Marie Annick Clavel

The Complex Nature of Discordant Severe Calcified Aortic Valve Disease Grading : New Insights From Combined Doppler Echocardiographic and Computed Tomographic Study

OBJECTIVESnWith concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected.nnnBACKGROUNDnAortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies.nnnMETHODSnPatients (nxa0= 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi >0.6 cm²/m², MGxa0<40 mm Hg), severe AS (AVAixa0≤0.6 cm²/m², MGxa0≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAixa0≤0.6 cm(2)/m(2), MGxa0<40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MGxa0≥40 mm Hg).nnnRESULTSnThe MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (pxa0< 0.0001) and systemic arterial compliance (pxa0< 0.0001). The AVC-load (median [interquartile range]) was similar within patients with DG (low-MG: 1,619 [965 to 2,528] arbitrary units [AU]; high-MG: 1,736 [1,209 to 2,894] AU; pxa0= 0.49), higher than CG-moderate-AS (861 [427 to 1,519] AU; pxa0< 0.0001) but lower than CG-severe-AS (2,931 [1,924 to 4,292] AU; pxa0< 0.0001). The AVC-load thresholds separating severe/moderate AS were defined in CG-AS with normal flow (stroke-volume-index >35 ml/m(2)). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curvexa0≥0.89, sensitivityxa0≥86%, specificityxa0≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow.nnnCONCLUSIONSnAmong patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients.

Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: Results of an international registry study

BACKGROUNDnAortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical and Doppler echocardiographic AS characteristics, has not been studied.nnnOBJECTIVESnThis study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment.nnnMETHODSnIn 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women.nnnRESULTSnDuring follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, pxa0< 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.04 to 2.92; pxa0= 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; pxa0= 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, pxa0≤ 0.04) and a net reclassification index of 12.5% (pxa0= 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; pxa0= 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; pxa0= 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI.nnnCONCLUSIONSnThis large-scale, multicenter outcomes study of quantitative Doppler echocardiographic and MDCT assessment of AS shows that measuring AVC load provides incremental prognostic value for survival beyond clinical and Doppler echocardiographic assessment. Severe AVC independently predicts excess mortality after AS diagnosis, which is greatly alleviated by AVI. Thus, measurement of AVC by MDCT should be considered for not only diagnostic but also risk-stratification purposes in patients with AS.

Sex differences in aortic valve calcification measured by multidetector computed tomography in aortic stenosis

Background—Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. Methods and Results—We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm2; mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC–AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P=0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm2/m2; P=0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P<0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P<0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P<0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r>0.67; P<0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P⩽0.01). Conclusions—In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.

B-type natriuretic peptide clinical activation in aortic stenosis: Impact on long-term survival

OBJECTIVESnThis study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation andxa0survival after the diagnosis of aortic stenosis (AS).nnnBACKGROUNDnIn AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting ofxa0BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series ofxa0patients have contributed to the uncertainty.nnnMETHODSnA program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.nnnRESULTSnIn 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36xa0±xa019 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (pxa0< 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (pxa0<xa00.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44xa0± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 toxa02.75), and 15 ± 2% with BNP ratio ofxa0≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survivalxa0was confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNPxa0clinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio ofxa0≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (pxa0= 0.54) with BNP ratio ofxa0<2 (HR: 0.68; 95% CI: 0.52 to 0.89; pxa0= 0.003) or BNP ratio ofxa0>2xa0(HR: 0.56; 95% CI: 0.47 to 0.66; pxa0< 0.0001).nnnCONCLUSIONSnIn this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.

