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Background: Assessing the true severity of aortic stenosis (AS) remains a challenge, particularly when echocardiography yields discordant results. Recent European and American guidelines recommend measuring aortic valve calcium (AVC) by multidetector row computed tomography (MDCT) to improve this assessment.Aim: To define, using a standardized MDCT scanning protocol, the optimal AVC load criteria for truly severe AS in patients with concordant echocardiographic findings, to establish the ability of these criteria to predict clinical outcomes, and to investigate their ability to delineate truly severe AS in patients with discordant echocardiographic AS grading.Methods and Results: Two hundred and sixty-six patients with moderate-to-severe AS and normal LVEF prospectively underwent MDCT and Doppler-echocardiography to assess AS severity. In patients with concordant AS grading, ROC analysis identified optimal cut-off values for diagnosing severe AS using different AVC load criteria. In these patients, 4-year event-free survival was better with low AVC load (60–63%) by these criteria than with high AVC load (23–26%, log rank p < 0.001). Patients with discordant AS grading had higher AVC load than those with moderate AS but lower AVC load than those with severe high-gradient AS. Between 36 and 55% of patients with severe LG-AS met AVC load criteria for severe AS. Although AVC load predicted outcome in these patients as well, its prognostic impact was less than in patients with concordant AS grading.Conclusions: Assessment of AVC load accurately identifies truly severe AS and provides powerful prognostic information. Our data further indicate that patients with discordant AS grading consist in a heterogenous group, as evidenced by their large range of AVC load. MDCT allows to differentiate between truly severe and pseudo-severe AS in this population as well, although the prognostic implications thereof are less pronounced than in patients with concordant AS grading.

BACKGROUND: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. OBJECTIVES: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. METHODS: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. RESULTS: Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values

To evaluate left ventricular (LV) reverse remodeling after repair surgery for mitral regurgitation (MR) or aortic regurgitation (AR), aiming at determining optimal preoperative thresholds for normalization of LV volumes and function after surgery. Observational prospective cohort study. Single-center, academic, tertiary care cardiovascular center. Patients and volunteers. Cardiac magnetic resonance with measurement of indexed LV end-diastolic volume (LVEDVi) and end-systolic volume (LVESVi), mass (LVmassi), and ejection fraction (LVEF) was performed preoperatively and postoperatively. The authors included 29 patients with AR and 59 patients with MR (46 ± 12 and 56 ± 12 years, follow-up 222 ± 57 days). Both AR and MR repair resulted in a significant reduction of LV volumes and mass (respectively, delta change in LVEDVi -55 mL/m² and -43 mL/m²; in LVESVi -26 mL/m² and -10 mL/m²; and in LVmassi -24 g/m² and -12 g/m²; p < 0.001 for all). Yet despite the absence of perioperative necrosis, 7 (24%) patients with AR had persistent LV dilatation (LVEDVi >106 mL/m²) relative to controls and 16 (27%) patients with MR developed systolic LV dysfunction (LVEF 155 mL/m² for AR and >129 mL/m² for MR. Although both AR and MR repair allow significant reverse postoperative LV remodeling, persistent LV dilatation after AR correction and systolic LV dysfunction after MR repair are common and best predicted by increased preoperative LV volumes. This highlights the importance of considering LV volumes in the decision-making process.

