The clinical features in six patients with mitral insufficiency due to chordae tendineae have been. The patients in whom the etiology was not known did not become symptomatic till they were past 40, although a murmur had been present for several years. Pulmonary edema or paroxysmal nocturnal dyspnea were the initial symptoms in a number of these patients, preceding the more usual shortness of breath with exertion. The auscultatory and phonocardiographic features are specific. On fluoroscopy readily recognizable paradoxical pulsation of the left atrium was present in some of them. At cardiac catheterization a tall left atrial “v” wave with peak pressure as high as or higher than the peak pressure in the pulmonary artery was constantly found. In a patient with mitral insufficiency where the murmur is harsh and accompanied by a thrill in the fourth intercostal space near the left sternal border and in whom an ejection type systolic murmur is heard unaccompanied by the slow rising pulse of aortic stenosis, the possibility of mitral insufficiency due to ruptured chordae tendineae should be considered.

No description available.

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 31 min and cardiopulmonary bypass was 137 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This “off label” implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

Currarino-Silverman syndrome is a rare disorder characterized by premature fusion of manubrio-sternal joint and the sternal segments, resulting in a high carinate chest deformity; it is frequently associated with congenital heart disease. Among the various heart lesions reported in this syndrome, mitral valve disease and coarctation of the aorta have not yet been described (to our knowledge). Our report consists of five children with this syndrome, four of whom had mitral valve disease, with an associated coarctation of the aorta in one patient. The fifth patient had an innocent heart murmur.

Η πρωτεΐνη YKL-40 είναι μια εκκρινόμενη πρωτεΐνη, μέλος της οικογένειας των γλυκοπρωτεϊνών που ομοιάζουν με χιτινάση. Περιέχει καλά συντηρημένες περιοχές που προσδένουν χιτίνη, στερείται όμως της ενζυματικής δράσης της χιτινάσης εξαιτίας μιας σημειακής μετάλλαξης στην καταλυτική περιοχή. Από την υπάρχουσα βιβλιογραφία φαίνεται να εμπλέκεται στη διαδικασία της φλεγμονής αλλά και στη δημιουργία ίνωσης και νεοαγγειογένεσης. Στην παρούσα μελέτη, θελήσαμε να διερευνήσουμε την έκφραση της YKL-40 με την τεχνική της ανοσοιστοχημείας σε μιτροειδείς βαλβίδες του ανθρώπου με ιστοπαθολογικές αλλοιώσεις ( βλεννώδη εκφύλιση ,ινωση ,νεοαγγειογένεση ασβέστωση ) και να συσχετίσουμε την πιθανή έκφραση της πρωτεϊνης με την παρουσία και την σοβαρότητα αυτών των αλλοιώσεων καθώς και με άλλες κλινικοπαθολογοανατομικές παραμέτρους της νόσου Χρησιμοποιήθηκαν συνολικά δείγματα από 71 περιστατικά μιτροειδών βαλβίδων μονιμοποιημένα σε ουδέτερη φορμόλη 10% και εγκλεισμένα σε παραφίνη. Εκ των οποίων τα 52 ήταν παθολογικά και τα 19 ήταν φυσιολογικά. Εφαρμόσθηκε η τεχνική της ανοσοιστοχημείας και τα αντισώματα YKL-40, VEGFA, CD31, CD68 και A-SMA. Η στατιστική ανάλυση των αποτελεσμάτων έγινε με τη χρήση του στατιστικού πακέτου SPSS 10.0 for Windows. Τα αποτελέσματα της μελέτης έδειξαν ότι η πρωτεΐνη YKL-40 υπερεκφράζεται στις παθολογικές βαλβίδες (στα μακροφάγα, στα ενδοθηλιακά και στα διάμεσα βαλβιδικά κύτταρ ) και ότι τα υψηλά επίπεδα έκφρασης της σχετίζονται με τη σοβαρότητα των ιστοπαθολογικών αλλοιώσεων. Μόνο σε 2 από τις 19 φυσιολογικές βαλβίδες παρατηρήθηκε θετική ανοσοϊστοχημική χρώση, στις υπόλοιπες 17 ήταν αρνητική. Η ανοσοϊστοχημική χρώση της πρωτεΐνης YKL-40 στις μιτροειδείς βαλβίδες είχε στατιστικά σημαντική σχέση με την ανοσοϊστοχημική έκφραση της πρωτεΐνης A-SMA, της πρωτεΐνης VEGFA, με την παρουσία μακροφάγων και την μέση αγγειακή πυκνότητα.