Aortic Valve Area Calculation in Aortic Stenosis by CT and Doppler Echocardiography

OBJECTIVESnThe aim of this study was to verify the hypothesis that multidetector computed tomography (MDCT)xa0is superior to echocardiography for measuring the left ventricular outflow tract (LVOT) and calculating thexa0aortic valve area (AVA) with regard to hemodynamic correlations and survival outcome prediction after axa0diagnosis of aortic stenosis (AS).nnnBACKGROUNDnMDCT demonstrated that the LVOT is noncircular, casting doubt on the AVA measurement by 2-dimensional (2D) echocardiography.nnnMETHODSnA total of 269 patients (76 ± 11 years of age, 61% men) with isolated calcific AS (mean gradient 44xa0± 18 mmxa0Hg; ejection fraction 58 ± 15%) underwent Doppler echocardiography and MDCT within the same episode of care. AVA was calculated by echocardiography (AVAEcho) and by MDCT (AVACT) using each technique measurement of LVOT area. In the subset of patients undergoing dynamic 4-dimensional MDCT (nxa0= 135), AVAxa0was calculated with the LVOT measured at 70% and 20% of the R-R interval and measured by planimetry (AVAPlani).nnnRESULTSnPhasic measurements of the LVOT by MDCT yielded slight differences in eccentricity and size (all pxa0< 0.001) but with excellent AVA correlation (rxa0= 0.92, pxa0< 0.0001) and minimal bias (0.05 cm(2)), whereas the AVAPlani showed poor correlations with all other methods (all r valuesxa0<0.58). AVACT was larger than AVAEcho (difference 0.12 ± 0.16 cm(2); pxa0< 0.0001) but did not improve outcome prediction. Correlation gradient-AVA was slightly better with AVAEcho than AVACT (rxa0= -0.65 with AVAEcho vs. -0.61 with AVACT; p = 0.01), andxa0discordant gradient-AVA was not reduced. For long-term survival, after multivariable adjustment, AVAEcho orxa0AVACT were independently predictive (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.13 to 1.42; pxa0<xa00.0001 or HR: 1.18, 95% CI: 1.09 to 1.29 per 0.10 cm(2) decrease; pxa0< 0.0001) with a similar prognostic value (pxa0≥ 0.80). Thresholds for excess mortality differed between methods: AVAEchoxa0≤1.0 cm(2) (HR: 4.67, 95% CI: 2.22 to 10.50; pxa0< 0.0001) versus AVACTxa0≤1.2 cm(2) (HR: 3.16, 95% CI: 1.64 to 6.43; pxa0= 0.005), with simple translation of spline-curve analysis.nnnCONCLUSIONSnHead-to-head comparison of MDCT and Doppler echocardiography refutes the hypothesis of MDCT superiority for AVA calculation. AVACT is larger than AVAEcho but does not improve the correlation with transvalvular gradient, the concordance gradient-AVA, or mortality prediction compared with AVAEcho. Larger cut-point values should be used for severe AS if AVACT (<1.2 cm(2)) is measured versus AVAEcho (<1.0 cm(2)).

Effect of Recurrent Mitral Regurgitation Following Degenerative Mitral Valve Repair: Long-Term Analysis of Competing Outcomes

BACKGROUNDnThe risk for and consequences of recurrent mitral regurgitation (MR) following degenerative mitral valve repair are poorly understood.nnnOBJECTIVESnThis study sought to examine recurrent MR risk along with reoperation and survival rates.nnnMETHODSnWe evaluated patients undergoing primary mitral repair for isolated degenerative MR over 1 decade. Median follow-up was 11.5 years (interquartile range: 9.2 to 13.6 years) and was 99% complete. Multivariate analysis of post-repair MR recurrence employed Cox proportional hazards and multistate modeling.nnnRESULTSnA total of 1,218 patients met the study criteria; the mean age was 64 ± 13 years, mean ejection fraction was 63 ± 9%, and 864 (71%) patients were men. Prolapse was posterior in 62%, bileaflet in 26%, and anterior in 12%. The 15-year incidence of recurrent MR (i.e., MR ≥2) was 13.3%, incidence of mitral reoperation was 6.9%, and overall mortality was 44.0%. Repair before 1996 independently predicted MR recurrence (hazard ratio: 1.52). Additional determinants were: age, mild intraoperative residual MR, anterior leaflet prolapse, bileaflet prolapse, perfusion time >90 min, and lack of annuloplasty. Recurrence of moderate or greater MR was associated with adverse left ventricular remodeling and increased likelihood of death (hazard ratio: 1.72). Among those undergoing repair after 1996, MR recurrence rate was 1.5 per 100 patient-years during the first year post-repair, decreasing markedly to 0.9 thereafter.nnnCONCLUSIONSnOur study demonstrated that recurrent MR following degenerative mitral valve repair is associated with adverse left ventricular remodeling and late death. The incidence of MR recurrence decreases markedly following the first year after intervention. A transparent discussion of recurrent MR risk has pressing relevance when referring patients with complex mitral valve prolapse.

