Diagnostic and Prognostic Accuracy of Aortic Valve Calcium Scoring in Patients With Moderate-to-Severe Aortic Stenosis.

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.

Assessment of Left Ventricular Reverse Remodeling by Cardiac MRI in Patients Undergoing Repair Surgery for Severe Aortic or Mitral Regurgitation.

OBJECTIVE: 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. DESIGN: Observational prospective cohort study. SETTING: Single-center, academic, tertiary care cardiovascular center. PARTICIPANTS: Patients and volunteers. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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 <50%) postoperatively. Binary logistic regression analysis indicated preoperative LV volumes as the most accurate parameter for predicting both incomplete LV reverse remodeling in AR and LV dysfunction in MR. Receiver operating characteristic-determined thresholds were LVEDVi >155 mL/m² for AR and >129 mL/m² for MR. CONCLUSION: 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.

Assessment of aortic valve calcium load by multidetector computed tomography. Anatomical validation, impact of scanner settings and incremental diagnostic value.

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.

Impact of left ventricular outflow tract ellipticity on the grading of aortic stenosis in patients with normal ejection fraction.

BACKGROUND: The pathophysiology of paradoxical low-gradient (LG) severe aortic stenosis (SAS) remains controversial. As low transvalvular flow has been implicated, we sought to investigate the impact of left ventricular outflow tract (LVOT) ellipticity on the estimation of the LV stroke volume, the calculation of the aortic valve area (AVA) by use of the continuity equation and on AS severity grading. METHODS: We studied 190 consecutive patients (mean age: 72 ± 13 years; male: 57%) with SAS (indexed AVA < 0.6 cm2/m2) and preserved LV ejection fraction, including 120 patients with severe high gradient (HG) AS and 70 with severe paradoxical LG-AS. AS severity, LV volumes and LVOT ellipticity were assessed by 2D-Doppler echocardiography and cardiac magnetic resonance (CMR). RESULTS: The LVOT exhibited an elliptical shape on CMR images, with a shorter anterior-posterior than median-lateral diameter (2.2 ± 0.2 vs 2.8 ± 0.3 cm, p < 0.01). Accordingly, the LVOT area measured by planimetry was larger than by 2D-echocardiography, assuming a circular orifice (4.9 ± 0.9 cm2 vs 3.7 ± 0.8 cm2, p < 0.01). Inputting the elliptical LVOT area into the continuity equation resulted in a 29% increase in the indexed AVA (from 0.41 ± 0.09 cm2 to 0.54 ± 0.10 cm2). Accordingly, 30 (43%) patients with severe paradoxical LG-SAS were reclassified as having moderate AS. Similar results were obtained when considering 3D-echo for direct planimetry of the LVOT in a subset of 75 patients. CONCLUSIONS: Our results confirm that the LVOT is elliptical in shape and that taking this parameter into account in the calculation of the AVA results in reclassification of 43% of patients with severe paradoxical LG-AS into moderate AS.

Progression of Low-Gradient, Low-Flow, Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction.

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.

Histological Validation of measurement of diffuse interstitial myocardial fibrosis by myocardial extravascular volume fraction from Modified Look-Locker imaging (MOLLI) T1 mapping at 3 T.

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 < 0.001) strongly with the magnitude of histological fibrosis. By opposition, neither amount of LGE (r = 0.17, p = 0.36) nor native pre-contrast myocardial T1 time (r = -0.18, p = 0.32) correlated with fibrosis by histopathology. CONCLUSIONS: ECV determined by 3 T CMR T1 MOLLI images closely correlates with histologically determined diffuse interstitial fibrosis, providing a non-invasive estimation for quantification of interstitial fibrosis in patients with valve diseases. By opposition, neither non-contrast T1 times nor the amount of LGE were indicative of the magnitude of diffuse interstitial fibrosis measured by histopathology.

Natural history of paradoxical low-gradient severe aortic stenosis.

BACKGROUND: Up to 30% of patients with severe aortic stenosis (SAS; indexed aortic valve area <0.6 cm(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<0.01) and in the asymptomatic subgroup (59% versus 35%; P<0.02). In asymptomatic patients, Cox analysis identified age, diabetes mellitus, left atrial volume, and mean gradient as independent predictors of death. Finally, at last echocardiographic follow-up, PLG-SAS demonstrated significant increases in mean gradient (from 29±6 to 38±11 mm Hg; P<0.001). 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.