Fibroelastic Deficiency Research Articles

Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging.

Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow's disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment.

Prolapse Volume to Prolapse Height Ratio for Differentiating Barlow’s Disease From Fibroelastic Deficiency

As mitral valve (MV) repair for Barlow's disease remains surgically challenging, it is important to distinguish Barlow's disease from fibroelastic deficiency (FED) preoperatively. We hypothesized that the prolapse volume to prolapse height ratio (PV-PH ratio) may be useful to differentiate Barlow's disease and FED.Methods and Results:In 76 patients with MV prolapse who underwent presurgical transesophageal echocardiography, the 3D MV morphology was quantified: 19 patients were diagnosed with Barlow's disease and 57 with FED. The patients with Barlow's disease had greater prolapse volume and height than the patients with FED, as well as greater PV-PH ratio (0.61±0.35 vs. 0.17±0.10, P<0.001). Receiver-operating characteristic analysis revealed that with a cutoff value of 0.27, the PV-PH ratio differentiated Barlow's disease from FED with 84.2% sensitivity and 84.2% specificity. Net reclassification improvement showed that the differentiating ability of the PV-PH ratio was significantly superior to prolapse volume (1.30, P<0.001). After being adjusted by each of prolapse volume and height, annular area and shape, and the number of prolapsed segments, the PV-PH ratio had an independent association with Barlow's disease. The PV-PH ratio was able to differentiate Barlow's disease from FED with high accuracy. 3D quantification including this value should be performed before MV repair.

Endoscopic atrioventricular valve surgery in adults with difficult-to-access uncorrected congenital chest wall deformities.

This study presents the first report on in-hospital and long-term outcomes of endoscopic port access atrioventricular valve surgery (EPAAVVS) in adult patients with uncorrected congenital chest wall deformities (CCWDs). Our current surgical team performed EPAAVVS in 7 consecutive adult patients (mean age 51.3 ± 16.4 years, 14.3% female, 50% older than 60 years, mean EuroSCORE II 0.8 ± 0.1%) with uncorrected CCWDs between 1 November 2009 and 30 November 2015. The mean left ventricular ejection fraction was 66.0 ± 8.5%. Surgical indications included isolated or combined symptomatic mitral valve (MV) regurgitation (n = 7, 100%), left ventricular outflow tract (LVOT) obstruction (n = 1, 14.3%) and patent foramen ovale (n = 3, 42.9%). Fibro-elastic deficiency accounted for 57.1% of MV pathology and 5 patients (74.1%) presented with New York Heart Association (NYHA) Class III symptoms. CCWDs included isolated pectus excavatum (n = 5, 71.4%) and mixed pectus excavatum and carinatum (n = 2, 28.6%). The mean Haller-index and correction index scores were 2.7 ± 0.5 and 21.4 ± 10.2%, respectively. Procedures performed included MV repair (n = 7, 100%), tricuspid valve (TV) repair (n = 1, 14.3%) and left ventricular septal myomectomy (n = 1, 14.3%). There were no sternotomy conversions or complications with chest wall entry or atrioventricular valve exposure. The mean cardiopulmonary bypass and cross-clamp times were 162.1 ± 48.1 and 113.7 ± 33.5 min, respectively. No patient required mechanical ventilation or intensive care treatment longer than 24 h. There were no surgical revisions, in-hospital respiratory or chest wall morbidities. The mean length of hospital stay was 7.4 ± 1.0 days. A total of 208 patient-months (mean 29.7 ± 26.5) were available for long-term clinical and echocardiographic analysis. There were no 30-day or long-term mortalities and no patient required reintervention for residual atrioventricular valve pathology. All patients were classified as NYHA I during recent consultations, and echocardiographic follow-up confirmed no residual MV regurgitation greater than Grade 1 in any patient. EPAAVVS in adults with uncorrected CCWD is safe, feasible and durable and can successfully be performed by experienced teams to achieve Haller index and correction index scores of up to 3.3 and 38.3%, respectively, with favourable long-term clinical and echocardiographic outcomes. The mere presence of uncorrected CCWDs should not deter surgeons from offering these patients the full benefits of minimally invasive cardiac surgery.