Τα επίπεδα έκφρασης της πρωτεΐνης YKL-40 ήταν μεγαλύτερα στις γυναίκες με νόσο μιτροειδούς βαλβίδας και σχετίζονται στατιστικά σημαντικά με την ηλικία. Με βάση τα ανωτέρω αποτελέσματα, μπορούμε να εισηγηθούμε ένα πιθανό ρόλο της πρωτεΐνης YKL-40 στην παθογένεια της νόσου της μιτροειδούς βαλβίδας , καθώς φάνηκε να εκφράζεται από διάφορους κυτταρικούς τύπους στις παθολογικές βαλβίδες σε σχέση με τις φυσιολογικές όπου δεν παρατηρήθηκε ανοσοθετικότητα του μορίου. Η έκφραση της πρωτεΐνης YKL-40 είχε θετική συσχέτιση με την έκφραση της a-SMA στα διάμεσα κύτταρα της βαλβίδας γεγονός που πιθανολογεί το ενδεχόμενο η πρωτεϊνη YKL-40 να προκαλεί ενεργοποίηση των διάμεσων βαλβιδικών κυττάρων με αποτέλεσμα την παραγωγή πρωτεϊνών εξωκυτταρίου ουσίας με τελική κατάληξη τη δημιουργία βλεννώδους εκφύλισης και ίνωσης . Επιπροσθέτως θα μπορούσαμε να υποθέσουμε λογω της θετικής συσχέτισης της έκφρασης της πρωτεΐνης YKL-40 με την έκφραση του VEGFA από τα βαλβιδικα κύτταρα και τα μακροφαγα ότι η πρωτεΐνη YKL-40 πιθανόν να επάγει την έκφραση του VEGFA από τα κύτταρα αυτά. Επιπρόσθετα, όπως η υπάρχουσα βιβλιογραφία υποστηρίζει, τόσο ξεχωριστά όσο και συνεργικά ο VEGFA και η YKL-40 είναι δυνατον να προκαλούν ενεργοποίηση, χημειοταξία και μετανάστευση ενδοθηλιακών κυττάρων εντός της γλωχίνας και σχηματισμό νέων αγγείων. Τα νέα αυτά αγγεία θα μπορούσαν να λειτουργήσουν θετικά ως προς την φλεγμονώδη διαδικασία προσκομίζοντας στις ήδη παχυσμένες βαλβίδες θρεπτικά συστατικά καθώς και μόρια και κύτταρα του ανοσοποιητικού συστήματος. Η παρουσία των μακροφάγων στις παθολογικές βαλβίδες φαίνεται να παίζει κεντρικό ρόλο στην ανάπτυξη των φλεγμονωδών αλλοιώσεων. Η στατιστικά σημαντική σχέση των μακροφάγων με την πρωτεΐνη YKL-40, σε συνδυασμό με την υπάρχουσα βιβλιογραφία που υποστηρίζει τόσο την έκκριση της πρωτεΐνης από τα μακροφάγα, όσο και την επίδραση της σε αυτά, μας επιτρέπει να υποθέσουμε και ένα παρόμοιο μηχανισμό στη νόσο της μιτροειδούς βαλβίδας. Αν και τα αποτελεσματα της παρουσας μελέτης είναι ενδεικτικά πιθανης συμμετοχής της YKL-40 στην νόσο της μιτροειδούς βαλβίδας χρειάζονται πολύ περισσοτερες μελέτες για να αποσαφηνισθεί ο ακριβής ρόλος της πρωτεΐνης YKL-40 στη παθογενεια της συγκεκριμένης νόσου / The protein YKL-40 is a secreted protein, a member of the family of chitinase-like glycoprotein. The protein YKL-40 contains well conserved regions that bind chitin, but lacks the enzymatic chitinase activity, because of a point mutation in the catalytic region. From the existing scientific literature it seems to be involved in the immigration and macrophage activation process in the site of inflammation. It is also possible to participate in the process of neoangiogenesis and fibrosis. Scientists argue that the protein YKL-40 participates in many diseases which are characterized by development of inflammation and has been proposed to use the protein YKL-40 as an indicator of prognosis, recurrence and treatment response in serum of patients with inflammatory diseases and malignancies. In this study, as the disease of the mitral valve is characterized by development of inflammation and because of existing studies that suggest that the protein YKL-40 induces the expression of VEGF-A protein and also has angiogenetic activity itself, we wanted to investigate the possible positive immunohistochemical staining of protein YKL-40 comparing physiological and pathological histological sections of mitral valve. A total sample of 71 cases was used. The 19 of them were normal and the 52 had lesions. The material was fixed tissue samples in 10% neutral formalin and embedded in paraffin. The 36 came from autopsy material and the remaining 35 of mitral valve replacement surgery. The kind of methodology that was followed was the indirect immunohistochemical method of streptavidin-DAB. The antibodies used were against the protein YKL-40, VEGF-A, CD31 (vascular endothelium), CD68 (macrophages) and A-SMA (activated valve interstitial cells). The statistical analysis was performed using the statistical package SPSS 10.0 for Windows. The study gave the following results: The protein YKL-40 is overexpressed in the pathological valves and its levels was related to the severity of the lesions. Cytoplasmic immunopositivity was present in macrophages, endothelial cells of the outer layers of the valves and the valves’ vessels and valve interstitial cells. Only 2 of the 19 normal valves had positive immunohistochemical stain of the protein YKL-40. Sufficient number of CD68 -positive macrophage was observed in the valves which presented histopathological lesions. The number of macrophages was significantly correlated with the severity of lesions. It was demonstrated the presence of vessels in pathological valves by immunohistochemical staining against the protein CD31. The average microvessel density was correlated with the severity of histological lesions. Pathological valves observed strong immunohistochemical expression of the protein A-SMA in the cells of the matrix. The expression of