Virginia Nguyen

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±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/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±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/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 Differences in the Progression of Aortic Stenosis and Prognostic Implication: The COFRASA-GENERAC Study.

In patients with aortic stenosis (AS), degree of aortic valve calcification (AVC) measured using multislice computed tomography is closely related to hemodynamic severity as assessed using transthoracic echocardiography [(1)][1]; but for similar hemodynamic severity, AVC load is lower in females

Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis

BACKGROUND Determinants of the progression of aortic stenosis (AS) remained unclear. Metabolic syndrome (MetS) and diabetes are suspected to play an active role but literature is scarce and results conflicting. We sought to assess their impact in an ongoing prospective cohort of asymptomatic patients with at least mild AS. METHODS We enrolled 203 patients (73±9years, 75% men) with at least 2years of follow-up. Risk-factors assessment was performed at baseline. Annual progression was calculated as [(final-baseline measurements)/follow-up duration] for both mean pressure gradient (MPG) and degree of aortic valve calcification (AVC) measurements. RESULTS Ninety-nine patients (49%) had MetS and 50 (25%) had diabetes (including 39 with MetS). After a mean follow-up of 3.2±1.2years, AS progression was not different between patients with and without MetS either using MPG (+3±3 vs. +4±4mmHg/year, p=0.25) or AVC (+211±231 vs. +225±222AU/year, p=0.75). Same results were obtained for patients with diabetes (3±3 vs. 4±4mmHg/year p=0.53, 187±140 vs. 229±248AU/year p=0.99). MetS had no impact on AS progression in all tested subgroups based on age, statin prescription, valve anatomy and AS severity (all p≥0.10). CONCLUSION In our prospective cohort of AS patients, we found no impact of MetS or diabetes on AS progression. Although MetS and diabetes should be actively treated, no impact on AS progression should be expected. Our results support the theory that if cardiovascular risk-factors may play a role at the early phase of AS disease they have no or limited influence on AS progression.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic StenosisCLINICAL PERSPECTIVE

Background— Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Methods and Results— Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126–2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19–6.78]; P<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39–9.73]; P=0.010). Conclusions— Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.

Determinants and prognostic value of B-type natriuretic peptide in patients with aortic valve stenosis

BACKGROUND The prognostic value of N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) in aortic stenosis (AS) is still being debated. We sought to evaluate the determinants of Nt-proBNP in AS and its prognostic value in asymptomatic patients. METHODS Patients with pure isolated at least mild degenerative AS enrolled in our prospective cohort (2006-2013) constituted our population. Clinical and biological measurements as well as echocardiographic evaluations were performed at study entry for all patients. Severe AS was defined by a valve area <1cm2. Asymptomatic patients were contacted every six months and seen every year. The occurrence of AS-related events (sudden death, congestive heart failure or new onset of symptoms) within two years was recorded prospectively. RESULTS We enrolled 809 patients. Nt-proBNP increased with AS severity (p<0.0001) and symptomatic status (p<0.0001) but there was a wide overlap between groups of AS severity or symptomatic status. Nt-proBNP was the result of complex interactions between multiple determinants, including AS severity and symptomatic status but also age (p=0.0008), history of coronary artery disease (p=0.03), rhythm (p=0.007) and diastolic function (p<0.0001). Consequently, in asymptomatic patients with moderate/severe AS, normal ejection fraction and in sinus rhythm, Nt-proBNP was associated with AS-related events in univariate analysis (p=0.009) but not after adjustment for AS severity (p=0.12). Repeated Nt-proBNP measurements at one year did not improve their predictive value (p=0.43). CONCLUSION This study highlights the limitations of Nt-proBNP in AS and raises caution regarding its use, at least as a single factor, in the decision-making process regarding asymptomatic patients with AS.

Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study

Background Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy.

Determinants and Prognostic Value of Longitudinal Strain in Asymptomatic Aortic Stenosis and Preserved Left Ventricular Ejection Fraction—The COFRASA/GENERAC Study

