Myxomatous Valve Research Articles

Prevalence, risk factors and survival in dogs with myxomatous valve degeneration

ABSTRACT The objective of this study was to describe the prevalence, survival time, and risk factors of myxomatous mitral valve disease (MMVD) in dogs by a retrospective observational cohort study design of a Brazilian veterinary center, admitted from 2012 to 2018 (2.585 days). Considering the 105 dog files confirmed as MMVD, the prevalence of the disease was higher in small-breed dogs with ages from 10 to 19 years (30.3%). The survival time of the dogs at B1 stage (1.854 ± 145 days) was higher than the B2 (1.508+209) and C/D (930 ± 209). Higher risks of death (hazard ratio) were detected in the presence of syncope (2.5), pulmonary crackling (2.0), dyspnea (1.9), and higher values of vertebral heart scale (1.7), radiographic left atrium dimension (1.8), the ACVIM staging (1.7), and the duration of QRS complex (1.05). The results achieved demonstrated higher prevalence of MMVD in old small-breed dogs, associated with longer survival time in the B1 stage of the disease, and higher risk of death related to the presence of clinical signs, such as dyspnea, syncope, and pulmonary crackling, beyond some radiographic, echocardiographic, and electrocardiographic variables of heart or atrial enlargement.

Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease.

This paper is dedicated to the memory of Dr. Adriana “Adri” Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many aspects of heart development, including aspects of cardiac valve formation and disease and the role of the epicardium in the formation of the heart. In this contribution, we review some of the work on the role of epicardially-derived cells (EPDCs) in the development of the atrioventricular valves and their potential involvement in the pathogenesis of myxomatous valve disease (MVD). We provide an overview of critical events in the development of the atrioventricular junction, discuss the role of the epicardium in these events, and illustrate how interfering with molecular mechanisms that are involved in the epicardial-dependent formation of the atrioventricular junction leads to a number of abnormalities. These abnormalities include defects of the AV valves that resemble those observed in humans that suffer from MVD. The studies demonstrate the importance of the epicardium for the proper formation and maturation of the AV valves and show that the possibility of epicardial-associated developmental defects should be taken into consideration when determining the genetic origin and pathogenesis of MVD.

Pharmacological Inhibition of Macrophage Infiltration Prevents Myxomatous Valve Degeneration in Marfan Syndrome

Background Myxomatous valve degeneration (MVD) is the most common cause of mitral regurgitation, characterized by valve leaflet thickening and progressive valve degeneration, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome (MFS) is characterized leaflet thickening and increased macrophage infiltration which are reduced with loss of C-C chemokine receptor type 2 (CCR2). However, the specific contributions of macrophages to pathological extracellular matrix (ECM) remodeling and the underlying mechanisms are unknown. Methods Mice with the mutation of Fibrillin 1 (Fbn1C1039G/+) recapitulate histopathological features of MFS. ECM remodeling in mitral valves was assessed by detecting collagen and proteoglycan in Fbn1C1039G/+; CCR2RFP/RFP mice. Here, we tested the efficacy of a selective CCR2 antagonist RS504393 in the valves of MFS model in the initiation (1-month-old) and the progression (2-month-old) of MVD, respectively. MFS mice were intraperitoneally injected with RS504393 at 2 mg/kg/d for 1 month. Histological evaluation and immunofluorescence for macrophages and ECM were performed. Results MFS valves revealed ECM abnormalities characterized by collagen fragmentation and proteoglycan accumulation. Deficiency of CCR2 inhibited ECM abnormalities in MFS mitral valves. RS504393 treatment reduced infiltrating macrophages (MHCII+, CCR2+) in myxomatous valves. Remarkably, RS504393 was protective against both the initiation and the progression of MVD, detected by decreased mitral valve thickness and prevented pathological ECM remodeling in MFS mice. Conclusion Our results suggest the deficiency of CCR2 inhibits macrophage infiltration and abnormal ECM remodeling. In addition, the CCR2 inhbitor RS504393 is a potential pharmacological candidate to treat MVD in MFS.

