Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia.

BACKGROUND: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. METHODS: Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). RESULTS: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002-1.017], P=0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. CONCLUSIONS: LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.

New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study.

Aims: Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis. Methods and results: We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations. Phenotype was characterized by a comprehensive echocardiography focusing on mitral valve apparatus in comparison with control relatives. In this X-linked disease valves lesions were severe in men and moderate in women. Most men had classical features of mitral valve prolapse (MVP), but without chordal rupture. By contrast to regular MVP, mitral leaflet motion was clearly restricted in diastole and papillary muscles position was closer to mitral annulus. Valvular abnormalities were similar in the four families, in adults and young patients from early childhood suggestive of a developmental disease. In addition, mitral valve lesions worsened over time as encountered in degenerative conditions. Polyvalvular involvement was frequent in males and non-diagnostic forms frequent in females. Overall survival was moderately impaired in men (P = 0.011). Cardiac surgery rate (mainly valvular) was increased (33.3 ± 9.8 vs. 5.0 ± 4.9%, P < 0.0001; hazard ratio 10.5 [95% confidence interval: 2.9-37.9]) owing mainly to a lifetime increased risk in men (76.8 ± 14.1 vs. 9.1 ± 8.7%, P < 0.0001). Conclusion: FLNA-MVD is a developmental and degenerative disease with complex phenotypic expression which can influence patient management. FLNA-MVD has unique features with both MVP and paradoxical restricted motion in diastole, sub-valvular mitral apparatus impairment and polyvalvular lesions in males. FLNA-MVD conveys a substantial lifetime risk of valve surgery in men.

Early structural valve deterioration of Mitroflow aortic bioprosthesis: mode, incidence, and impact on outcome in a large cohort of patients.

BACKGROUND: Structural valve deterioration (SVD) is a major flaw of bioprostheses. Early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, mode, and impact of SVD on outcome in a large series of Mitroflow aortic valve replacement. METHODS AND RESULTS: Six hundred seventeen consecutive patients (aged 76.1±6.3 years) underwent aortic valve replacement with a Mitroflow prosthesis (models 12A/LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), with stenosis as the main mode (n=36). Mean delay to SVD was only 3.8±1.4 years, and 5-year SVD-free survival was 91.6% (95% confidence interval [CI], 88.7-94.7) for the whole cohort and 79.8% (95% CI, 71.2-89.4) and 94.0% (95% CI, 90.3-97.8) for 19- and 21-mm sizes, respectively. Among the 39 patients with SVD, 13 patients (33%) had an accelerated SVD once the mean gradient exceeded 30 mm Hg. Valve-related death was 46.2% in this SVD subgroup. Five-year overall survival was 69.6% (95% CI, 65.7-73.9). In multivariable analysis, SVD was the strongest correlate of overall mortality (hazard ratio=7.7; 95% CI, 4.4-13.6). CONCLUSIONS: Early SVD is frequent in Mitroflow bioprosthesis (models 12A/LX), especially for small sizes (19 and 21 mm), and reduces overall survival. An unpredictable accelerated pattern of SVD constitutes a life-threatening condition. In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent reoperation should be discussed in patients with severe SVD even though they are still asymptomatic.

Calcification of surgical aortic bioprostheses and its impact on clinical outcome.