OBJECTIVES: To validate aortic valve calcium (AVC) load measurements by multidetector row computed tomography (MDCT), to evaluate the impact of tube potential and slice thickness on AVC scores, to examine the accuracy of AVC load in distinguishing severe from nonsevere aortic stenosis (AS) and to investigate its effectiveness as an alternative diagnosis method when echocardiography remains inconclusive. METHODS: We prospectively studied 266 consecutive patients with moderate to severe AS who underwent MDCT to measure AVC load and a comprehensive echocardiographic examination to assess AS severity. AVC load was validated against valve weight in 57 patients undergoing aortic valve replacement. The dependence of AVC scores on tube potential and slice thickness was also tested, as well as the relationship between AVC load and echocardiographic criteria of AS severity. RESULTS: MDCT Agatston score correlated well with valve weight (r = 0.82, p < 0.001) and hemodynamic indices of AS severity (all p < 0.001). Ex-vivo Agatston scores decreased significantly with increasing tube potential and slice thickness (repeated measures ANOVA p < 0.001). Multivariate analysis identified mean gradient, the indexed effective orifice area, male gender and left ventricular outflow tract cross-sectional area as independent correlates of the in-vivo AVC load. CONCLUSIONS: MDCT-derived AVC load correlated well with valve weight and hemodynamic indices of AS severity. It also depends on tube potential and slice thickness, thus suggesting that these parameters should be standardized to optimize reproducibility and accuracy.

Studies suggesting that B-type natriuretic peptide (BNP) may predict outcomes of mitral regurgitation (MR) are plagued by small size, inconsistent etiologies, and lack of accounting for shifting normal BNP ranges with age and sex.This study assessed the effect of BNP activation on mortality in a large, multicenter cohort of patients with degenerative MR.In 1,331 patients with degenerative MR, BNP was prospectively measured at diagnosis and expressed as BNPratio (ratio to upper limit of normal for age, sex, and assay). Initial surgical management was performed within 3 months of diagnosis in 561 patents.The cohort had a mean age of 64 ± 15 years, was 66% male, and had a mean ejection fraction 64 ± 9%, mean regurgitant volume 67 ± 31 ml, and low mean Charlson comorbidity index of 1.09 ± 1.76. Median BNPratio was 1.01 (25th and 75th percentiles: 0.42 to 2.36). Overall, BNPratio was a powerful, independent predictor of mortality (hazard ratio: 1.33 [95% confidence interval: 1.15 to 1.54]; p 0.0001), whereas absolute BNP was not (p = 0.43). In patients who were initially treated medically (n = 770; 58%), BNPratio was a powerful, independent, and incremental predictor of mortality after diagnosis (hazard ratio: 1.61 [95% confidence interval: 1.34 to 1.93]; p 0.0001). Higher BNP activation was associated with higher mortality (p 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. After initial surgical treatment (n = 561, 42%) BNP activation did not impose excess long-term mortality (p = 0.23).In patients with degenerative MR, BNPratio is a powerful, independent, and incremental predictor of long-term mortality under medical management. BNPratio should be incorporated into the routine clinical assessment of patients with degenerative MR.

BACKGROUND: Gadolinium (Gd) Extracellular volume fraction (ECV) by Cardiovascular Magnetic Resonance (CMR) has been proposed as a non-invasive method for assessment of diffuse myocardial fibrosis. Yet only few studies used 3 T CMR to measure ECV, and the accuracy of ECV measurements at 3 T has not been established. Therefore the aims of the present study were to validate measurement of ECV by MOLLI T1 mapping by 3 T CMR against fibrosis measured by histopathology. We also evaluated the recently proposed hypothesis that native-T1 mapping without contrast injection would be sufficient to detect fibrosis. METHODS: 31 patients (age = 58 ± 17 years, 77% men) with either severe aortic stenosis (n = 12) severe aortic regurgitation (n = 9) or severe mitral regurgitation (n = 10), all free of coronary artery disease, underwent 3 T-CMR with late gadolinium enhancement (LGE) and pre- and post-contrast MOLLI T1 mapping and ECV computation, prior to valve surgery. LV biopsies were performed at the time of surgery, a median 13 [1-30] days later, and stained with picrosirius red. Pre-, and post-contrast T1 values, ECV, and amount of LGE were compared against magnitude of fibrosis by histopathology by Pearson correlation coefficients. RESULTS: The average amount of interstitial fibrosis by picrosirius red staining in biopsy samples was 6.1 ± 4.3%. ECV computed from pre-post contrast MOLLI T1 time changes was 28.9 ± 5.5%, and correlated (r = 0.78, p