Prox1+ Endothelial Cells in Heart Valve Development and Homeostasis

Heart valve malformations are commonly found in congenital heart defects and acquired valve disease affects 2.5% of the U.S. population. As blood circulates through the heart, the valves are subjected to fluid forces that potentially dictate the gene expression profile of their surface endothelial cells with implications for valve development and disease. Recently, three distinct valve endothelial cell (VEC) subpopulations were found to be localized to regions of unique blood flow patterns. However, the role of these subpopulations in heart valve development and disease is largely unknown. Prox1, an oscillatory shear stress (OSS)-sensitive regulator of lymphatic valves, is highly expressed in a VEC subpopulation exposed to OSS. In mouse heart valves, Prox1 is restricted to VECs on the fibrosa side of the aortic valve leaflet starting at embryonic day (E)12.5 and is maintained in adults. However, in myxomatous valve disease, commonly characterized by enlarged mitral and aortic valves and abnormal blood flow, Prox1 expression is expanded to both sides of the valve leaflets. Therefore, we hypothesize that Prox1 regulates heart valve leaflet elongation and size in response to blood flow. To determine the role of Prox1 in heart valves, we are analyzing heart valve morphogenesis and homeostasis in mice with embryonic VEC-specific Prox1 loss-of-function (Prox1 cKO). Preliminary studies using 3D reconstructions of Prox1 cKO hearts suggests that embryonic loss of Prox1 results in abnormal valve leaflets postnatally which become myxomatous in adulthood. Together, these data indicate an important role for Prox1 in heart valve development and disease.

The pathomechanism of human myxomatous valvular degeneration at the mechanical and cellular level.

The purpose of this study was to explore the pathomechanism of human myxomatous valve degeneration by investigating changes in the phenotype of valvular cells, the metabolism of the extracellular matrix and their mechanical properties. Mitral valve specimens were harvested from patients who had undergone valve replacement, and divided into two groups: patients with a myxomatous mitral valve and a control group. Histological investigation showed that the morphology of the extracellular matrix was looser and less coordinated in myxomatous valves than in controls. α-SMA (α-smooth muscle actin) and Vimentin were positive and DNA (deoxyribonucleic acid) assay of leaflets and expression of SMemb (embryonic smooth muscle myosin heavy chain), MMP-13 (matrix Metalloproteinases-13), MMP-1 mRNA (messenger Ribonucleic Acid) of the myxomatous valves were increased while the hydroxyproline content, expression of TIMP-1 (tissue inhibitor of metalloproteinase-1) mRNA and mechanical properties were decreased compared with controls. Compared to the quiescent interstitial cells in non-myxomatous valves, interstitial cells in myxomatous valves exhibit myofibroblast activation and express excessive levels of matrix metalloproteinases. The balance between MMP/TIMP was disrupted. We conclude that overactivation of VICs (Valvular interstitial cells) and the imbalance of MMP/TIMP could be important features of the pathomechanism of myxomatous mitral valve degeneration.

Preliminary Outcome of a Novel Edge-to-Edge Closure Device to Manage Mitral Regurgitation in Dogs.

Background: Veterinary management of mitral valve regurgitation due to mxyomatous valve disease in dogs is limited to medical treatments, which only postpones the onset of congestive heart failure or alleviates clinical symptoms. Most surgical procedures to manage this condition in humans require cardiopulmonary bypass and have a high risk of complications.Animals: Eight dogs with naturally occurring mitral valve regurgitation.Methods: Prospective observational study. All dogs were treated with a novel edge-to-edge transcatheter device named ValveClamp. The total surgical procedural time and total catheterization time were recorded. Echocardiographic variables measured pre- and post-procedure were compared using Wilcoxin-signed rank test with a P < 0.05 considered significant. Data were expressed as median and interquartile range and absolute numbers and percentages.Results: The procedural success rate was 100% and all the dogs survived without complications. The median (interquartile range) total surgical procedural time was 86.5 (76–96.2) minutes and catheterization time was 23.5 (22–33.8) minutes. Echocardiography revealed a significant reduction in mitral regurgitation severity in all dogs following the procedure based on both a reduced mitral regurgitant maximum jet area (P = 0.012) and a reduced mitral regurgitant maximum jet area to left atrial area (P = 0.018).Conclusion: The ValveClamp device is effective at reducing the severity of mitral regurgitation in dogs with naturally occurring myxomatous valve disease.