AIMS: Aortic valve calcification (AVC) of surgical valve bioprostheses (BPs) has been poorly explored. We aimed to evaluate in vivo and ex vivo BP AVCs and its prognosis value. METHODS AND RESULTS: Between 2011 and 2019, AVC was assessed using in vivo computed tomography (CT) in 361 patients who had undergone surgical valve replacement 6.4 ± 4.3 years earlier. Ex vivo CT scans were performed for 37 explanted BPs. The in vivo CT scans were interpretable for 342 patients (19 patients [5.2%] were excluded). These patients were 77.2 ± 9.1 years old, and 64.3% were male. Mean in vivo AVC was 307 ± 500 Agatston units (AU). The AVC was 562 ± 570 AU for the 183 (53.5%) patients with structural valve degeneration (SVD) and 13 ± 43 AU for those without SVD (P < 0.0001). In vivo and ex vivo AVCs were strongly correlated (r = 0.88, P < 0.0001). An in vivo AVC > 100 AU (n = 147, 43%) had a specificity of 96% for diagnosing Stage 2-3 SVD (area under the curve = 0.92). Patients with AVC > 100 AU had a worse outcome compared with those with AVC ≤ 100 AU (n = 195). In multivariable analysis, AVC was a predictor of overall mortality (hazard ratio [HR] and 95% confidence interval = 1.16 [1.04-1.29]; P = 0.006), cardiovascular mortality (HR = 1.22 [1.04-1.43]; P = 0.013), cardiovascular events (HR = 1.28 [1.16-1.41]; P < 0.0001), and re-intervention (HR = 1.15 [1.06-1.25]; P < 0.0001). After adjustment for Stage 2-3 SVD diagnosis, AVC remained a predictor of overall mortality (HR = 1.20 [1.04-1.39]; P = 0.015) and cardiovascular events (HR = 1.25 [1.09-1.43]; P = 0.001). CONCLUSION: CT scan is a reliable tool to assess BP leaflet calcification. An AVC > 100 AU is tightly associated with SVD and it is a strong predictor of overall mortality and cardiovascular events.

Isolated prolapse of the posterior mitral valve leaflet: phenotypic refinement, heritability and genetic etiology.

BACKGROUND: Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved. METHODS: We prospectively enrolled 284 unrelated MVP probands, of whom 178 (63%) had bi-leaflet MVP and 106 had PostMVP (37%). Familial screening within PostMVP patients allowed the identification of 20 families with inherited forms of PostMVP for whom whole genome sequencing was carried out in probands. Functional in vivo and in vitro investigations were performed in zebrafishand in Hek293T cells. RESULTS: In the 20 families with inherited form of PostMVP, 38.8% of relatives had a MVP/prodromal form, mainly of the posterior leaflet, with transmission consistent with an autosomal dominant mode of inheritance. Compared with control relatives, PostMVP family patients have clear posterior leaflet dystrophy on echocardiography. Patients with PostMVP present a burden of rare genetic variants in ARHGAP24. ARHGAP24 encodes the filamin A binding RhoGTPase-activating protein FilGAP and its silencing in zebrafish leads to atrioventricular regurgitation. In vitro functional studies showed that variants of FilGAP, found in PostMVP families, are loss-of-function variants impairing cellular adhesion and mechano-transduction capacities. CONCLUSIONS: PostMVP should not only be considered an isolated degenerative pathology but as a specific heritable phenotypic trait with genetic and functional pathophysiological origins. The identification of loss-of-function variants in ARHGAP24 further reinforces the pivotal role of mechano-transduction pathways in the pathogenesis of MVP. CLINICAL PERSPECTIVE: Isolated posterior mitral valve prolapse (PostMVP), often called fibro-elastic deficiency MVP, is at least in some patients, a specific inherited phenotypic traitPostMVP has both genetic and functional pathophysiological origins Genetic variants in the ARHGAP24 gene, which encodes for the FilGAP protein, cause progressive Post MVP in familial cases, and impair cell adhesion and mechano-transduction capacities.

Machine Learning-Based Phenogrouping in MVP Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events.

BACKGROUND: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment. OBJECTIVES: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis. METHODS: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429, age 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes. RESULTS: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain <21% and indexed LA volume >42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles. CONCLUSIONS: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse, NCT03884426; Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP], NCT02879825).

Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis.