Differential MicroRNA Expression Profile in Myxomatous Mitral Valve Prolapse and Fibroelastic Deficiency Valves.

Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics.

PROLAPSE VOLUME TO PROLAPSE HEIGHT RATIO FOR DIFFERENTIATING BARLOW’S DISEASE FROM FIBROELASTIC DEFICIENCY

Because mitral valve repair for Barlow’s disease (BD) remains a challenge for surgeon, it is important to distinguish BD from fibroelastic deficiency (FED) before surgery. Quantification of mitral valve morphology using three-dimensional transesophageal echocardiography (3DTEE) may help to address

PATTERNS OF LEFT VENTRICULAR REMODELING IN PATIENTS WITH SEVERE DEGENERATIVE MITRAL REGURGITATION: A MULTI-IMAGING STUDY

To determine patterns of LV remodeling in degenerative MR according to valvular phenotypes: myxomatous bileaflet prolapse(MBP) vs. fibroelastic deficiency(FED). Between 2008-2014, 456 consecutive patients with severe degenerative MR underwent cardiac CT prior to robotic mitral valve repair. LV

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies.

0131: A phenotypic study of ARHGAP24 mitral valve prolapse suggests a genetic origin for fibro elastic deficiency

Mitral valve prolapse (MVP) by Barlow disease is recognized a genetic disease. Fibro-elastic deficiency (FED)-MVP is considered a pure degenerative condition. FLNA, the first gene involved in MVP, encodes for Filamin-A, a cytoskeleton associated protein. It interacts with a protein named Filgap, encoded by ARHGAP24 (Chr. 4), in the mechanical transduction. We hypothesized that ARHGAP24 mutations could elicit MVP with same pathway. Four probands with ARHGAP24 mutations were identified among 96 MVP. By a familial echocardiographic screening we enrolled 19 adults of whom 13 had an ARHGAP24 mutation. The mutated group was matched with a control group of 39 healthy adults. Anterior (AML) and posterior (PML) mitral leaflets length and thickness were measured. The coaptation point position was the ratio of coaptation height on the systolic annulus diameter. MVP (displacement >2mm above the annulus line), minimal systolic displacement (MSD, displacement <2mm) and abnormal antero-posterior coaptation position (AAC, ratio <60%) were assessed. The conjunction of MSD and AAC defines a MVP prodromal form (MVP-prod). There was no difference between the two groups on baseline characteristics. Leaflets were thin in the mutated group (PML: 2.7±1 vs 2.2±0.5mm in control, P=0.21, AML: 2.5±0.9 vs 2.1±0.4mm, P=0.25), as reported in FEDMVP. Only the PML was elongated (8.2±1.6 vs 6.0±1.2mm/m 2 , P=0.0003) in the mutated group, leading to an anterior displacement of the coaptation point (51±11 vs 66±7%, P=0.0003). Abnormal mitral phenotype (70% of MVP, 23% of MVP prod) and mitral regurgitation (93 vs 38%, P=0.0007) were frequent in the mutated group. Two probands were operated for severe MR related to chordal rupture; histological examination confirmed the leaflets thinness. ARHGAP24 is the first gene for autosomal dominant inherited MVP. Our limited series of patients exhibit typical features of FED-MVP. Our results could change the paradigm of a pure degenerative disease for FED-MVP.

Three-dimensional dynamic morphology of the mitral valve in different forms of mitral valve prolapse - potential implications for annuloplasty ring selection.