New insights into the pathophysiology of mitral valve disease: molecular characterisation and comparison of the different aetiologic subtypes

Abstract Introduction Mitral valve disease (MVD) is a frequent cause of heart failure and death. Data regarding its molecular basis are scarce, although current evidences show that primary MVD is an active process with the involvement of several molecular pathways. However, there are no studies that compare such mechanisms among the different subtypes of primary MVD. ST-2/interleukin (IL)-33 pathway is a potential pathophysiological mediator of cardiovascular diseases, although its role in heart valve diseases has not been explored. Purpose We aimed to analyse the molecular and cellular mechanisms involved in the main subtypes of primary chronic MVD: myxomatous degeneration, calcific or senile degeneration and rheumatic MVD. Methods 200 patients undergoing mitral valve replacement due to chronic primary MVD were enrolled. We classified them in the three main aetiologic subtypes according to echocardiographic features and surgeon's description: myxomatous degeneration (89 patients), senile or calcific degeneration (54 patients) and rheumatic disease (57 patients). In all patients the resected valve tissue and blood samples were collected. RT-PCR, Western Blot and ELISA were performed to analyse markers of inflammation (C-reactive protein, Rantes, IL-6, IL-1β/IL-1F2, tumor necrosis factor (TNF)-α), calcification (osteopontin, bone morphogenic protein (BMP)-2 and -4 and periostin), valvular endothelial cells (CD-31, E-cadherin), extracellular matrix remodeling (matrix metalloproteinase (MMP)-1, -2 and -9, tissue inhibitor of MMP-1 and -2), proteoglycans (aggrecan, hyaluronan, lumican, biglycan, syndecan-1, decorin) fibrosis (collagen-1, fibronectin, galectin-3, Transforming growth factor (TGF)-β) and ST-2/IL-33 system. Results Each aetiologic subtype showed a distinct marker profile. As compared with the other subtypes, myxomatous valves presented significantly higher levels of inflammatory markers (Rantes, IL-6), fibronectin, proteoglycans (hyaluronan, lumican and biglycan), ST-2 and IL-33. Senile degenerative valves presented significantly higher levels of calcification markers (osteopontin, BMP-2 and -4). Rheumatic valves were characterized by high levels of TNF-α and TGF-β compared to other subtypes and a significant increase in the expression and activity of matrix degradation enzymes (MMP-1 and -2). Conclusions Our study provides for the first time the molecular characterisation of the main aetiologic subtypes of chronic MVD. Proteoglycans accumulation, fibrosis and inflammation are the main features of myxomatous changes, whereas calcification define senile degeneration. Rheumatic valves exhibit elevated TNF-α and TGF-β and a dramatic increase in matrix turnover. Moreover, myxomatous valves overexpress the ST-2/IL-33 system, suggesting that this pathway could play a role in the development of myxomatous changes. Unravelling the underlying molecular mechanisms of each aetiology is essential to identify new therapeutic targets. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fondo de Investigaciones Sanitarias

Functional, structural and molecular characterization of a new mitral valve prolapse animal model: The FLNA-P637Q KI rat

