL. The presence of abnormal mitral and/or aortic valve thickening (>3 mm) was assessed in all included patients. Overall, 42% had LVT at the time of diagnosis. Compared to patients without LVT, those with LVT were older and had a more advanced NYHA functional class (63% in patients with NYHA III-IV vs. 33% in NYHA I-II, p < 0.001). They also had higher left ventricular (LV) wall thickness and mass, larger left atrium, higher mitral annulus E/E' ratio and systolic pulmonary artery pressures, and lower LV ejection fraction (all p < 0.05). Patients with more advanced Mayo Clinic stage had a higher incidence of LVT: 58% in stage III vs. 45% in stage II and 5% in stage I (p < 0.001). During a median follow-up of 2 years, 79 deaths occurred. The presence of LVT was significantly associated with reduced 5-year survival (32 ± 7 vs. 64 ± 6%). In multivariate analysis, after adjusting for age, gender, NYHA functional class, and LV ejection fraction, LVT remained significantly associated with higher all-cause mortality (hazard ratio 1.90, 95% CI 1.10-3.34, p = 0.02).CONCLUSION:Left heart valve thickening is common in patients with AL and is associated with worse functional class, LV systolic and diastolic function, and more advanced stage of the disease. In addition, LVT appears to be a powerful marker of all-cause mortality.

Background Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. Methods and results Fifty-four consecutive patients (age 66 +/- 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 +/- 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 +/- 15 vs. 46 +/- 13 vs. 52 +/- 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 +/- 6 vs. 34 +/- 11 vs. 44 +/- 17 mL/m2, P < 0.001), lower LAEF (42 +/- 9 vs. 26 +/- 13 vs. 16 +/- 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA >= II, 22 +/- 14%) as compared with asymptomatic patients (NYHA class I, 33 +/- 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF 16% (37 +/- 11 vs. 94 +/- 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease, 95%CI: 1.02-1.15, P = 0.003). Conclusion In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality.

Background Cardiac involvement in systemic light-chain amyloidosis (AL) is characterized by 2D-echocardiography (TTE) normal or slithly decreased left ventricular (LV) ejection fraction and typically a diastolic dys-function with left atrial (LA) enlargement. To assess cardiac involvement, the Mayo Clinic staging (MC) using NTproBNP and troponin, has been validated and allows risk stratification of patients into 3 groups with different outcomes. Cardiac magnetic resonance (CMR) assesses accurately chambers size and function. We aimed to compare by TTE and by CMR respectively: features of LV systolic and diastolic function and by CMR, morphological functional parameters namely LV myocardial late gadolinium enhancement (LGE) and indexed max LA volume (LAVi) and emptying fraction (LAEF). Methods and results Forty-two consecutive patients (66±10 years, 57% males) in sinus rhythm with confirmed systemic AL, underwent simultaneously TTE and CMR within 24 hours. LAEF was calculated after assessing the maximal and minimal LAVi (by area/length formula) in CMR using 4 and 2 chambers views. Diastolic parameters and 2D-LV global longitudinal strain (GLS) obtained by TTE were stratified according to LAEF, to LAVi and to the presence or not of LGE. Patients in MC stage III had the worse TTE and CMR parameters. LV GLS (–10.1±3.1 vs. –17.3±3.7, p Conclusion In systemic AL, reduced LV GLS is associated with presence of LGE while impaired LV filling pressures are rather related to decreased LA emptying fraction. Multimodality imaging in patients with AL may allow better and complementary assessment of LV hemodynamics. Abstract 0430 - Table LA Emptying fraction CMR Maximal LAVICMR LGE >17.5% p >44 ml/m2 p – + p Mitral E/A ratio 2.98±1.82 0.89±0.28 1.51±1.4 2.22±1.8 0.2 1.35±1.3 2.43±1.9 0.055 DT TTE (ms) 158±45 217±56 190±65 183±53 0.7 219±51 145 ±39 Lateral E/e’ 16.9±6.8 12.1±6.4 14±7 14.8±7 0.8 13.6±7.4 15.7±6.4 0.4 GLS –10.1±3.1 –17.3±3.7 –14.2±5 –12.7±4.6 0.4 –16.5±5.2 –10.8±2.8

International audience; AIMS:Previous studies using echocardiography suggested that a low flow (LF) defined as an indexed stroke volume (SVi) 50%) and severe AS (valve area ≤1 cm(2)) without other valvular heart disease underwent cardiac catheterisation. The long-term overall mortality was assessed as the primary end-point.RESULTS:Mean age was 74±8 years, 58% were men, 46% had coronary artery disease and mean LVEF was 72±10%. Low SVi was found in 27% (n=210) of patients with AS. As compared with patients with normal SVi, those with low SVi were significantly older (p