BackgroundReal-time three-dimensional transesophageal echocardiography has increased our understanding of the distinct pathomechanisms underlying functional, ischaemic or degenerative mitral regurgitation. However, potential differences in dynamic morphology between the subtypes of degenerative mitral prolapse have scarcely been investigated.MethodsIn order to compare the dynamic behavior of the different phenotypes of degenerative mitral valve prolapse, real-time three-dimensional transesophageal echocardiography recordings of 77 subjects, 27 with Barlow disease (BD), 32 with Fibroelastic deficiency (FED) and 18 normal controls (NC) were analysed.ResultsGeometric annular and valvular parameters of the myxomatous patients were significantly larger compared to controls (BD vs. FED vs. NC 3D annular area: 15 ± 2.8 vs. 13.3 ± 2.4 vs. 10.6 ± 2.3cm2, all p < 0.01). Beside similar ellipticity, BD annuli were significantly flatter compared to FED. Myxomatous annuli appeared less dynamic than normals, with decreased overall 3D area change, however only the BD group differed from NC significantly (BD vs. FED vs. NC normalized 3D area change 4.40 vs. 6.81 vs. 9.69 %; BD vs. NC p = 0.000; FED vs. NC p = not significant, BD vs. FED p = 0.025).ConclusionBD and FED differ not only in terms of valve morphology, but also annular dynamics. Both pathologies are characterized by annular dilatation. However, in BD the annulus is remarkably flattened and hypodynamic, whereas in FED its saddle-shape and contractile function is relatively preserved. These features might influence the choice of repair technique and the selection of annuloplasty ring.

Young Investigator Award session – Clinical Science442Left bundle branch block and coronary artery disease in coronary ct angiography443Focal myocardial fibrosis and abnormal left ventricular strain in patients with sarcoidosis without clinical evidence of cardiac disease444Arhgap24, a first gene for fibro elastic deficiency mitral valve prolapse? A phenotypic study445Advantage of using ASE/EACVI criteria for detection of subclinical cardiotoxicity in breast cancer

Young Investigator Award session – Clinical Science442Left bundle branch block and coronary artery disease in coronary ct angiography443Focal myocardial fibrosis and abnormal left ventricular strain in patients with sarcoidosis without clinical evidence of cardiac disease444Arhgap24, a first gene for fibro elastic deficiency mitral valve prolapse? A phenotypic study445Advantage of using ASE/EACVI criteria for detection of subclinical cardiotoxicity in breast cancer

Mitral valve repair in fibroelastic deficiency

Fibroelastic deficiency (FED) in the mitral valve might be challenging in certain patients. Leaflets are thin and ruptured chordae are often present. The number of techniques to be applied might be numerous and compromise long-termr esults

ECHOCARDIOGRAPHY PREDICTORS OF SUCCESSFUL MITRAL VALVE REPAIR IN DEGENERATIVE MITRAL VALVE REGURGITATION

Background and aim of the study: Mitral repair is now as the treatement of choice in patients suffering mitral regurgitation due to mitral valve prolapse or flail. However, mitral valve repair demands the mitral valve morphology being feasible for repair. The study aims at evaluating transthoracic and transesophageal echocardiographic features in consecutive patients with mitral valve prolapse or flail undergoing surgical repair at Hue Central Hospital. The correlation between preoperative and intraoperative echocardiographic features and surgical findings in these patients. These echocardiographic data may predict the surgical outcome. Methods: From December 2010 to January 2013, 73 patients (37 men, 36 women; average age 37.5) were recruited into the study. All patients had degenerative mitral valve disease causing important regurgitation and underwent systematic preoperative transthoracic echocardiography, preoperative and intraoperative transesophageal echocardiography for delineation of six segments (scallops) of anterior and posterior leaflets. Results: Among 73 patients, 64 patients were in fibroelastic deficiency (87.7%) and 9 patients suffered Barlow disease (12.3%). Mitral valve repair was performed in 52 patients (71.2%) and mitral replacement was performed in 21 patients (28.8%). All 52 mitral valve repair (81.3%) and 12 mitral valve replacement (18.7%) was performed in fibroelastic deficiency patients. All 9 Barlow patients must undergo mitral valve replacement (100%). A prolapse or flail of mitral valve in 73 patients was documented by transthoracic and transesophageal echocardiography and confirmed on surgical inspection. Accuracy of transthoracic echocardiography was (89.0%) and accuracy of transesophageal echocardiography was (91.8%) in identifying mitral valve segments prolapse or flail. Success rate of mitral valve repair was (98.0%) in prolapse of 1 or 2 segments, but was low (36.0%) in prolapse &gt; 3 segments. Success rate of mitral valve repair was (96.6%) in prolapse of posterior leaflet, but was (63.6%) in prolapse anterior leaflet or bileaflet. Conclusion: - Mitral valve repair was favorable in fibroelastic deficiency patients, but difficult in Barlow patients. - Accuracy of transthoracic and transesophageal echocardiography was high in identifying mitral valve segments prolapse or flail. - Success rate of mitral valve repair was high in prolapse of 1 or 2 segments. - Success rate of mitral valve repair was high in in prolapse of posterior leaflet. Key words: Mitral repair, echocardiography, degenerative, Barlow, fibroelastic deficiency, prolapse, flail