Mitral Valve Prolapse (MVP) affects 3% of the population and is characterized by a heterogeneous mitral leaflet remodeling. The pathophysiological mechanisms involved in MVP development are not fully understood, the only therapeutic option remains the surgical valve replacement. The first mutation causing MVP has been recently identified on the FLNA gene. The generation of a unique knock-in (KI) rat model for the FLNA-P637Q mutation paves the road to study the molecular mechanisms involved in MVP development. The aim of our study was to characterize the functional, morphological and molecular expression of the valvular disease in our unique KI rat model. 5 wild-type (WT) and 10 KI rats were evaluated at 3, 6 and 26 weeks. Comprehensive 2D echocardiography was performed to determine valve function and morphology. 3D quantitative analysis of the mitral valve (MV) remodelling was done using micro-tomodensitometry (microCT). MV tissue composition was analysed based on histological and immunohistochemistry. Based on the qualitative echocardiographic assessment of the valve, a high genotype-phenotype concordance was observed (100%, 93% and 100% for each time points). The anterior leaflet was longer in KI comparatively to WT rats (+ 12 to + 14% increase at all time points P < 0.01). Using microCT analysis, we confirmed the larger 3D MV volume in KI compared to WT (+ 20 to + 58%; all time points P < 0.05). Histological and immunohistological analyses pointed out towards a myxomatous valve disease (leaflet's thickening, hypercellularity, proteoglycans accumulation without calcification). Our results attest for the presence of a myxomatous MV dystrophy in the KI rat model comparable to the one described in MVP patients. These findings confirm this unique model is pertinent for the study of pathophysiological molecular mechanisms associated with MVP development and offers a new opportunity to identify potential therapeutic targets.

Use of vertebral left atrial size for staging of dogs with myxomatous valve disease

Introduction/ObjectivesThe American College of Veterinary Internal Medicine (ACVIM) guidelines suggest that pimobendan should be initiated in dogs which meet all criteria of stage B2 myxomatous mitral valve disease (MMVD): murmur intensity ≥ 3/6, left atrial-to-aortic ratio ≥ 1.6, normalized left ventricular internal diameter in diastole ≥ 1.7, and vertebral heart size > 10.5. Recently, a new radiographic index for left atrial enlargement, vertebral left atrial size (VLAS), was proposed. The objective of the present study was to evaluate whether VLAS is useful in staging MMVD and if it can distinguish between ACVIM stages B1 and B2. AnimalsNinety-seven client-owned dogs with MMVD were evaluated and classified as ACVIM stage B1, B2, or C-D. Materials and MethodsThe echocardiographs and radiographs of all the dogs were retrospectively evaluated to obtain left atrial-to-aortic ratio, normalized left ventricular internal diameter in diastole, and VLAS values. The data were analyzed to assess the correlation between these measurements and VLAS, and the optimal cutoff value of VLAS was determined. ResultsA VLAS cutoff value of 2.6 provided the greatest diagnostic accuracy for identification of dogs with ACVIM stage B2 MMVD (area under the curve, 0.96; sensitivity, 95%; specificity, 84%). A VLAS ≥2.5 exhibited the highest sensitivity (sensitivity, 100%; specificity, 78%), and a VLAS ≥ 3.1 exhibited the highest specificity (sensitivity, 47%; specificity, 100%). ConclusionsVLAS is a helpful index for monitoring MMVD using radiography. A VLAS cutoff value of 2.5 could be used to identify dogs that may benefit from echocardiography to determine if they have reached ACVIM stage B2.

Echocardiographic Evaluation of Right Ventricular Function Using Two-Dimensional Echocardiographic Measurements and Pulsed Wave Doppler Ultrasound in Dogs with Myxomatous Valve Disease and Measurable Tricuspid Regurgitation

Echocardiographic Evaluation of Right Ventricular Function Using Two-Dimensional Echocardiographic Measurements and Pulsed Wave Doppler Ultrasound in Dogs with Myxomatous Valve Disease and Measurable Tricuspid Regurgitation

Macrophage lineages in heart valve development and disease.

Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from haematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that haematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here, we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications.