protein A-SMA was correlated significantly with the severity of lesions. The VEGF-A protein was overexpressed in pathological valves and was related to the severity of histopathological lesions. The cells which had positive immunostaining for the VEGF-A protein were macrophages, endothelial cells of valve blood vessels and valve interstitial cells. Immunohistochemical staining of the protein YKL-40 in the mitral valve was statistically significant compared to the immunohistochemical expression of the protein A-SMA, the protein VEGF-A, with the presence of macrophages and average microvessel density. The expression levels of the protein YKL-40 was higher in women with mitral valve disease and significantly associated with age. According to the previous comments, we propose the possible role of the protein YKL-40 in the pathogenesis of mitral valve disease. The protein YKL-40 seems to be expressed from multiple cellular types in pathological valves. As a different, the normal valves had non immunopositivity of the molecule. The YKL-40 protein was immunohistochemical localization in cells with morphological characteristics similar to those that were stained positive for a-SMA. Therefore, there is possibility that the presence of the protein YKL-40 in the valve interstitial cells is associated with increased cellularity of diseased valves, via the possible increase of the proliferation and activation of valve interstitial cells. As a result, the produce of ECM proteins causes mucous degeneration and fibrosis. Additionally we will assume that the protein YKL-40 is likely to induce the expression of VEGF-A from valve interstitial cells and/or macrophages during the pathogenesis of mitral valve disease. As the present bibliography consider, both separately and synergistically the protein YKL-40 is able to cause activation, chemo taxis and migration of endothelial cells within the cusp and neovascularization. These new vessels could operate positively to the inflammatory process by providing the thickened valves nutrients and molecules and cells of the immune system. The presence of macrophages at the valve lesions seems to play a major role at the inflammation procedure. Both of the statistically significant colleration between macrophages and protein YKL_40 and the current bibliography that suggests the expression of the protein YKL-40 from macrophages and the effect of the protein on them, make us to hypothesize that there is a similar mechanism at the mitral valve disease to. More research is required in order to make clear the exact role of protein YKL-40 in the mitral valve disease.

In der vorliegenden Studie wurden die prä- und postoperativen transthorakalen echokardiographischen Untersuchungen von 31 Patienten mit Mitralklappenrekonstruktion im Zeitraum von 2007 bis 2011 retrospektiv analysiert. Es wurden die Untersuchungen eingeschlossen, bei denen sowohl vor als auch nach dem operativen Eingriff das Bilddatenmaterial komplett zur Verfügung stand. Die echokardiographische Dokumentation der im klinischen Alltag durchgeführten Untersuchungen ermöglichte die Evaluation der Dimensionen von rechten und linken Ventrikel sowie beider Vorhöfe, der systolischen und diastolischen linksventrikulären Funktion, der Morphologie der Herzklappen sowie der pulmonalarteriellen Drücke. Die Patientenkohorte wurde zusätzlich in Subgruppen nach Symptomatik, nach additiven chirurgischen Interventionen und nach dem Vorliegen von chronischem Vorhofflimmern analysiert. Die Ergebnisse der Mitralklappenrekonstruktion zeigten erwartungsgemäß postoperativ eine signifikante Reduktion des Schweregrades der Mitralklappenregurgitation, eine Verkleinerung der linksseitigen Herzhöhlen, eine Normalisierung der linksventrikulären Pumpfunktion und der pulmonalarteriellen Drücke. Asymptomatische Patienten im Sinusrhythmus mit isolierter Mitralklappenrekonstruktion hatten die günstigsten postoperativen echokardiographischen Ergebnisse. Weiterhin war eine postoperativ eingeschränkte rechtsventrikuläre und linksventrikuläre diastolische Funktion zu postulieren. Ein mit fast 20% beträchtlicher Anteil der Patienten mit einer postoperativen Vena contracta der Mitralklappenregurgitation ≥ 3mm war vermutlich auf eine Vorselektion der Patienten zurückzuführen. Schlussfolgernd sollte eine Mitralklappenrekonstruktion möglichst vor Eintreten irreversibler kardialer Schädigungen durchgeführt werden.

