Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome.

BACKGROUND: Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene. OBJECTIVES: This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter. METHODS: Patients carrying an FBN1 pathogenic variant who visited our reference center at least twice were included, provided they had not undergone aortic surgery or had an aortic dissection before their first visit. Aortic events (aortic surgery or aortic dissection) and deaths were evaluated during the 2 years following each patient visit. The risk was calculated as the number of events divided by the number of years of follow-up. RESULTS: A total of 954 patients were included (54% women; mean age 23 years). During follow-up (9.1 years), 142 patients underwent prophylactic aortic root surgery, 5 experienced type A aortic dissection, and 12 died (noncardiovascular causes in 3, unknown etiology in 3, post-operative in 6). When aortic root diameter was <50 mm, risk for proven type A dissection (0.4 events/1,000 patient-years) and risk for possible aortic dissection (proven aortic dissection plus death of unknown cause, 0.7 events/1,000 patients-years) remained low in this population that was treated according to guidelines. Three type A aortic dissections occurred in this population during the 8,594 years of follow-up, including 1 in a patient with a tubular aortic diameter of 50 mm, but none in patients with a family history of aortic dissection. The risk for type B aortic dissection in the same population was 0.5 events/1,000 patient-years. CONCLUSIONS: In patients with FBN1 pathogenic variants who receive beta-blocker therapy and who limit strenuous exercise, aortic risk remains low when maximal aortic diameter is <50 mm. The risk of type B aortic dissection is close to the remaining risk of type A aortic dissection in this population, which underlines the global aortic risk.

Marfan Sartan: a randomized, double-blind, placebo-controlled trial.

AIMS: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving ß-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION: Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. ß-Blocker therapy alone should therefore remain the standard first line therapy in these patients.

The clinical presentation of Marfan syndrome is modulated by expression of wild-type FBN1 allele.

Marfan syndrome is an autosomal dominant disorder mainly caused by mutations within FBN1 gene. The disease displays large variability in age of onset or severity and very poor phenotype/genotype correlations have been demonstrated. We investigated the hypothesis that phenotype severity could be related to the variable expression level of fibrillin-1 (FBN1) synthesized from the wild-type (WT) allele. Quantitative reverse-transcription and polymerase chain reaction was used to evaluate FBN1 levels in skin fibroblasts from 80 Marfan patients with premature termination codons and in skin fibroblasts from 80 controls. Results in controls showed a 3.9-fold variation in FBN1 mRNA synthesis level between subjects. A similar 4.4-fold variation was found in the Marfan population, but the mean level of FBN1 mRNA was a half of the control population. Differential allelic expression analysis in Marfan fibroblasts showed that over 90% of FBN1 mRNA was transcribed from the wild allele and the mutated allele was not detected. In the control population, independently of the expression level of FBN1, we observed steady-state equilibrium between the two allelic-mRNAs suggesting that FBN1 expression mainly depends on trans-acting regulators. Finally, we show that a low level of residual WT FBN1 mRNA accounts for a high risk of ectopia lentis and pectus abnormality and tends to increase the risk of aortic dilatation.

Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography.

BACKGROUND: Contrast-enhanced computed tomography (CT) is routinely used as a complementary technique to trans-thoracic echocardiography (TTE) for assessing thoracic aortic aneurysms (TAA). However different measures can be obtained on CT and there are no recommendations on which to use. The objective was to determine which CT measurements most closely match reference TTE measurements in Marfan patients with TAA. METHODS: TTE measurements were obtained using the leading edge-to-leading edge technique in end-diastole on the parasternal longitudinal view. ECG-gated CT measurements were obtained, using the inner-to-inner technique in end-diastole by double oblique reconstruction: on three-cavity view (3C), left ventricle-aorta view (LVAo), and strict transverse plane passing through the maximal diameter "cusp to commissure" and "cusp to cusp" for each cusp. CT and TTE were performed within one month. RESULTS: 44 Marfan patients (39 ± 19 years, 48% men) were included. Dilatation of the ascending aorta was maximal at the level of the sinuses (TTE diameters: mean 47.5 ± 5.3 mm). TTE diameters were similar to 3C, LVAo (mean differences: 2.2 and -0.1 mm, p=NS) and to the three "cusp to cusp" diameters (mean differences ranging from 0 to 1.1mm, p=NS), whereas "cusp to commissure" diameters were all statistically smaller than TTE (3.6 mm, 2.9 mm and 3.7 mm, p ≤ 0.01). CONCLUSIONS: Inner-to-inner "cusp to cusp" diameter measured on an ECG-gated CT should be used for comparison with 2D TTE aortic diameter at the level of the sinuses of Valsalva in patients with thoracic aortic aneurysms.

Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy.

BACKGROUND: Bicuspid aortic valve (BAV) is related to aortic dilatation, but patterns/rates are conflicting with no comparison among aneurysms of different aetiology. We sought to define ascending aorta dilatation patterns/progression rates in BAV versus other aortopathies (Marfan syndrome (MFS), degenerative aortopathy (DA)). DESIGN AND SETTING: Retrospective, observational study. Aortic dilatation progression was evaluated in two tertiary care centres (US and European) by repeated echocardiography ≥2 years apart in adults with BAV (n=353), matched to MFS (n=50) and DA (n=51) for gender, blood pressure, and minimum follow-up time. RESULTS: At baseline, ascending aortic dilatation was present in 87% of BAV cases: tubular ascending aorta in 60% (irrespective of BAV morphology), and Valsalva sinuses dilatation in 27% (independently linked to typical BAV morphology and male gender (p=0.0001)). After 3.6±1.2 years, the aortic dilatation rate in BAV was higher than expected for the population for all aortic levels (p=0.005) and was maximal at the tubular ascending aorta for BAV (0.42±0.6 mm/year) and DA (0.20±0.3 mm/year), and was maximal at the Valsalva sinuses for MFS (0.49±0.5 mm/year). Maximal aortic dilatation rate was similar between BAV and MFS (p>0.40) and lower in DA (p=0.02) but was heterogeneous in BAV, with 43% of BAV not progressing (vs 20% of MFS, p=0.01). Aortic dilatation rate was not proportionally related to baseline aortic size or BAV type (all models p>0.40). CONCLUSIONS: In patients with BAV, tubular ascending aorta dilatation is the most common pattern and exhibits the fastest growing rate, irrespective of valve morphology and function. Dilatation of the Valsalva sinuses is less common and associated with typical BAV morphology and male gender. Aortic dilatation progresses equally fast in BAV (tubular segment) and MFS (Valsalva sinuses), but a significantly higher proportion of BAV patients does not progress at all, irrespective of BAV type. Baseline aortic diameter does not proportionally predict progression rate; systematic follow-up is therefore warranted in patients with BAV.

Pregnancy outcomes among women with Marfan syndrome.

OBJECTIVE: To determine cardiac and obstetric outcomes among women with Marfan syndrome (MS) whose pregnancies were managed in accordance with the French national guidelines. METHODS: A descriptive analysis was conducted for a prospective cohort of 18 women with MS who gave birth in the maternity unit of Bichat-Claude Bernard Hospital, Paris, France, between January 1, 1998, and May 31, 2011. The study hospital was the national referral center for MS and related diseases. RESULTS: A total of 22 pregnancies were recorded among the study cohort. Of these, 21 were managed according to the national guidelines. One woman who was referred to the study hospital during late pregnancy was not managed according to the national guidelines; this patient experienced aortic dissection at 37 weeks. In the cohort, aortic diameter did not increase significantly during pregnancy. Vascular fetal growth restriction was observed in 7 (31.8 %) of the pregnancies. Cesarean delivery was planned for 17 (77.3%) of the pregnancies. CONCLUSION: Risk of aortic dissection was low among a cohort of pregnant women with MS who were managed according to the French national guidelines.

Long-term efficacy of percutaneous mitral commissurotomy for restenosis after previous mitral commissurotomy.