A single nucleotide deletion resulting in a frameshift in exon 4 of TAB2 is associated with a polyvalular syndrome

Polyvalvularmyxomatous degeneration is a rare clinical condition. A 51-year-old male patient presented at our centre with all four heart valves with myxomatous degeneration and severe mitral and aortic regurgitation due to leaflet prolapse. The patient referred five further family members with valvular heart disease at different stages of presentation. The aim of this study was to investigate the genetic basis of this familial polyvalvularmyxomatous degeneration which was associated with mild dysmorphic facial anomalies and short stature. A detailed family history was recorded. Nine members of the family, affected or not by valvular heart disease, were studied clinically, echocardiographically and by detailed genetic analyses. Six of the nine family members had echocardiographic features of different degrees of degenerative heart valve disease. In addition, the affected subjects shared similar mild dysmorphic facial anomalies and short stature. Exome sequencing identified a rare heterozygous single nucleotide deletion in the TAB2 gene in all affected family members, which was absent in the unaffected members. A variant in the TAB2 gene is proposed as the cause of syndromic congenital heart disease, displaying congenital myxomatous degenerative heart valve disease, mild dysmorphic fascial anomalies and short stature in this family.

Deficiency of Circulating Monocytes Ameliorates the Progression of Myxomatous Valve Degeneration in Marfan Syndrome.

Myxomatous valve degeneration (MVD) involves the progressive thickening and degeneration of the heart valves, leading to valve prolapse, regurgitant blood flow, and impaired cardiac function. Leukocytes composed primarily of macrophages have recently been detected in myxomatous valves, but the timing of the presence and the contributions of these cells in MVD progression are not known. We examined MVD progression, macrophages, and the valve microenvironment in the context of Marfan syndrome (MFS) using mitral valves from MFS mice (Fbn1C1039G/+), gene-edited MFS pigs (FBN1Glu433AsnfsX98/+), and patients with MFS. Additional histological and transcriptomic evaluation was performed by using nonsyndromic human and canine myxomatous valves, respectively. Macrophage ontogeny was determined using MFS mice transplanted with mTomato+ bone marrow or MFS mice harboring RFP (red fluorescent protein)-tagged C-C chemokine receptor type 2 (CCR2) monocytes. Mice deficient in recruited macrophages (Fbn1C1039G/+;Ccr2RFP/RFP) were generated to determine the requirements of recruited macrophages to MVD progression. MFS mice recapitulated histopathological features of myxomatous valve disease by 2 months of age, including mitral valve thickening, increased leaflet cellularity, and extracellular matrix abnormalities characterized by proteoglycan accumulation and collagen fragmentation. Diseased mitral valves of MFS mice concurrently exhibited a marked increase of infiltrating (MHCII+, CCR2+) and resident macrophages (CD206+, CCR2-), along with increased chemokine activity and inflammatory extracellular matrix modification. Likewise, mitral valve specimens obtained from gene-edited MFS pigs and human patients with MFS exhibited increased monocytes and macrophages (CD14+, CD64+, CD68+, CD163+) detected by immunofluorescence. In addition, comparative transcriptomic evaluation of both genetic (MFS mice) and acquired forms of MVD (humans and dogs) unveiled a shared upregulated inflammatory response in diseased valves. Remarkably, the deficiency of monocytes was protective against MVD progression, resulting in a significant reduction of MHCII macrophages, minimal leaflet thickening, and preserved mitral valve integrity. All together, our results suggest sterile inflammation as a novel paradigm to disease progression, and we identify, for the first time, monocytes as a viable candidate for targeted therapy in MVD.

8p23.1 Microdeletion syndrome and obstructing myxomatous heart valve nodules.

8p23.1 Microdeletion syndrome and obstructing myxomatous heart valve nodules.