BACKGROUND: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families. METHODS: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband's aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV. RESULTS: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h2 = 0.47, p < 0.0001), in TAV (h2 = 0.49, p < 0.0001) and BAV families (h2 = 0.50, p < 0.0001). The prevalence of BAV in 790 relatives (phenotype cohort) was significantly increased in both TAV and BAV families compared to control families with a prevalence ratio of 2.6 ([95%CI:1.4-5.9]; p = 0.005) and 4.6 ([95%CI:2.4-13.4]; p < 0.0001), respectively. At least one relative had a BAV in 22.2% of tricuspid CAVS families. CONCLUSIONS: Our study confirms the heritability of CAVS in both TAV and BAV families, suggesting a genetic background of this frequent valvular disease. In addition, BAV enrichment in TAV families suggests an interplay between tricuspid CAVS and BAV. Overall results support the need to improve phenotyping (i.e. BAV, TAV, risk factors) in CAVS families in order to enhance the identification of rare and causal genetic variants of CAVS. CLINICAL TRIALS IDENTIFIER: NCT02890407.

Real-time 3D transoesophageal measurement of the mitral valve area in patients with mitral stenosis.

AIMS: Planimetry measured by two-dimensional transthoracic echocardiography (TTE, MVA2D) is the reference method for the evaluation of the severity of mitral stenosis (MS) but requires experienced operators and good echocardiographic windows. Real-time three-dimensional transoesophageal echocardiography (3D-TEE, MVA3D) may overcome these limitations but its accuracy has never been evaluated. METHODS AND RESULTS: We prospectively enrolled 80 patients (58±15 years, 86% female) referred for MS evaluation who underwent, within 1 week, a clinically indicated TTE and TEE. MVA2D was measured by experienced operators (Level III), MVA3D by one experienced and one non-experienced (Level I) operators blinded of any clinical or TTE information. MVA3D measured by the experienced operator [1.11±0.32 cm2; median, 1.1 cm2; range (0.45-2.20)] did not differ from and correlated well with MVA2D [1.10±0.34 cm2; median, 1.05 cm2; range (0.45-2.30)], P=0.87; r=0.79, P<0.0001; ICC=0.79) and mean difference between methods was small (+0.004±0.21 cm2). MVA3D measured by the non-experienced operator [1.08±0.34 cm2; median 1.02 cm2; range (0.45-2.23)] also did not differ from and correlated well with MVA2D measured by experienced operators (P=0.25; r=0.86, P<0.0001; mean difference -0.02±0.18 cm2; ICC=0.86). Intra and interobserver variability were 0.02±0.25 and 0.01±0.33 cm2. CONCLUSION: 3D-TEE provides accurate and reproducible MVA measurements similar to 2D planimetry performed by experienced operators. Thus, 3D-TEE could be considered as a second-line alternative tool for the evaluation of MS severity in patients with poor echocardiographic windows or for team less accustomed to evaluate MS patients.

Sapien 3 Embolization From Ventricle to Aorta in the Setting of Noncalcified Aortic Regurgitation.

Transcatheter aortic valve replacement is currently used off-label for noncalcified aortic valve regurgitation and therefore is restricted to selected cases. In this setting we describe a rare complication of Sapien 3 (Edwards Lifesciences, Irvine, California) embolization from the left ventricle to the descending aorta. Given their technical challenges, such procedures require specific considerations and management. (Level of Difficulty: Advanced.).

Diagnosis of early dysfunction of a tissue mitral valve replacement by three-dimensional transoesophageal echocardiography.

We present the case of a 42-year-old man who underwent tissue mitral valve replacement for symptomatic mitral stenosis. Post-operative course was unremarkable but three-dimensional transoesophageal echocardiography clearly indicated that one cusp had very restricted motion with incomplete opening and premature closure. The cause of this early single cusp failure is unclear. It was not related to flow effects. It is conceivable that cusp failure such as here might contribute towards the degeneration of tissue valve replacements.

French Society of Cardiology guidelines on exercise tests (part 2): Indications for exercise tests in cardiac diseases.

The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject's pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.