Background Paradoxical low gradient (PLG) severe aortic stenosis (SAS) is a recently described subset of SAS, which is a matter of intense debate. Some authors indeed consider this new entity as a more advanced form of SAS, whereas others believe the opposite. To get further insight into the pathophysiology of PLG SAS, we compared the weight of the valves explanted at the time of surgery (AVR) and the degree of valve calcification among consecutive patients with PLG SAS and high-gradient (HG) SAS. Methods We prospectively recruited 38 consecutive patients (20 men; mean age: 73 yrs) with isolated non-rheumatic SAS (indexed aortic valve area (AVAi) Results PLG and HG SAS had similar baseline characteristics with the exception of AVAi which was higher (0.44±0.06 vs 0.36±0.10 cm2m2, p=0.008) and MG which was lower (32±7 vs 55±12 mmHg, p 0.90) and in-vivo (r2=0.71) Agatston scores. Interestingly, valves explanted from patients with PLG SAS were lighter (1.58±0.65 vs 2.65±1,24g, p=0.001) and showed lower ex-vivo Agatston scores (363±282 vs 1211±840, p Conclusion The valves weight and degree of valve calcification reported in our study indicate that PLG SAS valves are less severely affected than HG SAS valves. These data thus reinforce the hypothesis that PLG SAS is a lesser advanced form of aortic stenosis than HG SAS.

Background— Up to 30% of patients with severe aortic stenosis (SAS; indexed aortic valve area 2 /m 2 ) present with low transvalvular gradient despite a normal left ventricular ejection fraction. Presently, there is intense controversy as to the prognostic implications of such findings. Accordingly, the aim of the present work was to compare the natural history of patients with paradoxical low-gradient (PLG) or high-gradient (HG) SAS. Methods and Results— We prospectively studied 349 patients with SAS and preserved left ventricular ejection fraction. Patients were categorized into HG-SAS (n=144) and PLG-SAS (n=205) according to mean transvalvular gradient (mean gradient >40 or ≤40 mm Hg). Primary end points were all-cause mortality and echocardiographic disease progression. To evaluate natural history, patients undergoing aortic valve replacement were censored at the time of surgery (n=92). During a median follow-up of 28 months, 148 patients died. Kaplan–Meier survival curves showed better survival in PLG-SAS than in HG-SAS, both in the overall population (48% versus 31%; P P P Conclusions— Our study indicates that PLG-SAS is a less malignant form of AS compared with HG-SAS, because their spontaneous outcome is better. We further demonstrated that patients with PLG-SAS are en route toward the more severe HG-SAS form, because the majority of them evolve into HG-SAS over time.

BackgroundValvular heart disease is associated with left ventricular hypertrophy, remodeling and development of diffuse interstitial fibrosis. So far, histopathology remains the gold standard for evaluating diffuse myocardial fibrosis. Gadolinium enhanced Cardiac Magnetic Resonance (CMR) T1 mapping is new method which allows to quantify the myocardial extracellular volume (ECV). Hence, it was suggested that this ECV measurements allows to non-invasive estimate diffuse fibrosis. However validations studies are scars. Therefore the aim of this study was to validate measurements of ECV by T1-Modified Lock-locker (MOLLI) CMR against histological measurement.Methods and resultsBetween June 2012 and September 2013, 15 patients (age=57±15 years, 73% men) with either severe aortic valve disease (stenosis or regurgitation) or severe mitral regurgitation, but without coronary artery disease preoperatively underwent ECV measurement by CMR MOLLI T1 mapping. LV biopsies were performed at the time of surgery 7±8 days later and stained with Sirius red. The amount of fibrosis quantified by biopsy was 6.6±4.8% [2.1;15.9]. ECV by T1 mapping was 28.3±4.7% [23.3;38.6] (values are presented as mean±SD [min;max]). There was a good correlation between histologically measured fibrosis and T1 mapping ECV (r=0.77, p