Introdução e Objetivo: A doença mixomatosa da valva mitral leva ao comprometimento de sua matriz devido à alteração em sua composição tecidual provocada pelo desequilíbrio na quantidade de ácidos mucopolissacarídeos ou glicosaminoglicanos. Sua etiologia ainda não está totalmente esclarecida, podendo ocorrer em formas familiares com transmissão autossômica dominante de penetrância variável, que pode ser dependente do tempo ou de prováveis fatores ambientais, situações em que a interação de agentes infecciosos necessita de maiores esclarecimentos. O objetivo deste estudo é a análise dos produtos dos patógenos da Chlamydophila pneumoniae, Mycoplasma pneumoniae e Borrelia burgdorferi em segmentos de cúspide retirados da valva mitral com degeneração mixomatosa, comparada ao grupo controle e a relação dos produtos bacterianos com aumento de marcadores inflamatórios (CD20, CD48, CD68) e de metaloproteinase (MMP9) na etiopatogenia da degeneração mixomatosa da valva mitral. Método: Estudo observacional, analítico, tipo caso-controle, que analisou 2 grupos contendo 20 pacientes cada e divididos em grupo 1, composto por fragmentos de tecido valvar mitral com diagnóstico de degeneração mixomatosa extraídos em procedimentos de troca ou plásticas valvares mitrais; e grupo 2, formado por segmentos de valvas mitrais sem valvopatia retirados no serviço de verificação de óbito. Foram realizadas colorações de hematoxilina e eosina e Movat para diagnóstico histológico da degeneração mixomatosa e técnica de imunohistoquímica para detecção de antígenos da Borrelia burgdorferi, Mycoplasma pneumoniae, mediadores inflamatórios (CD20, CD45, CD68) e marcadores de metaloproteinase (MMP9). A presença de antígenos da Chlamydophila pneumonia e foi pesquisada pela técnica de hibridização in situ. A análise quantitativa dos aspectos microscópicos foi realizada com o analisador de imagens Aperio. A pesquisa de elementos bacterianos foi feita através de microscopia eletrônica de transmissão. Resultados: No grupo 1, 14 (70%) pacientes são do gênero masculino e 6 (30%) do gênero feminino. A idade média é de 67,4 anos (51 a 79 anos, dp = 9,2). No grupo 2, 11 (55%) pacientes são do gênero masculino e 9 (45%) do gênero feminino. A idade média é de 67,6 anos (42 a 84 anos, dp= 12,0). Na análise da porcentagem de degeneração mixomatosa pela coloração Movat, houve diferença com significância estatística entre os grupos DM (G1), com média de 54,6 % ± 23,7 e grupo controle (G2) com média de 35,5 % ± 22,5 com valor de p = 0,013. Houve um maior número de células CD20 positivas/mm2 no grupo com DM com mediana igual a 17,8 (6,7 - 27,9) x 4,6 (3,6 - 9,8) com p = 0,007 para a área 1. Houve maior número de células CD45 positivas/mm2 no grupo com DM com mediana igual a 17,3 (3,4 - 92,5) x 2,8 (1,4 - 10,1) com p = 0,008 para a área 1. Houve maior número de células CD68 positivas/mm2 no grupo controle (G2), porém sem significância estatística com mediana igual a 38,7 (26,6 - 81,8) x 70 (42,7 - 120,4) com p = 0,098 para a área 1. Em relação à presença de antígenos de Mycoplasma pneumoniae, houve uma maior área (?m2) de antígenos detectados no grupo 1, quando comparadas com o grupo 2 com diferença estatisticamente significante para as duas áreas. Na área 1, mediana de 180.993 (24.856 - 387.477) x 7.970 (2.736 - 15.992) com p < 0,001 e na área 2, mediana igual a 105.968 (2.503 - 416.585) x 7.190 (3.314 - 17.833) com p = 0,02 A análise da presença de antígenos de Chlamydophila pneumoniae demonstrou que em ambas as áreas, houve uma maior área (?m2) de antígenos detectados no grupo de valvas com degeneração mixomatosa, quando comparadas com o grupo controle, porém sem diferença estatística com mediana para o G1 de 9.905 (4.716 - 16.912) x 5.864 (2.382 - 8.692) com p = 0,2 e para o G2, mediana de 3.199 (1.791 - 10.746) x 2.536 (683 - 6.125) com p = 0,3. Em relação à presença de antígenos de Borrelia burgdorferi, houve uma maior área (um2) de antígenos detectados no grupo 2 em relação ao grupo 1, em ambas as áreas. Na área 1, mediana de 7.596 (3.203 - 13.519) x 10.584 (7.223 - 15.974) com p = 0,14 e na área 2, mediana igual a 5.991 (3.009 - 8.475) x 8.403 (1.626 - 27.887) com p = 0,47. Em relação à presença da metaloproteinase MMP9, observamos maior área (um2) de antígeno marcado de MMP9 no grupo com degeneração mixomatosa tanto na área 1 quanto na área 2, com diferença estatística significante. Na área 1, mediana de 503.894 (202.428 - 938.072) x 269.244 (111.953 - 354.022) com p = 0,03. Na área 2, houve diferença estatística representada pela mediana de 389.844 (214.459 - 679.711) x 144.397 (29.894 - 247.453) com p < 0,001. No grupo DM houve correlação positiva entre Borrelia burgdorferi e porcentagem de DM com R = 0,52 e p = 0,018. Em relação às células inflamatórias, houve correlação positiva entre CD45 e Mycoplasma pneumoniae com R = 0,51 e p = 0,02. A presença de MMP9 se correlacionou positivamente com a presença de Mycoplasma pneumoniae com R = 0,45 e p = 0,04. Estas correlações estiveram ausentes no grupo controle. Conclusões: Houve associação de agentes infecciosos Mycoplasma pneumoniae e Borrelia burgdorferi na etiopatiopatogenia da degeneração mixomatosa da valva mitral. Na análise da relação dos produtos bacterianos com os marcadores inflamatórios e com a metaloproteinase, houve relação positiva entre o marcador inflamatório CD45 e a metaloproteinase (MMP9) apenas com a Mycoplasma pneumoniae, nas valvas com degeneração mixomatosa. O marcador inflamatório CD68 foi encontrado em maior número no grupo controle / Background: The myxomatous mitral valve disease leads to impairment due to changes in their tissue composition caused by the imbalance in the amount of acid mucopolysaccharides or glycosaminoglycans. Its etiology is not yet fully understood and may occur in familial forms of autosomal dominant trait with variable penetrance that can be time-dependent or probable environmental factors, where the interaction of infectious agents requires further elucidation. The purpose of this study is the analysis of the pathogens products of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi in removed cusp segments of the mitral valve with myxoid degeneration, compared to the control group and the ratio of bacterial products with increased inflammatory markers (CD20, CD48, CD68) and metalloproteinase (MMP9) in the pathogenesis of myxomatous