Haemodynamic and anatomic progression of aortic stenosis

Background Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear. Methods In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)). Results After a mean follow-up of 2.9±1.0u2005years, mean MGP increased from 22±11 to 30±16u2005mmu2005Hg (+3±3u2005mmu2005Hg/year), and mean AVC from 1108±891 to 1640±1251u2005AU (arbitrary units) (+188±176u2005AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3u2005mmu2005Hg/year in mild AS, +4±3u2005mmu2005Hg/year in moderate AS and +5±5u2005mmu2005Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p<0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133u2005AU/year in mild AS, +279±189u2005AU/year in moderate AS and +361±293u2005AU/year in severe AS, p<0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p<0.0001). Conclusions AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases. Clinical trial registration COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088).

Sex-related differences in calcific aortic stenosis: correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight

AIMSnCalcific aortic valve stenosis (AS) is purportedly associated with less calcium burden in women than in men. We sought to examine sex-related differences and correlates of surgically excised aortic valve weight (AVW) in pure AS.nnnMETHODS AND RESULTSnClinical and echocardiographic characteristics of 888 consecutive patients who underwent aortic valve replacement for severe AS were correlated to AVW, and in 126 patients, AVW was also correlated to computed tomography aortic valve calcium (AVC) score. Women and men had similar indexed valve area (0.42 ± 0.09 vs. 0.42 ± 0.07 cm (2)/m(2), P = 0.95) and mean systolic gradient (53 ± 15 vs. 52 ± 13 mmHg, P = 0.11), but women had higher New York Heart Association class (2.63 ± 0.70 vs. 2.50 ± 0.70, P = 0.01) and less prevalent coronary artery disease (38 vs. 52%, P < 0.0001). Aortic valve weight was lower in women (1.94 ± 0.88 vs. 3.08 ± 1.32 g, P < 0.0001) even when indexed to body surface area (1.09 ± 0.48 vs. 1.48 ± 0.62 g/m(2), P < 0.0001) or left ventricular outflow tract (LVOT) area (0.54 ± 0.23 vs. 0.71 ± 0.29 g/cm(2), P < 0.0001). Using multivariate analysis, male sex (P < 0.0001), bicuspid valve (P < 0.0001), and larger LVOT area (P < 0.0001) were the major determinants of increased AVW, along with current cigarette smoking (P = 0.007). Diabetes (P = 0.004) and hypertension (P = 0.03) were independently associated with lower AVW. Aortic valve calcium correlated well with AVW (r = 0.81, P < 0.0001) and was lower in women than in men (2520 ± 1199 vs. 3606 ± 1632 arbitrary units, P < 0.0001).nnnCONCLUSIONSnDespite the same degree of AS severity, women have less AVC and lower AVW compared with men, irrespective of valve morphology. Aortic valve calcium is correlated to excised AVW. Hypertension, diabetes, and current cigarette smoking were independently associated with AVW.