OBJECTIVE: We analysed long-term results of percutaneous mitral commissurotomy (PMC) performed because of mitral restenosis after previous commissurotomy. DESIGN: Follow-up of a prospective cohort. SETTING: Tertiary university hospital. PATIENTS: We studied 163 consecutive patients who underwent PMC because of restenosis occurring 16 ± 8 years after previous commissurotomy (closed-heart in 121, open-heart in 30 and PMC in 12). Mean age was 48 ± 14 years; 62 patients (38%) had valve calcification. Restenosis was due to bicommissural fusion in all cases. INTERVENTION: PMC using a single or double balloon in 80 patients and the Inoue balloon in 83. RESULTS: Good immediate results (IR) (valve area ≥ 1.5 cm2 with MR ≤ 2/4) were obtained in 135 pts (83%). 20-year rates were 27.9 ± 4.7% for cardiovascular survival without mitral surgery and 14.8 ± 3.9% for good functional results (cardiovascular survival without reintervention on the mitral valve and in New York Heart Association (NYHA) class I or II). After good IR, 20-year rates were 33.2 ± 5.5% for cardiovascular survival without surgery and 17.9 ± 4.7% for good functional results. After good IR, multivariate predictive factors of poor late functional results were higher NYHA class (p = 0.01), atrial fibrillation (p = 0.0002) and higher mean mitral gradient after PMC (p = 0.004). CONCLUSIONS: In patients with restenosis after mitral commissurotomy, PMC provides good IR in most cases. After good IR, one patient out of three remains free from surgery and one out of five has good functional results at 20 years. These findings support the use of PMC after previous commissurotomy, particularly in selected patients with few symptoms and in sinus rhythm.

Reinterventions after percutaneous mitral commissurotomy during long-term follow-up, up to 20 years: the role of repeat percutaneous mitral commissurotomy.

AIMS: We analysed reinterventions performed during long-term follow-up after percutaneous mitral commissurotomy (PMC) with a particular focus on freedom from mitral surgery and late results of repeat PMC. METHODS AND RESULTS: In 912 patients who had good immediate results of PMC (valve area ≥1.5 cm² with mitral regurgitation ≤2/4), we analysed survival without reintervention (surgery or repeat PMC) and survival without surgery alone, with a follow-up up to 20 years. The median age was 48 years, and 251 patients (27%) had calcified valves. During a median follow-up of 12 years, 351 patients (38%) underwent a reintervention: surgery was performed in 266 (76%) patients and repeat PMC in 85 (24%). Cardiovascular survival without reintervention (surgery or repeat PMC) was 38 ± 2% at 20 years. When analysing cardiovascular survival without surgery, this rate increased to 46 ± 2% at 20 years. In the 504 patients aged <50 years at the time of their initial PMC, 20-year rates were 45 ± 3% for cardiovascular survival without reintervention and 57 ± 3% for cardiovascular survival without surgery. Of the 85 patients who underwent repeat PMC, cardiovascular survival without surgery was 60 ± 7% at 10 years. CONCLUSION: After successful PMC, reintervention is frequently needed. However, almost half of the patients remained free from surgery at 20 years. Repeat PMC was performed in one out of four cases of reintervention in this study, thereby allowing for postponement of surgery in a substantial number of patients.

TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome.

A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2. These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations. TGFB2 encodes transforming growth factor (TGF)-ß2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-ß2 expression and immunostaining. Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-ß2 levels leading to a secondary increase in TGF-ß2 production in the diseased aorta.

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.

Late results of percutaneous mitral commissurotomy up to 20 years: development and validation of a risk score predicting late functional results from a series of 912 patients.

BACKGROUND: Long-term follow-up after percutaneous mitral commissurotomy enables predictive factors of late results to be identified. METHODS AND RESULTS: Late results of percutaneous mitral commissurotomy were assessed in 1024 consecutive patients. Good immediate results, defined as valve area ≥1.5 cm(2) without mitral regurgitation >2/4, were obtained in 912 patients (89%). These 912 patients were randomly split into 2 cohorts comprising 609 and 303 patients that were used to develop and validate, respectively, a scoring system predicting late functional results. The 20-year rate of good functional results (survival without cardiovascular death, mitral surgery, or repeat percutaneous mitral commissurotomy and in New York Heart Association class I or II) was 30.2 ± 2.0%. A multivariable Cox model identified 7 predictive factors of poor late functional results: higher final mean gradient (P<0.0001), interaction between age and final mitral valve area (P<0.0001) showing that the impact of valve area decreases with age, interaction between sex and valve calcification (P<0.0001) showing that the impact of valve anatomy is stronger in men, and interaction between rhythm and New York Heart Association class showing an impact of New York Heart Association class only in patients in atrial fibrillation (P<0.0001). A 13-point score enabled 3 risk groups to be defined, corresponding to predicted good functional results of 55.1%, 29.1%, and 10.5% at 20 years in the validation cohort. CONCLUSIONS: Twenty years after percutaneous mitral commissurotomy in a population of patients with varied characteristics, 30% still had good functional results. Prediction of late functional results is multifactorial and strongly determined by age and the quality of immediate results. A simple validated scoring system is useful for estimating individual patient outcome.