degeneration of the mitral valve. Method: Observational, analytical, case-control study which analyzed 2 groups of 20 patients each and divided in group 1, consisting of fragments of mitral valve tissue with diagnosis of myxomatous degeneration extracted in replacement procedures or mitral valve repair; group 2, formed by segments of mitral valves without valvolpaty clinial disease removed in the coroner service. Hematoxylin and eosin and Movat stains were done for histological diagnosis of myxoid degeneration and immunohistochemical technique for the detection of Borrelia burgdorferi, Mycoplasma pneumonia antigens, inflammatory mediators (CD20, CD45, CD68) and markers of metalloproteinase (MMP9). The presence of Chlamydophila pneumonia antigens was verified through an in situ hybridization technique. The quantitative analysis of the microscopic aspects was performed with the Aperio image analyzer. The research of bacterial elements was performed by a transmission electron microscopy. Results: In group 1, 14 (70%) patients were male and 6 (30%) were female. The mean age was (51 to 79 years, sd = 9.2). In group 2, 11 (55%) patients were male gender and 9 (45%) were female. The mean age was 67,6 years (42 to 84 years, sd= 12). In the analysis percentage of myxomatous tissue by Movat staining, there was a significant difference between the DM (G1) groups, with a media of 54.6 % ± 23,7 and control group (G2) with a media of 35.5 % ± 22.5 with p = 0.013. There was an increased number of CD20 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.8 (6.7 - 27.9) x 4.6 (3.6 - 9.8) with p = 0.007 for the area 1. There was a higher number of CD45 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.3 (3.4 - 92.5) x 2.8 (1.4 - 10.1) with p = 0.008 for the area 1. There was a higher number of CD68 cells/mm2 in control group (G2) without a statistically significant difference, with a median of 38.7 (26.6 - 81.8) x 70 (42.7 - 120.4) with p = 0,098 for the area 1. In quantifying Mycoplasma pneumoniae we observed a higher area (um2) antigen marked by, there was a higher amount of antigen detected in myxomatous degeneration group. In area 1, a median of 180,993 (24,856 - 387,477) x 7,970 (2,736 - 15,992) with p < 0.001 and in area 2, a median of 105,968 (2,503 - 416,585) x 7,190 (3,314 - 17,833) with p = 0.02. The analysis of the presence of Chlamydophila pneumoniae antigens showed that in both area, there was a larger area (?m2) antigens detected in the group of valves with MD when compared with the control group, but without significant differences with median for the G1 of 9,905 (4,716 - 16,912) x 5,864 (2,382 - 8,692), with p = 0.2 and the G2, median 3,199 (1,791 - 10,746) x 2,536 (683 - 6,125) with p = 0.3. Regarding the presence of Borrelia burgdorferi antigens, there was a greater area (?m2) antigens detected in group 2 than in group 1, in both areas. In one area, median 7,596 (3,203 - 13,519) x 10,584 (7,223 - 15,974), with p = 0.14 and in area 2, a median of 5,991 (3,009 - 8,475) x 8,403 (1,626 - 27,887) with p = 0.47. Regarding the presence of metalloproteinase MMP9, we observed a higher area (um2) antigen marked by MMP9 in the group with MD both in area 1and area 2, with statistically significant difference. In area 1, median of 503,894 (202,428 - 938,072) x 269,244 (111,953 - 354,022), p = 0.03. In area 2, median 389,844 (214,459 - 679,711) x 144,397 (29,894 - 247,453) with p < 0.001. In the DM group there was a positive correlation between Borrelia burgdorferi and the percentage of MD with R = 0.52 and p = 0.018. Regarding inflammatory cells, there was a positive correlation between CD45 and Mycoplasma pneumoniae with R = 0.51 and p = 0.02. The presence of MMP9 was positively correlated with the presence of Mycoplasma pneumoniae with R = 0.45 and p = 0.04. These correlations were absent in the control group. Conclusions: There was an association of infectious agents Mycoplasma pneumoniae and Borrelia burgdorferi in etiopathogeny of myxoid degeneration of the mitral valve. In the analysis of the relationship of bacterial products with the inflammatory markers and the metalloproteinase, there was a positive relationship between the inflammatory marker CD45 and metalloproteinase (MMP9) only with Mycoplasma pneumoniae. The inflammatory marker CD68 was found in greater numbers in the control group

Since living conditions have improved and antibiotics have entered routine use, valvular heart disease (VHD) in the developed world is mostly degenerative in origin, rather than rheumatic. Our population is increasing with age, and therefore the burden of VHD is likely to increase. Despite this, the epidemiology & prognostication in VHD remain poorly understood. A better understanding of the prevalence of VHD in our population, and improved methods of predicting outcomes, are essential if we are to be better equipped to meet the challenges of this new “epidemic”. This thesis aims to improve our knowledge of the prevalence of VHD in the elderly, and the potential benefits of cardiac magnetic resonance (CMR) assessment of patients with clinically significant mitral regurgitation. The prevalence of undiagnosed valvular heart disease in those aged 65 and over is examined in Chapters 2 and 3. Chapter 2 outlines a population-based screening study for VHD in primary care in Oxfordshire, which the author played a central role in establishing. The results show that VHD is extremely common in this cohort, and is strongly associated with increasing age. In chapter 4, the level of anxiety provoked by screening for VHD is looked at; this demonstrates that only a small number of patients have significant anxiety levels, but it is more likely in those with a new diagnosis of VHD, and in women. From Chapter 5 onwards, the thesis focuses on the use of CMR in patients with significant mitral regurgitation (MR). In Chapter 5, the clinical value of quantitative assessment of MR using CMR is examined, showing that it was able to predict progression to symptoms or surgery in these patients. In conclusion, this thesis offers insights into the prevalence of VHD in the elderly population, and looks at the anxiety associated with looking for VHD in this group. The potential clinical benefits of CMR in patients with MR are examined, and quantification of MR with this modality would appear to be of prognostic utility.