Could anticoagulation avoid bioprosthesis subclinical thrombosis in patients undergoing transcatheter aortic valve replacement?

BACKGROUND: Despite a lack of clear evidence, current European guidelines recommend antiplatelet therapy after transcatheter aortic valve replacement (TAVR). Recent investigations suggest that bioprosthesis thrombosis after TAVR is not uncommon and may be prevented by anticoagulation, but not by antiplatelet therapy. AIMS: The study objective was to assess the impact of the antithrombotic regimen on post-TAVR early haemodynamics. METHODS: Patients eligible for TAVR with an Edwards SAPIEN 3 valve were included in this prospective observational study. Patients undergoing long-term anticoagulation before TAVR continued their treatment, whereas previously non-anticoagulated patients received antiplatelet therapy. The primary endpoint was the mean transaortic gradient assessed by transthoracic echocardiography at the first post-TAVR follow-up. Safety was assessed by two composite endpoints: bleeding/vascular complications and major adverse postoperative events. RESULTS: Among 135 included patients, 78 were discharged on antiplatelet therapy and 57 on anticoagulation. Both groups had similar baseline characteristics, except for supraventricular arrhythmia (7.7% on antiplatelets vs. 89.5% on anticoagulation; P<0.001). At 1-2months after TAVR, the mean transaortic gradient was significantly higher in the antiplatelet therapy group versus the anticoagulation group (13.0±4.0 vs. 9.0±2.8mmHg; P<0.001, independently of prosthesis size). Safety analyses showed no significant differences of the composite endpoints. CONCLUSION: Prolonged anticoagulation after TAVR was associated with lower early transaortic gradients than antiplatelet therapy. Anticoagulation treatment may limit clinical and subclinical thrombosis without increasing early postoperative complications.

French Society of Cardiology guidelines on exercise tests (part 1): Methods and interpretation.

The exercise test is still a key examination in cardiology, used for the diagnosis of myocardial ischemia, as well as for the clinical evaluation of other heart diseases. The cardiopulmonary exercise test can further define functional capacity and prognosis for any given cardiac pathology. These new guidelines focus on methods, interpretation and indications for an exercise test or cardiopulmonary exercise test, as summarized below. The safety rules associated with the exercise test must be strictly observed. Interpretation of exercise tests and cardiopulmonary exercise tests must be multivariable. Functional capacity is a strong predictor of all-cause mortality and cardiovascular events. Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the first findings in favor of myocardial ischemia, mostly related to significant coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery, QRS changes (such as enlargement or axial deviations) and the use of scores (based on the presence of various risk factors) must also be considered in exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias or conduction disorders arising during the exercise test must be considered in the assessment of prognosis, in addition to a decrease or low increase in blood pressure during the exercise phase. When performing a cardiopulmonary exercise test, peak oxygen uptake and the volume of expired gas/carbon dioxide output slope are the two main variables used to evaluate prognosis.

Echocardiographic measurement of left atrial volume: Does the method matter?

BACKGROUND: Four two-dimensional echocardiographic methods (cube, ellipsoid, Simpson's and area-length) can be used to assess left atrial volume (LAV). AIMS: To compare absolute LAV measurements and evaluate agreement regarding the semiquantitative assessment of degree of left atrial (LA) enlargement, between methods. METHODS: We prospectively measured LAV in 51 healthy volunteers using the four methods, and defined thresholds for moderate (mean+2 standard deviations [SDs]) and severe (mean+4 SDs) LA enlargement for each method. In 372 patients referred for echocardiography, we compared absolute LAV measurements and agreement between methods. RESULTS: LAV was significantly different between methods in the healthy volunteer group (11 ± 4, 17 ± 3, 26 ± 6 and 28 ± 7 mL/m(2), respectively; P<0.0001), resulting in different thresholds for moderate and severe LA enlargement. LAV was also significantly different in the 372 patients (30 ± 20, 47 ± 27, 61 ± 34 and 65 ± 36 mL/m(2), respectively; P<0.0001). Agreement regarding degree of LA enlargement (none, moderate, severe), using the area-length method as reference, was modest with the cube method (kappa=0.41), correct with the ellipsoid method (kappa=0.60) and excellent with Simpson's method (kappa=0.83). CONCLUSION: The choice of the method had a major effect on assessment of degree of LA enlargement. Our results suggest that the cube and ellipsoid methods, which significantly underestimated LAV and provided modest agreement, should be disregarded. In contrast, Simpson's method and the area-length method were slightly different, but showed close agreement, and should be preferred, using dedicated thresholds (50 and 56 mL/m(2) respectively).