1641 Bicuspid pulmonary valve - an unusual cause of dilated pulmonary artery

Abstract Introduction Dilated pulmonary artery is a common finding with a variety of possible aetiologies. We present a case of unexplained dilated pulmonary artery that was associated with bicuspid pulmonary valve identified by CMR. Case Presentation A 67-year-old female underwent mitral valve repair for severe mitral regurgitation. She had presented with breathlessness, and had severe mitral regurgitation due to a myxomatous valve with bileaflet prolapse, confirmed with TOE. Echo showed: normal LV dimensions, LVEF 66%. RV size and systolic function normal. Coronary angiography was normal and pulmonary hypertension was not present on right heart catheterization. At postoperative follow up she was well and asymptomatic, with echo showing good LV systolic function, intact mitral valve repair, and normal systolic pulmonary artery pressures (36mmHg). New T wave inversion was identified across the precordial leads so a CMR was performed. CMR showed normal LV volumes and function with no wall motion abnormality or LVH. There was no fibrosis or infarction in the late phase after Gadolinium contrast. The RV was dilated (73mm diameter at base) with normal systolic function. The main pulmonary artery was dilated at 42mm. Flow mapping showed no evidence of shunt (Qp:Qs = 1:1) and the atrial septum was intact. Pulmonary valve function was normal but the valve was bicuspid in morphology. Discussion Bicuspid pulmonary valve is a rare finding. In our case this was identified by CMR and was associated with a dilated pulmonary artery. Bicuspid pulmonary valve is most commonly identified in the context of pulmonary valve stenosis. Isolated pulmonary valve stenosis is a rare finding; it is most often associated with other congenital defects like Fallot. Pulmonary stenosis has been associated with pulmonary artery aneurysm, attributed to hemodynamic changes caused by the stenotic valve. However as with bicuspid aortic valve it is recognized that the "post stenotic dilation" is part of the pathology of bicuspid valve and does not need the changed haemodynamics of a stenotic valve. During embryogenesis neural crest cells are necessary for the normal development of the semilunar valves, the septation of the outflow tract into the aorta and pulmonary artery, and the remodeling of the aortic arch. Any defect in this migration can cause abnormalities or aneurysm of the aorta or pulmonary artery together with semilunar valve defects. A study of 3,861 donor hearts dissected at the European Homograft Bank revealed only four cases (0.1%) of bicuspid pulmonary valves. Bicuspid pulmonary valve with normal function can be difficult to identify at echocardiography. It can be well visualized by CMR and this can be combined with an assessment of the pulmonary arteries. It should be remembered as a rarer cause of dilated pulmonary artery when other causes have been excluded. Figure A. Dilated MPA. B. Dilated RV. C. and D. Bicuspid pulmonary valve. Abstract 1641 Figure. Dilated MPA. Bicuspid pulmonary valve

SUDDEN CARDIAC DEATH ASSOCIATED WITH MALIGNANT MITRAL VALVE PROLAPSE

Mitral Valve Prolapse (MVP) is caused by myxomatous valve leaflet changes. Malignant MVP is an understated cause of sudden cardiac death (SCD). A 56 year old female A with history of MVP presented as a witnessed cardiac arrest while golfing. Patient received bystander CPR and was defibrillated once

The Frequency and Outcomes of Limited-Access Valve, All-Arterial Graft, and Off-Pump Coronary Surgery in Australia

Aim: This presentation details the frequency of use and outcomes of limited access valve surgery, all arterial and off-pump coronary grafting, and mitral valve repair for myxomatous valve disease versus more traditional methods.

Endothelial Cell Lineage Analysis Does Not Provide Evidence for EMT in Adult Valve Homeostasis and Disease.