Introdução e Objetivo: A doença mixomatosa da valva mitral leva ao comprometimento de sua matriz devido à alteração em sua composição tecidual provocada pelo desequilíbrio na quantidade de ácidos mucopolissacarídeos ou glicosaminoglicanos. Sua etiologia ainda não está totalmente esclarecida, podendo ocorrer em formas familiares com transmissão autossômica dominante de penetrância variável, que pode ser dependente do tempo ou de prováveis fatores ambientais, situações em que a interação de agentes infecciosos necessita de maiores esclarecimentos. O objetivo deste estudo é a análise dos produtos dos patógenos da Chlamydophila pneumoniae, Mycoplasma pneumoniae e Borrelia burgdorferi em segmentos de cúspide retirados da valva mitral com degeneração mixomatosa, comparada ao grupo controle e a relação dos produtos bacterianos com aumento de marcadores inflamatórios (CD20, CD48, CD68) e de metaloproteinase (MMP9) na etiopatogenia da degeneração mixomatosa da valva mitral. Método: Estudo observacional, analítico, tipo caso-controle, que analisou 2 grupos contendo 20 pacientes cada e divididos em grupo 1, composto por fragmentos de tecido valvar mitral com diagnóstico de degeneração mixomatosa extraídos em procedimentos de troca ou plásticas valvares mitrais; e grupo 2, formado por segmentos de valvas mitrais sem valvopatia retirados no serviço de verificação de óbito. Foram realizadas colorações de hematoxilina e eosina e Movat para diagnóstico histológico da degeneração mixomatosa e técnica de imunohistoquímica para detecção de antígenos da Borrelia burgdorferi, Mycoplasma pneumoniae, mediadores inflamatórios (CD20, CD45, CD68) e marcadores de metaloproteinase (MMP9). A presença de antígenos da Chlamydophila pneumonia e foi pesquisada pela técnica de hibridização in situ. A análise quantitativa dos aspectos microscópicos foi realizada com o analisador de imagens Aperio. A pesquisa de elementos bacterianos foi feita através de microscopia eletrônica de transmissão. Resultados: No grupo 1, 14 (70%) pacientes são do gênero masculino e 6 (30%) do gênero feminino. A idade média é de 67,4 anos (51 a 79 anos, dp = 9,2). No grupo 2, 11 (55%) pacientes são do gênero masculino e 9 (45%) do gênero feminino. A idade média é de 67,6 anos (42 a 84 anos, dp= 12,0). Na análise da porcentagem de degeneração mixomatosa pela coloração Movat, houve diferença com significância estatística entre os grupos DM (G1), com média de 54,6 % ± 23,7 e grupo controle (G2) com média de 35,5 % ± 22,5 com valor de p = 0,013. Houve um maior número de células CD20 positivas/mm2 no grupo com DM com mediana igual a 17,8 (6,7 - 27,9) x 4,6 (3,6 - 9,8) com p = 0,007 para a área 1. Houve maior número de células CD45 positivas/mm2 no grupo com DM com mediana igual a 17,3 (3,4 - 92,5) x 2,8 (1,4 - 10,1) com p = 0,008 para a área 1. Houve maior número de células CD68 positivas/mm2 no grupo controle (G2), porém sem significância estatística com mediana igual a 38,7 (26,6 - 81,8) x 70 (42,7 - 120,4) com p = 0,098 para a área 1. Em relação à presença de antígenos de Mycoplasma pneumoniae, houve uma maior área (?m2) de antígenos detectados no grupo 1, quando comparadas com o grupo 2 com diferença estatisticamente significante para as duas áreas. Na área 1, mediana de 180.993 (24.856 - 387.477) x 7.970 (2.736 - 15.992) com p < 0,001 e na área 2, mediana igual a 105.968 (2.503 - 416.585) x 7.190 (3.314 - 17.833) com p = 0,02 A análise da presença de antígenos de Chlamydophila pneumoniae demonstrou que em ambas as áreas, houve uma maior área (?m2) de antígenos detectados no grupo de valvas com degeneração mixomatosa, quando comparadas com o grupo controle, porém sem diferença estatística com mediana para o G1 de 9.905 (4.716 - 16.912) x 5.864 (2.382 - 8.692) com p = 0,2 e para o G2, mediana de 3.199 (1.791 - 10.746) x 2.536 (683 - 6.125) com p = 0,3. Em relação à presença de antígenos de Borrelia burgdorferi, houve uma maior área (um2) de antígenos detectados no grupo 2 em relação ao grupo 1, em ambas as áreas. Na área 1, mediana de 7.596 (3.203 - 13.519) x 10.584 (7.223 - 15.974) com p = 0,14 e na área 2, mediana igual a 5.991 (3.009 - 8.475) x 8.403 (1.626 - 27.887) com p = 0,47. Em relação à presença da metaloproteinase MMP9, observamos maior área (um2) de antígeno marcado de MMP9 no grupo com degeneração mixomatosa tanto na área 1 quanto na área 2, com diferença estatística significante. Na área 1, mediana de 503.894 (202.428 - 938.072) x 269.244 (111.953 - 354.022) com p = 0,03. Na área 2, houve diferença estatística representada pela mediana de 389.844 (214.459 - 679.711) x 144.397 (29.894 - 247.453) com p < 0,001. No grupo DM houve correlação positiva entre Borrelia burgdorferi e porcentagem de DM com R = 0,52 e p = 0,018. Em relação às células inflamatórias, houve correlação positiva entre CD45 e Mycoplasma pneumoniae com R = 0,51 e p = 0,02. A presença de MMP9 se correlacionou positivamente com a presença de Mycoplasma pneumoniae com R = 0,45 e p = 