Cleft-like indentations in myxomatous mitral valves by three-dimensional echocardiographic imaging

Objectives Cleft-like indentations (CLI) are deep separations between scallops of the mitral posterior leaflet observed in myxomatous mitral valve disease (MMVD), but their diagnosis, mechanisms and implications are unknown. Using 3D transoesophageal echocardiography (3DTOC), we aimed at assessing diagnostic accuracy and defining mechanisms of CLI in patients undergoing surgery for MMVD. Methods 3DTOC of mitral valve was acquired in 49 patients with MMVD and severe regurgitation prior to valve repair. Qualitative review compared 3DTOC diagnosis of CLI with surgical inspection. Mitral, annular and leaflet dimensions were quantified with dedicated software and compared between those with and without CLI. Results Diagnosis of CLI was made by 3DTOC in 17 (35%) while none was identified by 2D and was confirmed in 15 (88%) by surgical inspection. Mechanistically, LV diameters and mitral regurgitant volume (RVol) were similar with and without CLI (p>0.49). Conversely, mitral annulus was smaller with CLI (anteroposterior diameter 42.2±7.1 vs 47.0±7.5u2005mm, p=0.04; circumference 133±16 vs 148±19u2005mm, p=0.009; area 1289±326 vs 1619±427u2005mm2, p=0.008). Prolapse volume tended to be smaller with CLI (1.9±1.2 vs 4.0±4.3u2005mL, p=0.06) involving single posterior scallop at surgery (82% vs 44%, p=0.007) with smaller 3DTOC leaflet area (1574±409 vs 2019±652 mm2, p=0.01). During valve repair, surgical closure of all surgically diagnosed CLI was required. Conclusions Posterior leaflet CLI are frequent in MMVD, are identified by 3DTOC with high accuracy and require closure during valve repair. CLI are mechanistically not related to excess annular enlargement or excess prolapse. Conversely, CLI occur in the context of single scallop prolapse with tissue paucity causing excess separation of scallops. These 3DTOC data enhance diagnostic and mechanistic comprehension of the diversity of MMVD phenotypical presentation.

Mitral Annular Dynamics in Mitral Annular Calcification: A Three-Dimensional Imaging Study

BACKGROUNDnThe mitral annulus displays complex conformational changes during the cardiac cycle that can now be quantified by three-dimensional echocardiography. Mitral annular calcification (MAC) is increasingly encountered, but its structural and dynamic consequences are largely unexplored. The objective of this study was to describe alterations in mitral annular dimensions and dynamics in patients with MAC.nnnMETHODSnTransthoracic three-dimensional echocardiography was performed in 43 subjects with MAC and 36 age- and sex-matched normal control subjects. Mitral annular dimensions were quantified, using dedicated software, at six time points (three diastolic, three systolic) during the cardiac cycle.nnnRESULTSnIn diastole, the calcified annulus was larger and flatter than normal, with increased anteroposterior diameter (29.4 ± 0.6 vs 27.8 ± 0.6 mm, P = .046), reduced height (2.8 ± 0.2 vs 3.6 ± 0.2 mm, P = .006), and decreased saddle shape (8.9 ± 0.6% vs 11.4 ± 0.6%, P = .005). In systole, patients with MAC had greater annular area at all time points (P < .05 for each) compared with control subjects, because of reduced contraction along the anteroposterior diameter (P < .001). Saddle shape increased in early systole (from 10.5% to 13.5%, P = .04) in control subjects but not in those with MAC (P = NS). Valvular alterations were also noted; although mitral valve tent length decreased during systole in both groups, decreases were less in patients with MAC (P < .05 for mid- and late systole). For certain parameters (e.g., annular area), changes were confined largely to those patients with moderate to severe MAC (P = .006 vs control subjects, but nonsignificant for patients with mild MAC).nnnCONCLUSIONSnQuantitative three-dimensional echocardiography provides new insights into the dynamic consequences of MAC. This imaging technique demonstrates that the mitral annulus is not made smaller by calcification. However, there is loss of annular contraction, particularly along the anteroposterior diameter, and loss of early systolic folding along the intercommissural diameter. Associated valvular alterations include smaller than usual declines in tenting during systole. These quantitative three-dimensional echocardiographic data provide new insights into the dynamic physiology of the calcified mitral annulus.