Epithelial-to-mesenchymal transition (EMT) enables stationary epithelial cells to exhibit migratory behavior and is the key step that initiates heart valve development. Recent studies suggest that EMT is reactivated in the pathogenesis of myxomatous valve disease (MVD), a condition that involves the progressive degeneration and thickening of valve leaflets. These studies have been limited to in vitro experimentation and reliance on histologic costaining of epithelial and mesenchymal markers as evidence of EMT in mouse and sheep models of valve disease. However, longitudinal analysis of cell lineage origins and potential pathogenic or reparative contributions of newly generated mesenchymal cells have not been reported previously. In this study, a genetic lineage tracing strategy was pursued by irreversibly labeling valve endothelial cells in the Osteogenesis imperfecta and Marfan syndrome mouse models to determine whether they undergo EMT during valve disease. Tie2-CreER T2 and Cdh5(PAC)-CreER T2 mouse lines were used in combination with colorimetric and fluorescent reporters for longitudinal assessment of endothelial cells. These lineage tracing experiments showed no evidence of EMT during adult valve homeostasis or valve pathogenesis. Additionally, CD31 and smooth muscle α-actin (αSMA) double-positive cells, used as an indicator of EMT, were not detected, and levels of EMT transcription factors were not altered. Interestingly, contrary to the endothelial cell-specific Cdh5(PAC)-CreER T2 driver line, Tie2-CreER T2 lineage-derived cells in diseased heart valves also included CD45+ leukocytes. Altogether, our data indicate that EMT is not a feature of valve homeostasis and disease but that increased immune cells may contribute to MVD. Anat Rec, 302:125-135, 2019. © 2018 Wiley Periodicals, Inc.

Valve repair to avoid prosthetic valve pathology: Mid-term results in mitral valve repair.

In this study, we aimed to present our results of mitral valve repair. Between January 2007 and November 2016, a total of 128 patients (72 males, 56 females; mean age 51.8±17.2 years; range 16 to 84 years) who underwent mitral valve repair in our heart center were retrospectively analyzed. There were mitral regurgitation in 86.7% (n=111), mitral stenosis in 7.8% (n=10), and mixed type valve disease in 5.5% of the patients (n=7). Mitral ring annuloplasty was performed in 80.5% (n=103), implantation of the artificial chordae in 36.7% (n=47), open mitral commissurotomy in 13.3% (n=17), and Alfieri procedure in 6.3% (n=8) of the patients. Sixty-two patients (48.8%) underwent isolated mitral valve repair, while concomitant surgical procedures were performed in the remaining patients. Postoperative mean follow-up was 52 months. Early (30-day) mortality was observed in seven patients due to low cardiac output. There was no mid-term mortality. During follow-up, various degree of mitral regurgitation was detected in 4 patients (3.6%), regurgitation was severe in two of them and these two require reoperation with the replacement of the valve. Patients with a myxomatous valve pathology who underwent isolated valve repair most benefited from valve repair. Patients with isolated mitral stenosis were the most successful group among the patients with a rheumatic etiology. Postoperative echocardiography showed a significant decrease in the left atrial diameter and pulmonary artery systolic pressures (p<0.01). Mitral valve repair can be applied as an effective and safe treatment method in patients in whom the mitral valve anatomy is sufficient for repair. We suggest that each patient with mitral valve pathology should be evaluated in terms of reparability.

Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease

Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing and contribution of macrophages in normal valves and myxomatous valve disease are still unknown. The objective is to characterize leukocytes during postnatal heart valve maturation and identify macrophage subsets in myxomatous valve disease. Leukocytes are detected in heart valves after birth, and their numbers increase during postnatal valve development. Flow cytometry and immunostaining analysis indicate that almost all valve leukocytes are myeloid cells, consisting of at least 2 differentially localized macrophage subsets and dendritic cells. Beginning a week after birth, increased numbers of CCR2+ (C-C chemokine receptor type 2) macrophages are present, consistent with infiltrating populations of monocytes, and macrophages are localized in regions of biomechanical stress in the valve leaflets. Valve leukocytes maintain expression of CD (cluster of differentiation) 45 and do not contribute to significant numbers of endothelial or interstitial cells. Macrophage lineages were examined in aortic and mitral valves of Axin2 KO (knockout) mice that exhibit myxomatous features. Infiltrating CCR2+ monocytes and expansion of CD206-expressing macrophages are localized in regions where modified heavy chain hyaluronan is observed in myxomatous valve leaflets. Similar colocalization of modified hyaluronan and increased numbers of macrophages were observed in human myxomatous valve disease. Our study demonstrates the heterogeneity of myeloid cells in heart valves and highlights an alteration of macrophage subpopulations, notably an increased presence of infiltrating CCR2+ monocytes and CD206+ macrophages, in myxomatous valve disease.