ABSTRACT Background: Longitudinal strain has been proposed as a sensitive marker of left ventricular systolic dysfunction. However its prognostic value in patients with aortic stenosis (AS) remains debated. Methods: In a prospective cohort of asymptomatic patients with at least mild, isolated AS and preserved left ventricular ejection fraction (LVEF), clinical, biological measurements, global longitudinal strain (GLS) and basal longitudinal strain (BLS) were performed at study entry. The occurrence of AS-related events (sudden death, congestive heart failure, new onset of symptoms) or aortic valve replacement within two years was recorded prospectively. Results: A total of 140 patients were enrolled and 21 events occurred. In contrast to GLS, BLS was significantly correlated to AS severity (p = 0.0006 with PV, p = 0.0002 with MPG, p = 0.01 with AVA, and p = 0.0009 with AVAi) and predicted the occurrence of AS-related events in the subset of severe AS in univariate analysis (p = 0.03) and after adjustment for AVA (p = 0.01), AVAi (p = 0.01), PV (p = 0.045), and MPG (p = 0.05). However, there was an important overlap of baseline BLS values between patients who developed symptoms and those who did not and repeated BLS measurements showed no difference between baseline values and those obtained at the time of overt symptoms in nine patients (p = 0.38). Conclusion: BLS was statistically predictive of AS-related events in the subset of severe AS. However, overlap of BLS values between groups of symptomatic status and similar values at baseline and at the time of overt symptoms raise the question of its use at an individual level at least as a single isolated parameter.

Prognostic Value of Combination of Hemodynamic Parameters in Asymptomatic Aortic Valve Stenosis—The COFRASA/GENERAC Study

ABSTRACT Background: Whether risk-stratification in aortic valve stenosis (AS) should rely on a single hemodynamic parameter or a combination of hemodynamic parameters is still debated. We aimed to evaluate the prognostic value of mean pressure gradient (MPG), aortic valve area (AVA), and the dimensionless index (DI) in patients with AS and to test whether their combination provides additional prognostic information. Methods: We enrolled 319 asymptomatic patients with AS (90 mild, 173 moderate, and 56 severe AS). All patients were prospectively followed on a yearly basis and AS-related events (sudden death, heart failure, or new onset of AS-related symptoms) were collected. Results: After a mean follow-up of 3.1±1.7 years, an AS-related event occurred in 84 patients (26%). When considered in isolation, after adjustment for age, sex, history of coronary artery disease, valve anatomy, and left ventricular ejection fraction, each parameter (MPG, AVA, and DI) independently predicted the occurrence of AS-related events (all p<0.0001). When considered in combination, MPG and AVA (p=0.0009 and p<0.0001 respectively) or MPG and DI (p=0.0001 and p<0.0001 respectively) remained independent predictors of outcome. Results were sustained after exclusion of 31 patients (10%) with discordant grading. Conclusion: In a large prospective cohort of asymptomatic patients with a wide range of AS severity, AVA, MPG, and DI were all important prognostic factors. More importantly, irrespective of the presence of patients with discordant grading, MPG and either the AVA or the DI provided complementary prognostic information. Our results show that these hemodynamic parameters should be considered in combination in the clinical management of AS patients.

Anatomical features of acute mitral valve repair dysfunction: Additional value of three-dimensional echocardiography

Recurrence of mitral regurgitation after mitral valve repair is correlated with unfavourable left ventricular remodelling and poor outcome. This pictorial review describes the echocardiographic features of three types of acute mitral valve repair dysfunction, and the additional value of three-dimensional echocardiography.

0574: Determinants and prognostic value of Galectin-3 in patients with aortic valve stenosis - the COFRASA-GENERAC study

Background Identifying subgroups of asymptomatic patients with aortic stenosis (AS) who may benefit from early intervention is a critical challenge due to the risk of sudden death and irreversible myocardial dysfunction without preceding symptoms. In this study, we analyzed the determinants and prognostic value of Galectin-3 in a large cohort of patients with AS. Methods We included patients with at least mild degenerative AS enrolled in 2 ongoing prospective clinical studies, COFRASA and GENERAC, aiming at assessing the determinants of AS occurrence and progression. Results Between November 2006 and July 2013, 583 patients were prospectively enrolled. Severe AS was diagnosed in 312 (56%) patients among whom 220 (38%) were symptomatic. Age (p No significant association was found between Galectin-3 and echocardio-graphic parameters of AS severity including aortic valve area (p=0.41), mean transvalvular gradient (p=0,27), and AS jet velocity (p=0.52). Galectin-3 did not provide diagnostic evidence of severe AS (area under the curve=0.53). Galectin-3 was not influenced by symptomatic status. Echocardiographic parameters of LV remodeling were not associated with Galectin-3 in multivariate analysis. Event-free survival analysis revealed no prognostic value of Galectin-3. Conclusions The main determinants of Galectin-3 level were age and renal function. There was no association between Galectin-3 and symptomatic status and echocardiographic parameters associated with LV remodeling. Galectin-3 didn’t provide prognostic information on the occurrence of AS related events. These results do not support the use of Galectin-3 in the decision making process of patients with AS.