0,04. Estas correlações estiveram ausentes no grupo controle. Conclusões: Houve associação de agentes infecciosos Mycoplasma pneumoniae e Borrelia burgdorferi na etiopatiopatogenia da degeneração mixomatosa da valva mitral. Na análise da relação dos produtos bacterianos com os marcadores inflamatórios e com a metaloproteinase, houve relação positiva entre o marcador inflamatório CD45 e a metaloproteinase (MMP9) apenas com a Mycoplasma pneumoniae, nas valvas com degeneração mixomatosa. O marcador inflamatório CD68 foi encontrado em maior número no grupo controle / Background: The myxomatous mitral valve disease leads to impairment due to changes in their tissue composition caused by the imbalance in the amount of acid mucopolysaccharides or glycosaminoglycans. Its etiology is not yet fully understood and may occur in familial forms of autosomal dominant trait with variable penetrance that can be time-dependent or probable environmental factors, where the interaction of infectious agents requires further elucidation. The purpose of this study is the analysis of the pathogens products of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi in removed cusp segments of the mitral valve with myxoid degeneration, compared to the control group and the ratio of bacterial products with increased inflammatory markers (CD20, CD48, CD68) and metalloproteinase (MMP9) in the pathogenesis of myxomatous degeneration of the mitral valve. Method: Observational, analytical, case-control study which analyzed 2 groups of 20 patients each and divided in group 1, consisting of fragments of mitral valve tissue with diagnosis of myxomatous degeneration extracted in replacement procedures or mitral valve repair; group 2, formed by segments of mitral valves without valvolpaty clinial disease removed in the coroner service. Hematoxylin and eosin and Movat stains were done for histological diagnosis of myxoid degeneration and immunohistochemical technique for the detection of Borrelia burgdorferi, Mycoplasma pneumonia antigens, inflammatory mediators (CD20, CD45, CD68) and markers of metalloproteinase (MMP9). The presence of Chlamydophila pneumonia antigens was verified through an in situ hybridization technique. The quantitative analysis of the microscopic aspects was performed with the Aperio image analyzer. The research of bacterial elements was performed by a transmission electron microscopy. Results: In group 1, 14 (70%) patients were male and 6 (30%) were female. The mean age was (51 to 79 years, sd = 9.2). In group 2, 11 (55%) patients were male gender and 9 (45%) were female. The mean age was 67,6 years (42 to 84 years, sd= 12). In the analysis percentage of myxomatous tissue by Movat staining, there was a significant difference between the DM (G1) groups, with a media of 54.6 % ± 23,7 and control group (G2) with a media of 35.5 % ± 22.5 with p = 0.013. There was an increased number of CD20 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.8 (6.7 - 27.9) x 4.6 (3.6 - 9.8) with p = 0.007 for the area 1. There was a higher number of CD45 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.3 (3.4 - 92.5) x 2.8 (1.4 - 10.1) with p = 0.008 for the area 1. There was a higher number of CD68 cells/mm2 in control group (G2) without a statistically significant difference, with a median of 38.7 (26.6 - 81.8) x 70 (42.7 - 120.4) with p = 0,098 for the area 1. In quantifying Mycoplasma pneumoniae we observed a higher area (um2) antigen marked by, there was a higher amount of antigen detected in myxomatous degeneration group. In area 1, a median of 180,993 (24,856 - 387,477) x 7,970 (2,736 - 15,992) with p < 0.001 and in area 2, a median of 105,968 (2,503 - 416,585) x 7,190 (3,314 - 17,833) with p = 0.02. The analysis of the presence of Chlamydophila pneumoniae antigens showed that in both area, there was a larger area (?m2) antigens detected in the group of valves with MD when compared with the control group, but without significant differences with median for the G1 of 9,905 (4,716 - 16,912) x 5,864 (2,382 - 8,692), with p = 0.2 and the G2, median 3,199 (1,791 - 10,746) x 2,536 (683 - 6,125) with p = 0.3. Regarding the presence of Borrelia burgdorferi antigens, there was a greater area (?m2) antigens detected in group 2 than in group 1, in both areas. In one area, median 7,596 (3,203 - 13,519) x 10,584 (7,223 - 15,974), with p = 0.14 and in area 2, a median of 5,991 (3,009 - 8,475) x 8,403 (1,626 - 27,887) with p = 0.47. Regarding the presence of metalloproteinase MMP9, we observed a higher area (um2) antigen marked by MMP9 in the group with MD both in area 1and area 2, with statistically significant difference. In area 1, median of 503,894 (202,428 - 938,072) x 269,244 (111,953 - 354,022), p = 0.03. In area 2, median 389,844 (214,459 - 679,711) x 144,397 (29,894 - 247,453) with p < 0.001. In the DM group there was a positive correlation between Borrelia burgdorferi and the percentage of MD with R = 0.52 and p = 0.018. Regarding inflammatory