Measurements of aortic valve calcium by multidetector computed tomography : implication for the evaluation of paradoxical low-gradient aortic stenosis

Aortic stenosis is a major public health problem with high prevalence, morbidity, and mortality. It is generally caused by progressive thickening and calcification of the aortic valve. To date, the only treatment that can significantly improve the prognosis remains aortic valve replacement. As guidelines recommend performing surgery when aortic stenosis becomes severe and symptomatic, accurate assessment of its severity is a crucial step in the clinical decision-making process. “Paradoxical low-gradient aortic stenosis” is characterized by discrepancies in echocardiographic grading criteria, raising uncertainties about its actual severity and subsequently about its therapeutic management. The aims of this thesis work are to undertake further investigation about the characterization of the paradoxical low-gradient aortic stenosis entity and to improve true-severe aortic stenosis diagnosis using aortic valve calcium load measurements by multidetector computed tomography.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201

Very Long Term Survival After Mitral Repair Vs Replacement. A Propensity Score Analysis Of A Large, Prospective, Multicenter International Registry

Background: Despite the absence of randomized studies comparing mitral valve (MV) repair and replacement, international guidelines strongly recommend MV repair as the optimal surgical treatment for severe degenerative mitral regurgitation (dMR). Yet, the level of evidence supporting these recommendations is low, owing to the lack of available clinical trial data. In this context, analysis of large multicenter registries becomes critical. Objective: To compare very long-term survival among patients (pts) undergoing MV repair versus replacement for the treatment of severe dMR using the technique of propensity score (PS) matching to reduce bias in non-randomized cohorts. Methods: The Mitral Regurgitation International DAtabase (MIDA) is a prospective multicenter registry that includes 2,569 consecutive pts with dMR, who were recruited in 6 tertiary centers (France, Italy, Belgium, and the United States) between 1980 and 2005. Among these, we identified 1,922 pts who underwent mitral surgery, including 1,709 MV repairs and 213 MV replacements. We compared operative mortality and overall survival in both the entire study population and in 615 PS-matched (2:1) pts. Results: Operative mortality was lower after MV repair than after MV replacement, both in the entire population (2 vs 7%; p=0.001) and in the PS-matched pts (4 vs 8%; p=0.04). Similarly, 20-year survival was better after MV repair than after MV replacement, both in the entire population (46% [95% CI, 39%-52%] vs 23% [95% CI, 14%-32%], p<0.001) and in the PS-matched pts (41% [95% CI, 28%-54%] vs 24% [95% CI, 14%-33%], p<0.001). Similar results were obtained in pts aged < 65 years (p<0.005), 65-74 years (p<0.001) and ≥ 75 years (p<0.001). Conclusions: Among registry pts with dMR, performance of MV repair resulted in lower operative mortality and greater long-term survival compared to MV replacement, thus supporting current international recommendations

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

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

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 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

Valve Weight and Severity of Valve Calcification are less in Paradoxical Low Gradient than in High Gradient Severe Aortic Stenosis

Background: Paradoxical low gradient (PLG) severe aortic stenosis (SAS) is a recently described subset of SAS, whose exact clinical significance is a matter of intense debate. Some authors indeed consider this new entity as a more advanced form of SAS, whereas others believe it represents a relatively benign form of AS. 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, two surrogates markers of the true stenosis severity, 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) 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±1.24 g, p=0.001) and showed lower ex-vivo Agatston scores (363±282 vs 1211±840, p<0.001) than HG SAS valves. These differences remained significant after adjustment for gender (1.58±0.65 vs 2.36±0.88 g, p=0.011 for valves weight and 363±282 vs 1023±597, p=0.002 for ex-vivo Agatston score). 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

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

Is paradoxical Low Gradient severe Aortic Stenosis a More Advanced form of Aortic Stenosis? New Insights gained from measurements of Valvular Calcium Content by use of 256-slice MDCT.

Background: Paradoxical low gradient severe aortic stenosis (PLG SAS) is a recently described subset of aortic stenosis (AS) the clinical and prognostic implications of which are a matter of intense debate. Some authors indeed consider this new entity as a more advanced form of AS, with increased interstitial fibrosis, reduced LV longitudinal function and poor prognosis, whereas others believe it represents a relatively benign form of AS, with an outcome similar to that of moderate AS. Because the severity of degenerative AS is intimately correlated with its calcium content, the aim of the present work was to directly compare the degree of valve calcification among PLG SAS and high-gradient (HG) SAS. Methods: Forty three consecutive patients (16 men; mean age: 74±9 years) with isolated non-rheumatic SAS, preserved LVEF and regular sinusal rhythm underwent 256-slice MDCT to measure aortic valve calcium within 15 days of their echocardiographic examination. Patients were categorised according to mean transaortic gradient (MG) into PLG SAS (n=14, MG≤40 mmHg) or HG SAS (n=29, MG>40mmHg). Aortic valve calcification was assessed by use of the Agatston score. Analyses were conducted in the entire population as well as in subsets of patients matched for indexed aortic valve area (AVAi) and gender. Results: With the exception of MG which by definition, was lower in PLG SAS than in HG SAS (30±5 vs 57±14 mmHg), PLG and HG SAS had similar baseline clinical and echocardiographic characteristics. In particular AS severity, as evaluated by the AVAi was similar in both groups (0.41±0.10 vs 0.36±0.08 cm2/m2, p=ns). By contrast, the Agatston score was significantly lower in PLG SAS than HG SAS (1684±859 vs 3209±1530, p≤0.001). This difference remained significant after matching the patients for AVAi and gender (1657±850 vs 2592±774, p=0.017). Conclusion: Patients with PLG SAS display less calcified aortic valves by MDCT than patients with HG SAS. This suggests that the aortic valve disease process is less advanced in PLG SAS than in HG SAS

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 tim