Dynamic phenotypes of degenerative myxomatous mitral valve disease: quantitative 3-dimensional echocardiographic study.

Fibro-elastic deficiency (FED) and diffuse myxomatous degeneration (DMD) are phenotypes of degenerative mitral valve disease defined morphologically. Whether physiological differences in annular and valvular dynamics exist between these phenotypes remains unknown. We performed triple quantitation of cardiac remodeling and of mitral regurgitation severity and of annular and valvular dimensions by real-time 3-dimensional-transesophageal-echocardiography. Forty-nine patients with degenerative mitral valve disease classified as FED (n=31) and DMD (n=18) by surgical observation showed no difference in age (65±10 versus 59±13; P=0.5), body surface area (2.0±0.2 versus 2.0±0.2 m(2); P=0.5), left ventricular and atrial dimensions (all P>0.55), and mitral regurgitation regurgitant orifice (P=0.62). On average, annular dimensions were larger in DMD versus FED, but height was similar resulting in lower saddle shape. Dynamically, annular DMD versus FED display poorer contraction and saddle-shape accentuation in early systole and abnormal enlargement, particularly intercommissural, in late-systole (all P<0.05). Valvular dynamics showed stable valvular area in systole in FED versus considerable systolic increased area in DMD (P<0.001). Prolapse height and volume increased little throughout systole in FED versus marked increase in DMD (P<0.001). Our novel observations show that FED and DMD, although both labeled myxomatous, display considerable physiological phenotypic differences. In DMD, the annular increased size and profoundly abnormal dynamics demonstrate DMD-specific annular degeneration compared with the enlarged but relatively normal FED annulus. DMD does not incur more severe mitral regurgitation, despite larger prolapse and valve redundancy, underscoring potential compensatory role of tissue redundancy of DMD (or aggravating role of tissue paucity of FED) on mitral regurgitation severity.

Left Ventricular Cardiomyopathy in Mitral Valve Prolapse: Fact or Fiction?

In most patients with mitral valve prolapse (MVP) without severe mitral regurgitation (MR), left ventricular (LV) function is preserved. There are, however, patients with MVP who have unexplained LV dilatation and/or decreased LV function. An association between MVP and sudden cardiac death has also been reported. LV size and function may be affected by the type of MVP, severity of regurgitation, and cause of MVP (myxomatous degeneration versus fibroelastic deficiency). There is increasing evidence suggesting an intrinsic cardiomyopathy associated with MVP. The cardiomyopathy associated with MVP can also affect the right ventricle (RV). Although the impact on ventricular dimensions and function are usually subtle, these abnormalities can affect clinical and echocardiographic estimation of the severity of MR and may thus have an impact on therapeutic decisions. Particularly in patients with the most extreme forms of MVP (Barlow disease), and in patients with Marfan syndrome or other connective tissue disorders, a cardiomyopathy affecting the LV and RV may thus occur occasionally. A better understanding of LV impairment associated with MVP is important for risk assessment and clinical decision-making.