cells, there was a positive correlation between CD45 and Mycoplasma pneumoniae with R = 0.51 and p = 0.02. The presence of MMP9 was positively correlated with the presence of Mycoplasma pneumoniae with R = 0.45 and p = 0.04. These correlations were absent in the control group. Conclusions: There was an association of infectious agents Mycoplasma pneumoniae and Borrelia burgdorferi in etiopathogeny of myxoid degeneration of the mitral valve. In the analysis of the relationship of bacterial products with the inflammatory markers and the metalloproteinase, there was a positive relationship between the inflammatory marker CD45 and metalloproteinase (MMP9) only with Mycoplasma pneumoniae. The inflammatory marker CD68 was found in greater numbers in the control group

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-08T14:29:39Z No. of bitstreams: 2 MARILIA AVILA VALANDRO ok.pdf: 1044698 bytes, checksum: 07606147cdffad848dc4db44d0162dd3 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-08T14:30:12Z (GMT) No. of bitstreams: 2 MARILIA AVILA VALANDRO ok.pdf: 1044698 bytes, checksum: 07606147cdffad848dc4db44d0162dd3 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2016-09-08T14:30:12Z (GMT). No. of bitstreams: 2 MARILIA AVILA VALANDRO ok.pdf: 1044698 bytes, checksum: 07606147cdffad848dc4db44d0162dd3 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2016-03-29 / A endocardiose valvar (EV) é a cardiopatia mais prevalente na espécie canina, capaz de alterar o balanço autonômico pela ativação crônica do sistema nervoso simpático, relacionado ao risco de morte súbita e pior prognóstico. Diversos programas de treinamento com caminhada foram eficazes no restabelecimento do equilíbrio autonômico em seres humanos cardiopata, verificados a luz da variabilidade da frequência cardíaca (VFC). Dessa forma, objetivou-se avaliar o efeito de oito semanas de caminhada, realizadas três vezes por semana, durante 30 a 50 minutos, de moderada intensidade (60 a 80% da frequência cardíaca máxima), sobre a função autonômica cardíaca de cães com EV, utilizando a VFC no domínio do tempo e da frequência como ferramenta. Para tanto, 20 cães com EV foram divididos em dois grupos: grupo controle - não treinado (GC, n=9) e grupo treinamento (GT, n=11), e avaliados nos momentos basal (T0), quatro semanas (T1) e oito semanas (T2). No domínio do tempo, a variável média rMSSD (raiz quadrada da média ao quadrado das diferenças sucessivas entre os intervalos NN) foi maior no GT em quatro (155,5+42,07) e oito semanas (199,8+83,54) em relação ao GC (91,17+35,79 e 88,17+57,51) (p<0,05). No domínio da frequência, a variável High Frequency (HF) foi a mais representativa, e apresentou aumento no GT (30950+25810) após quatro semanas quando comparado ao GC (19090+23210) (p<0,05) e dentro do grupo GT após oito semanas de treinamento (40300+33870) em relação à avaliação basal (29340+20950) (p<0,05). As demais variáveis não sofreram influências do programa de treinamento proposto. Esses resultados demonstram que o treinamento físico com a utilização de caminhadas foi capaz de alterar a VFC, indicando uma maior participação parassimpática em cães com EV. / Valvular endocardiosis is the most prevalent cardiopathy in canine specie. This disease is able to change autonomic balance, which is related to sudden death and worse prognostic, through chronic activation of sympathetic nervous system. Looking at heart rate variability, various walk training plans were efficient for the autonomic balance reestablishment in cardiophats people. In this way, this study focused on evaluate the effect of 8 weeks walking plan on cardiac autonomic function of dogs with valvular endocardiosis. These walking plans were consisted of moderated intensity walking (reaching from 60 to 80% of maximum heart rate) during 30 to 50 minutes, three times a week. Heart rate variability was analyzed by utilizing time and frequency domain as a tool. Thus, 20 dogs with valvular endocardiosis were divided into two groups: Control group, with no training (CG, n=9), and Training group (TG, n=11). They were evaluated at basal moment (T0), 4 weeks (T1), and 8 weeks (T2). At time domain, only the medium variable rMSSD (the root mean square of successive differences between the square NN intervals) was higher in the TG in four (155.5+42.07) and eight weeks (199.8+83.54) than CG (91.17+35.79 and 88.17+57.51) (p<0.05). At frequency domain, the high frequency variable was the most representative and after four weeks, it showed higher on TG (30950+25810) than CG (19090+23210) (p<0.05). After eight weeks, within TG there was higher frequency (40300+33870) when compared to basal evaluation (29340+20950) (p<0.05). The proposed training program did not affect the other variables. These results suggest that the physical training with utilization of walking plans were able to change the heart rate variability what indicated a higher parasimpathetic participation of dogs with valvular endocardiosis.