Surgical management of patients with Marfan syndrome: evolution throughout the years.

AIM: To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome. METHODS: This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de référence national pour le syndrome de Marfan et apparentés and underwent a surgical event before or during follow-up in the centre. RESULTS: One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010. Aortic surgery was performed in 249 patients (22.7%; 20 children and 229 adults), including the Bentall procedure in 140 patients (56%) and valve-sparing surgery in 88 patients (35%); a supracoronary graft was performed in 19 patients (7.6%), usually for aortic dissection. During the past 20 years, the predominant reason for aortic surgery has switched from aortic dissection to aortic dilatation, while age at surgery has tended to increase (from 32.4 ± 11.9 years to 35.2 ± 12.4 years; P=0.075). Mitral valve surgery was performed in 61 patients (5.6%; six children and 55 adults), including 37 valvuloplasties (60.6%) and 18 mitral valve replacements (29.5%). No significant difference was observed when comparing mitral valve surgery before and after 2000. CONCLUSION: Surgery performed in patients with Marfan syndrome has switched from emergency surgery for aortic dissection to elective surgery for aortic dilatation; this is associated with surgery performed at an older age despite the indication for surgery having decreased from 60mm to 50mm. No significant evolution was observed for mitral valve surgery.

Respective effects of early cerebral and abdominal magnetic resonance imaging on clinical decisions in infective endocarditis.

AIMS: Extracardiac complications of endocarditis influence diagnosis, therapeutic plans, and prognosis. The aim of this study was to assess how early combined cerebral and abdominal magnetic resonance imaging (MRI) affects the diagnosis and management of adults with endocarditis. METHODS AND RESULTS: In a single-centre prospective study, 58 patients with endocarditis underwent systematic cerebral and abdominal MRI within 7 days following admission. Diagnostic classification (Duke's modified criteria) and therapeutic plans were established by two experts just before and after MRI and then compared. Endocarditis was initially classified as definite in 29 patients, possible in 27, and excluded in 2. MRI detected cerebral lesions in 47 patients (81%) (ischaemic lesions in 25, microbleeds in 32, and silent aneurysms in 6), and abdominal lesions in 20 patients (34%). Based solely on MRI results without taking microbleeds into account, experts upgraded endocarditis diagnostic classification in 8 out of 29 (28%) non-definite endocarditis cases either to definite in 6 or to possible in 2. This upgrading was exclusively due to cerebral MRI in four patients and to cerebral and/or abdominal MRI in four patients. Experts modified endocarditis therapeutic plans in 11 (19%) out of the 58 patients, based solely on cerebral MRI, including modification of surgical plans in six (10%) patients. Overall, early MRI led experts to modify classification and/or therapeutic plans in 16 (28%) patients. CONCLUSION: MRI identified cerebral and/or abdominal asymptomatic lesions in many patients with endocarditis, but more frequently cerebral. Both cerebral and abdominal MRI findings affected diagnosis, but only cerebral MRI affected clinical management plans. CLINICALTRIALS.GOV IDENTIFICATION NUMBER: NCT 00144885. IRB AUTHORIZATION NUMBER: 0511114 (Comité Protection des Personnes Paris-Ile de France 1).

Aortic event rate in the Marfan population: a cohort study.

BACKGROUND: Optimal management, including timing of surgery, remains debated in Marfan syndrome because of a lack of data on aortic risk associated with this disease. METHODS AND RESULTS: We used our database to evaluate aortic risk associated with standardized care. Patients who fulfilled the international criteria, had not had previous aortic surgery or dissection, and came to our center at least twice were included. Aortic measurements were made with echocardiography (every 2 years); patients were given systematic ß-blockade and advice about sports activities. Prophylactic aortic surgery was proposed when the maximal aortic diameter reached 50 mm. Seven hundred thirty-two patients with Marfan syndrome were followed up for a mean of 6.6 years. Five deaths and 2 dissections of the ascending aorta occurred during follow-up. Event rate (death/aortic dissection) was 0.17%/y. Risk rose with increasing aortic diameter measured within 2 years of the event: from 0.09%/y per year (95% confidence interval, 0.00-0.20) when the aortic diameter was <40 mm to 0.3% (95% confidence interval, 0.00-0.71) with diameters of 45 to 49 mm and 1.33% (95% confidence interval, 0.00-3.93) with diameters of 50 to 54 mm. The risk increased 4 times at diameters ≥50 mm. The annual risk dropped below 0.05% when the aortic diameter was <50 mm after exclusion of a neonatal patient, a woman who became pregnant against our recommendation, and a 72-year-old woman with previous myocardial infarction. CONCLUSIONS: Risk of sudden death or aortic dissection remains low in patients with Marfan syndrome and aortic diameter between 45 and 49 mm. Aortic diameter of 50 mm appears to be a reasonable threshold for prophylactic surgery.