Background— Patients with severe aortic stenosis (AS) and paradoxical low flow (PLF) have worse outcome compared with those with normal flow. Furthermore, prosthesis–patient mismatch (PPM) after aortic valve replacement is a predictor of reduced survival. However, the prevalence and prognostic impact of PPM in patients with PLF-AS are unknown. We aimed to analyze the prevalence and long-term survival of PPM in patients with PLF-AS. Methods and Results— Between 2000 and 2010, 677 patients with severe AS, preserved left ventricular ejection fraction, and aortic valve replacement were included (74±8 years; 42% women; aortic valve area, 0.69±0.16 cm 2 ). A PLF (indexed stroke volume ≤35 mL/m 2 ) was found in 26%, and after aortic valve replacement, 54% of patients had PPM, defined as an indexed effective orifice area ≤0.85 cm 2 /m 2 . The combined presence of PLF and PPM was found in 15%. Compared with patients with noPLF/noPPM, those with PLF/PPM were significantly older, with more comorbidities. They also received smaller and biological bioprosthesis more often (all P P =0.002), even after multivariable adjustment (hazard ratio, 2.58; 95% confidence interval, 1.5–4.45; P =0.0007). Conclusions— In this large catheterization-based study, the coexistence of PLF-AS before surgery and PPM after surgery is associated with the poorest outcome.

IntroductionThe non-invasive assessment of left ventricular (LV) filling and LA pressure in patients with aortic stenosis (AS) remains challenging. The aim of our study was to identify the echocardiographic parameters that may predict elevated pulmonary capillary wedge pressures (PCWP) measured by cardiac catheterization in patients with severe AS without other valve disease.Methods and resultsFrom January 2010 to December 2012, we included 85 consecutive patients with severe AS scheduled for clinically indicated cardiac catheterization study. Comprehensive transthoracic echocardiography (TTE) was performed in all patients within 24 hours of the hemodynamic study. Mean age was 75±9 years, 65% of them were male, 65%, 22% and 54% had respectively a history of hypertension, diabetes, and dyslipidemia. NYHA functional class was≥III in 63% of patients. By TTE, mean LV ejection fraction, max left atrial (LA) volume indexed, were respectively 60±9%, and 38±16mL/m 2. Mean mitral septal E/e’ ratio was 18.6±9. Cardiac catheterization found 60% cases of coronary artery disease and the mean PCWP was 13.5±7mmHg. As compared to patients with low PCWP (29ml/m 2 predicted a PCWP>13mmhg with a sensitivity of 77% and a specificity of 62% (area under the curve=0.73). Similarly, mitral annular septal E/e’>12 predicted PCP>13mmHg with a sensitivity of 90% and a specificity of 60% (area under the curve=0.73).ConclusionIn severe AS patients, maximal LA indexed volume>29/ml/m2 and E/e’ ratio>12, derived from TTE, appear as good markers of elevated PCWP. Further studies are needed to investigate their prognostic values.

BackgroundThe global left ventricular (LV) hemodynamic afterload as assessed by valvulo arterial impedance (Zva), may be an independent predictor of mortality in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (LVEF). However, its quantification using echocardiography may be subject to error measurement. The aim of this study is to determine the prevalence and impact on long-term survival of high Zva, purposely measured by cardiac catheterization.Methods and results768 patients with preserved LVEF (>50%) and severe AS (valve area ≤1cm²) underwent cardiac catheterization. Zva was derived from catheterization data and calculated using validated formula. Zva was considered high when >5mmHg/ml/m2. Overall, high Zva was found in 42% of all AS patients.Patients with high Zva were significantly older (p60mL: 49±8vs. 69±4%, p=0.012; ≤60mL: 49±7 vs. 53±13%, p=0.96).ConclusionIn this large cardiac catheterization-based study, high Zva estimated invasively is frequent in patients with severe AS, and appears as a robust and independent predictor of survival.

Background Cardiac involvement in systemic light-chain amyloidosis (AL) is characterized by slightly decreased systolic left ventricular function (LV) function and typically a diastolic dysfunction including left atrial (LA) enlargement. Cardiac magnetic resonance (CMR) is often performed in AL to accurately assess chambers size and function. We aimed to compare features of LV systolic and diastolic function obtained by 2D transthoracic echocardiography (TTE), with morphological and functional myocardial LV (presence of late gadolinium enhancement: LGE) and LA (volume and emptying fraction) parameters as assessed by CMR in a consecutive series of patients with cardiac AL.

BackgroundThe prognostic impact of pulmonary arterial pressure (PAP) remains controversial in aortic stenosis (AS) and few studies focused only on patients with preserved left ventricular ejection fraction (LVEF). We therefore aimed to investigate the impact of PAP, derived from our large catheterization database, on survival in severe AS with preserved LVEF.Methods and resultsBetween 2000 and 2010, 749 patients (74±8y, 57% of males) with preserved LVEF and severe AS without other valvular heart disease underwent cardiac catheterization, including right heart hemodynamic assessment. Pulmonary hypertension (PH) was defined as mean PAP>25mmHg.Systolic and mean PAP were 34.5±12 and 21.9±9mmHg, respectively. Overall, 29% (n=215) of patients had PH, and these patients were significantly older (p

Previous studies suggested valvulo arterial impedance (Zva) may be an independent predictor of mortality in patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF). However, its quantification using echocardiography may be subject to error measurement. Aim