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

BACKGROUND: Aortic 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. OBJECTIVES: This 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. METHODS: In 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. RESULTS: During 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, p < 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; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI. CONCLUSIONS: This 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.

Anatomical features of rheumatic and non-rheumatic mitral stenosis: potential additional value of three-dimensional echocardiography.

Although mitral stenosis is mostly due to rheumatic fever, other etiologies, such as degenerative, congenital, drug- or radiotherapy-induced mitral stenosis, are emerging and need to be recognized in order to decide the best therapeutic options. This pictorial review describes the echocardiographic features of these different anatomical types and the additional value of three-dimensional echocardiography.

Prognostic value of B-type natriuretic peptide in elderly patients with aortic valve stenosis: the COFRASA-GENERAC study.

OBJECTIVE: Previous studies suggested an independent prognostic value of B-type natriuretic peptide (BNP) in aortic valve stenosis (AS) but were impeded by small sample sizes and inclusion of relatively selected young patients. We aimed to evaluate the relationship among N-terminal fragment of proBNP (Nt-proBNP), AS severity, symptoms and outcome in a large cohort of elderly patients with AS. DESIGN: Observational cohort study, COhorte Française de Retrecissement Aortique du Sujet Agé (clinicalTrial.gov number-NCT00338676) and GENEtique du Retrecissement Aortique (clinicalTrial.gov number-NCT00647088). SETTING: Single-centre study. PATIENTS: Patients older than 70 years with at least mild AS. INTERVENTIONS: None. MEASUREMENTS: A comprehensive clinical, biological and echocardiographic evaluation was performed at study entry. Asymptomatic patients were prospectively followed on a 6-months basis and AS-related events (sudden death, congestive heart failure or new onset of AS-related symptoms) collected. RESULTS: We prospectively enrolled 361 patients (79±6 years, 230 severe AS). Nt-proBNP increased with the grade of AS severity and the NYHA class (all p<0.0001) but there was an important overlap between grades/classes. Consequently, diagnostic value of Nt-proBNP for the diagnosis of severe symptomatic AS was only modest (area under the curve of the receiver operator characteristic analysis=0.73). At 2 years, 28 AS-related events occurred among 142 asymptomatic patients prospectively followed. Nt-proBNP was associated with outcome in univariate analysis (p=0.04) but not after adjustment for age, gender and AS severity (p=0.40). CONCLUSIONS: The present study clearly highlights the limitations of Nt-proBNP for the evaluation and management of AS patients. Our results suggest that Nt-proBNP should be considered cautiously, at least as a single criterion, in the decision-making process of AS patients especially in the elderly population.

The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study.

OBJECTIVES: With 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. BACKGROUND: Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies. METHODS: Patients (n = 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, MG <40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm(2)/m(2), MG <40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MG ≥40 mm Hg). RESULTS: The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p < 0.0001) and systemic arterial compliance (p < 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; p = 0.49), higher than CG-moderate-AS (861 [427 to 1,519] AU; p < 0.0001) but lower than CG-severe-AS (2,931 [1,924 to 4,292] AU; p < 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 curve ≥0.89, sensitivity ≥86%, specificity ≥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. CONCLUSIONS: Among 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.

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 cm(2); 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 cm(2)/m(2); 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.