Strain balance of papillary muscles as a prerequisite for successful mitral valve repair in patients with mitral valve prolapse due to fibroelastic deficiency

The aim of this study was to assess the papillary muscle strain as a contributor to recurrent mitral regurgitation (MR) after mitral valve repair for fibroelastic deficiency. Sixty-four patients with isolated posterior mitral valve prolapse and severe MR referred for surgery were prospectively recruited between 2008 and 2012. Two- and three-dimensional echocardiography and speckle tracking were performed in all patients. The longitudinal strain of the anterolateral (AL) and posteromedial (PM) papillary muscles was individually calculated as well as the global longitudinal strain of both papillary muscles was measured before and after mitral repair and normalized to left ventricle end-diastolic volume. Eight patients (12.5%) had at least moderate MR 6 months after mitral repair. The longitudinal strain of the AL (preop -4.94 ± 2.2 vs. postop -3.28 ± 1.3, P < 0.001) and the PM papillary muscles (preop -12.64 ± 5.3 vs. postop -4.12 ± 6.77, P < 0.001) as well as the global strain of both papillary muscles (preop -7.59 ± 3.48 vs. postop -1.07 ± 6, P < 0.001) were all reduced after surgical repair. The longitudinal strain of the PM papillary muscle was the strongest predictor of recurrent MR (when less than or equal to -14.78). The global preoperative papillary muscle strain was also a determinant of recurrent MR when the global strain was greater than -9.05% (area under the curve: 0.895, sensitivity: 100%, and specificity: 76.8%). Patients with isolated posterior mitral leaflet prolapse are less likely having any residual MR post repair when the global papillary muscle strain of both papillary muscles is close or equal to zero. Strain of the papillary muscles may be an important determinant in predicting residual MR in patients who undergo mitral valve repair.

Prevalence of Calcification of the Mitral Valve Annulus in Patients Undergoing Surgical Repair of Mitral Valve Prolapse

Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlow's disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated.

Preoperative left ventricular function in degenerative mitral valve disease

The aim of the study is to determine the impact of the underlying etiology (Barlow's disease or fibroelastic deficiency) on left ventricular function in patients with degenerative mitral valve disease and severe mitral regurgitation. We studied 233 patients (mean age: 53.8 ± 12.9) undergoing surgery for severe mitral regurgitation due to degenerative mitral valve disease at Almazov Federal Heart Centre between 2009 and 2011. Pathologic diagnoses for valvular tissue specimens were provided by an experienced pathologist. Preoperative strain and strain rate were determined using speckle tracking (Vivid 7 Dimension, EchoPAC'08). Barlow's disease was identified by the pathologist in 60 patients (25.8%), and fibroelastic deficiency in 173 patients (74.2%). There were no significant differences between groups in preoperative mitral regurgitation volume (70.5 ± 9.6 vs. 71.6 ± 8.5 ml, P = 0.40), and in global systolic (ejection fraction: 52.7 ± 6.6 vs. 52.0 ± 7.4%, P = 0.53) and diastolic (E/e': 12.2 ± 3.9 vs. 12.8 ± 4.2, P = 0.35) left ventricular function. Despite the lack of difference in ejection fraction and diastolic tissue Doppler parameters, in patients with Barlow's disease in comparison with fibroelastic deficiency a significant decrease of the left ventricular longitudinal systolic strain (-13.5 ± 2.2 vs. -15.6 ± 2.3%, P = 0.00001) and early diastolic strain rate (1.04 ± 0.20 vs. 1.14 ± 0.18 s, P = 0.0004) were detected. Patients with severe mitral regurgitation due to Barlow's disease have a lower preoperative left ventricular systolic function than those with fibroelastic deficiency, which may affect their postoperative prognosis.

Clinical and Pathological Features of Degenerative Mitral Valve Disease: Billowing Mitral Leaflet Versus Fibroelastic Deficiency

Degenerative mitral valve disease is distinguished with billowing mitral leaflet (BML) or fibroelastic deficiency (FED). The purpose of this study is to evaluate the clinical characteristics and the pathohistological differences between BML and FED. A total of 73 patients who diagnosed as degenerative mitral valve disease pathologically after mitral valve surgery for severe mitral regurgitation were enrolled. On the basis of echocardiographic features and gross appearances, they were classified as BML (9 cases) and FED (64 cases). In the BML group, multiple segments of the leaflet showed billowing with elongated chordae. Therefore excessive valve tissue needed to be removed by multiple resection and suture. The FED patients had focal myxomatous changes with ruptured chordae, a single resection and suture was frequently employed. In pathological examination, the valve thickness of the BML was nearly twice as thick as the FED, and the mucopolysaccharide accumulation of the Spongiosa in the BML was over 50%, while 30% in the FED. BML presents the characteristic valve thickening due to its abnormal production of mucopolysaccharide. Since excessive tissue was voluminous in the BML, high-grade plasty techniques, such as combination of multiple resection and chordal reconstruction were required.

