Caroline Cueff

Feasibility and Outcomes of Transcatheter Aortic Valve Implantation in High-Risk Patients With Stenotic Bicuspid Aortic Valves

Little is known about transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve stenosis, which usually represents a contraindication. The aim of this study was to assess the feasibility and the results of TAVI in this patient subset. Of 316 high-risk patients with severe aortic stenosis who underwent TAVI from January 2009 to January 2012, 15 (5%) had documented bicuspid aortic valves. They were treated using a transarterial approach, using the Medtronic CoreValve system. Patients were aged 80 ± 10 years, in New York Heart Association functional classes III and IV. The mean aortic valve area was 0.8 ± 0.3 cm(2), and the mean gradient was 60 ± 19 mm Hg. The mean calcium score, calculated using multislice computed tomography, was 4,553 ± 1,872 arbitrary units. The procedure was successful in all but 1 patient. Major adverse events, according to Valvular Academic Research Consortium definitions, were encountered in 1 patient (death). The mean postimplantation prosthetic gradient was 11 ± 4 mm Hg, and ≤1+ periprosthetic leaks were observed in all but 2 patients. The mean prosthetic ellipticity index was 0.7 ± 0.2 at the level of the native annulus and 0.8 ± 0.2 at the level of the prosthetic leaflets. After a mean follow-up period of 8 ± 7 months, 1 patient had died from aortic dissection; there were no additional adverse events. All but 2 hospital survivors were in New York Heart Association class I or II. In conclusion, the present series suggests that transarterial Medtronic CoreValve implantation is feasible in selected patients with bicuspid aortic valve and may lead to short-term hemodynamic and clinical improvement.

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.

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.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. # CLINICAL PERSPECTIVE {#article-title-37}

Size-Adjusted Left Ventricular Outflow Tract Diameter Reference Values: A Safeguard for the Evaluation of the Severity of Aortic Stenosis

OBJECTIVE We sought to evaluate the relationship among left ventricular outflow tract diameter (LVOTd), gender, and body surface area (BSA) and to evaluate the usefulness of size-adjusted LVOTd reference values in patients with aortic stenosis (AS). AS grading is based on the echocardiographic calculation of the aortic valve area (AVA) and requires LVOTd measurements, one main potential source of error. Transesophageal echocardiography (TEE) is reputed to be more accurate than transthoracic echocardiography (TTE), but validation studies are rare. A safeguard for LVOTd measurements is thus desirable. METHODS Since January 2006, 3 subsets of patients have been prospectively and concurrently enrolled: 1) TEE group: In 120 patients with and without AS, we prospectively measured LVOTd during both TTE and TEE. 2) Validation set: In 382 patients without aortic valve or ascending aorta diseases, we evaluated the relationship among LVOTd, gender, and BSA. 3) Testing set: In 173 patients with AS, we compared the AVA obtained using measured LVOTd (AVA(MEAS)) and calculated LVOTd derived from a regression determined in the validation set (AVA(CALC)). RESULTS TTE did not differ from and correlated well with TEE measurements overall (23 +/- 2 mm vs 23 +/- 2 mm, P = .26; r = 0.95, P < .0001) and in patients with AS (N = 43) (24 +/- 2 mm vs 24 +/- 3 mm, P = .15; r = 0.92, P < .0001). LVOTd was linearly correlated to BSA independently of gender (LVOTd = 5.7 * BSA+12.1; r = 0.55, P < .0001). In the testing set, AVA(CALC) did not differ from and correlated well with AVA(MEAS) (1.20 +/- 0.42 cm2 vs 1.23 +/- 0.40 cm2; P = .08; r = 0.89; P < .0001). CONCLUSION TTE and TEE measurements of the LVOTd provided similar results. LVOTd was significantly associated to BSA and LVOTd, derived from a linear regression linked to BSA independently of gender, provided an acceptable approximation of the AVA. Thus, although accurate measurement of LVOTd is a crucial part of the echocardiographic evaluation of AS severity, the present equation may be used as a safeguard when this measurement is difficult or not possible with TTE.

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.

Transarterial Medtronic CoreValve System Implantation for Degenerated Surgically Implanted Aortic Prostheses

Background— To assess the results of transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve System (MCS), through the transarterial approach, in high-risk patients with degenerated surgically implanted aortic bioprostheses (SP). Methods and Results— Of 241 patients who underwent TAVI, 10 (4%) had a degenerated SP. The approach was percutaneous transfemoral in 9 cases and surgical transaxillary in 1. Patients were age 75±10 years of age. All were in New York Heart Association classes III or IV and at high risk for repeated surgery. Seven patients had stented, 2 stentless, and 1 homograft SP. The failure mode was predominant regurgitation in 7 cases and stenosis (aortic valve area, 0.7±0.2 cm2; mean gradient, 58±16 mm Hg) in 3. Based on the echographic measurements, 8 patients received a 26-mm, and 2 a 29-mm-diameter MCS. Procedural success rate was 100%. There was 1 in-hospital death, 1 stroke with moderate sequelae, and 1 pacemaker implantation. There were no other adverse events at 30 days. The mean postimplantation transprosthetic gradient was 13±7 mm Hg; periprosthetic regurgitation was absent or trivial in 9 cases and grade 2 in 1. After a median follow-up of 5 months, there were no additional adverse events. All but 1 of the hospital survivors were in New York Heart Association classes I or II. Conclusions— These results suggest that transarterial MCS implantation in degenerated SP is feasible and may lead to hemodynamic and clinical improvement in patients who are poor candidates for repeated surgery, pending confirmation in larger series with longer follow-up.

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.

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.

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.

Determinants of regurgitant volume in mitral regurgitation: contrasting effect of similar effective regurgitant orifice area in functional and organic mitral regurgitation

BACKGROUND Quantitative assessment of the severity of mitral regurgitation (MR) is based on the calculation of the effective regurgitant orifice (ERO), a measure of lesion severity, and of the regurgitant volume (RVol), a measure of left ventricular volume overload. We aimed at evaluating the determinants of RVol in both organic (OMR) and functional mitral regurgitation (FMR). METHODS AND RESULTS MR severity was quantitatively assessed using the proximal isovelocity surface area (PISA) method in 240 patients, 142 with OMR and 98 patients with FMR. By definition, ERO and RVol were strongly correlated both in patients with OMR and FMR (both R = 0.90, P < 0.0001) but the slopes of the regression lines were significantly different (P < 0.0001). This difference remained significant in patients with elevated systolic pulmonary artery pressure (SPAP > 40 mmHg, P < 0.0001) but not in patients with normal SPAP (≤40 mmHg, P = 0.09). In multivariate analysis, independent determinants of RVol were ERO (P < 0.0001), MR mechanism (FMR/OMR) (P = 0.0003) and SPAP (P = 0.03). In patients with elevated SPAP, ERO (P < 0.0001), left ventricular ejection fraction (LVEF) (P = 0.03), and MR mechanism (P = 0.03) were independently associated with RVol, whereas in patients with normal SPAP, ERO (P < 0.0001) was the only independent determinant of RVol. CONCLUSION In the present study, we evaluated the contrasting effect of similar lesion severity in OMR and FMR and showed that similar ERO were associated with lower RVol in FMR compared with OMR. The regurgitant volume is the result of complex interactions of anatomic lesions, LVEF, and SPAP and our results highlight the importance of taking into account these parameters when interpreting RVol values in clinical practice, especially in FMR.