Mitral regurgitation in patients referred for transcatheter aortic valve implantation using the Edwards Sapien prosthesis: mechanisms and early postprocedural changes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative to conventional surgery in high-risk patients with severe aortic stenosis (AS), but data regarding mitral regurgitation (MR) characteristics and changes after TAVI are sparse. METHODS: A total of 254 patients with severe AS referred for TAVI were prospectively enrolled. Comprehensive echocardiography was performed at baseline and at 7 days and 1 month in patients who underwent TAVI. MR was semiquantitatively graded from 0 to 4. Overlap of the anterior mitral leaflet and the device was measured using transesophageal echocardiography immediately after TAVI. RESULTS: At screening, MR was absent in 26%, grade 1 in 44%, grade 2 in 25%, and grade ≥3 in 5% and was organic in 68% and functional in 32%. TAVI was finally performed using the Edwards Sapien valve in 119 patients, including four with MR grade ≥ 3. MR grade significantly decreased at 7 days (P = .003) but remained unchanged at 1 month (P = .55), whereas reverse remodeling occurred only at 1 month (improvements in left ventricular [LV] end-systolic diameter and ejection fraction; P < .05 for both). MR changes over time significantly differed according to ejection fraction and LV diameters (all P values for interaction < .005) but not according to aortic mean gradient, MR etiology, or overlap of the anterior mitral leaflet and the device (all P values for interaction > .15). CONCLUSIONS: In patients referred for TAVI, MR is common, mainly organic, and rarely severe. After TAVI, MR improved within 7 days in both organic and functional MR, was not influenced by overlap of the anterior mitral leaflet and the device, but was associated with improvement in LV ejection fraction. Possible MR improvement should be taken into account in patient selection for TAVI especially, in cases of LV dysfunction or enlargement and MR of borderline severity.

Comparison of semiquantitative and quantitative assessment of severity of aortic regurgitation: clinical implications.

BACKGROUND: Recent studies have emphasized the importance of quantitative assessment of the degree of aortic regurgitation (AR). However, semiquantitative methods have remained mainly used despite their unclear diagnostic value. The aim of this study was to define the sensitivity and specificity of semiquantitative methods compared with the proximal isovelocity surface area method as a reference for the diagnostic of severe AR. METHODS: The degree of AR was evaluated using the proximal isovelocity surface area method and four semiquantitative measurements (left ventricular cardiac output, pressure half-time, diastolic flow reversal, and vena contracta) in 224 patients with a wide range of AR severity. RESULTS: The mean effective regurgitant orifice area was 25 ± 14 mm(2) (range, 3-69 mm(2)), the mean regurgitant volume was 57 ± 31 mL (range, 9-183 mL), and 100 patients (44%) had severe AR (effective regurgitant orifice area ≥ 30 mm(2) or regurgitant volume ≥ 60 mL). Overall, semiquantitative methods had good specificity but poor sensitivity, except the vena contracta, which had good sensitivity and specificity. Sensitivity, specificity, and positive and negative predictive values of the recommended thresholds for severe AR of the four semiquantitative methods were 53%, 89%, 77%, and 73% for left ventricular cardiac output ≥ 10 L/min; 12%, 100%, 100%, and 52% for pressure half-time < 200 msec; 45%, 87%, 79%, and 60% for diastolic flow reversal ≥ 18 cm/sec; and 81%, 83%, 78%, and 85% for vena contracta ≥ 6 mm, respectively. CONCLUSIONS: For the assessment of AR severity, current thresholds appear specific but poorly sensitive, except for vena contracta, which provides good discriminative value. Semiquantitative methods should be integrated into the comprehensive evaluation of AR severity, but severe AR should not be excluded only on the basis of semiquantitative criteria. These results emphasize the need for the quantitative assessment of AR severity.