Abstract 18918: Distinct Gene Expression Profiles of the Mitral Valve Leaflets in Barlow’s Disease and Fibroelastic Defficiency

OBJECTIVES: The mitral valve (MV) leaflets in severe MR undergo structural remodeling associated with multiple degenerative and adaptive changes. We hypothesized that the gene expression profiles of the posterior MV leaflets from patients with bileaflet prolapse (Barlow’s valves) are distinct from those with only posterior leaflet degeneration (fibroelastic deficiency or MMR), reflecting different underlying pathophysiologic processes. Methods: MVs were obtained from 12 Barlow’s patients (9 m, 3 f; age= 59.8±12.2 y, LVEF=60.4±5.8%) and 17 MMR patients (10 m, 7 f, age= 54.2±6.6 y, LVEF=59.7±5.1%) undergoing surgery for severe MR. Normal MV were obtained from 6 unmatched donor hearts (4 m, 2 f, age= 41.5±10.7 y, LVEF=57.5±8.8%). RNA was extracted and cDNA microarray was carried on the Affymetrix Gene Chip 1.1. Normalization and two-way ANOVA analysis were performed. Only genes that resulted in &gt;1.5 fold difference and p &lt;0.05 were considered significantly altered. RESULTS: Of ~29,000 genes examined, 973 (3.3%) were differentially expressed between the two disease groups. Principal component analysis and Hierarchical clustering of the normalized fluorescence signal values for these genes successfully differentiated all the Barlow’s from the MMR samples (Figure 1). Based on functional analysis, selected statistically significant enriched biological processes are listed in (table1). Conclusions: MV leaflets in Barlow’s and MMR exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in the leaflet remodeling processes. Understanding such adaptive mechanisms can potentially provide therapeutic opportunities.

Interrupted Commissural Band Annuloplasty for Degenerative Mitral Valve Disease

Mitral annuloplasty is useful for treating degenerative mitral valve disease. Although the incidence of complications is low, prosthetic ring-related complications can occur. Hemolysis and mitral stenosis are serious complications requiring reoperation. Limited use of prosthetic material could decrease the risk for complications. Commissural annuloplasty has been reported by Kay and Reed; their techniques involve suture plication. To prevent dehiscence, we selected short bands and compared the echocardiographic changes between this method and the Cosgrove ring. Three sutures are placed in the commissures using two bands, which shortens the annular length by 60%. We performed this interrupted commissural band annuloplasty (iCBA) in 63 patients and used Cosgrove bands for 58 patients. Clinically, for iCBA and Cosgrove groups, respectively, hemolysis with mild mitral regurgitation occurred in 0 and 2 cases (p=0.084), and mitral stenosis due to pannus formation occurred in 0 and 1 case (p=0.224). There was a trend toward a lower ring-related complication rate in the iCBA group. On echocardiography, for the iCBA and Cosgrove groups, respectively, the maximum anterior-posterior distance of the annulus in diastole was 3.1±0.7 mm and 2.6±0.4 mm (p<0.001), maximum opening angle of the posterior leaflet was 85.7±17.3 degrees and 103.4±20.1 degrees (p<0.001), and coaptation distance was 11.6±3.7 mm and 8.4±2.6 mm (p<0.001). The iCBA method prevented posterior leaflet tethering, kept the coaptation distance deep on echocardiography, and was associated with lower trends of ring-related complications. Because the posterior side of the annulus was not reconstructed, iCBA is suitable for fibroelastic deficiency, rather than for Barlow's disease.