Objective: To determine whether echocardiography affects the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients suspected of having mitral valve prolapse (MVP). Design: Retrospective review of echocardiograms and clinical records. Setting: Military tertiary care hospital. Patients: 127 patients with clinically suspected MVP (105) or incidentally discovered MVP (22). Main results: Beta blockers were used more often in patients with suspected MVP and positive echocardiograms (45%) than in patients with normal echocardiograms (13%, p<0.001). Bacterial endocarditis prophylaxis was recommended more often in patients with suspected MVP and positive echocardiograms (65%) than in patients with normal echocardiograms (11%, p<0.001). Presence or absence of a murmur did not influence the decision to recommend bacterial endocarditis prophylaxis. Patients in whom MVP was incidentally discovered were unlikely to receive either beta blockers or the recommendation for bacterial endocarditis prophylaxis. Conclusions: The results of echocardiography affect the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients with suspected MVP.

Cardiovascular involvement is commonly reported in various muco- polysaccharidoses. We report a first case of Sanfilippo syndrome type A in a 12-year-old white female who has developed combined progressive mitral valvar regurgitation due to prolapse and aortic regurgitation.

No description available.

Objectives: To further characterize the echocardiographic anatomy of the canine mitral valve in healthy dogs and those affected by myxomatous mitral valve disease (MMVD), and to compare the level of agreement between two methods of assessment of left atrial size in identification of left atrial enlargement in dogs with MMVD. Animals: Sixty dogs with MMVD and 22 normal dogs were prospectively studied with 2-dimensional echocardiography. Methods: The length (AMVL), width (AMVW) and area (AMVA) of the anterior mitral valve leaflet and the diameter of the mitral valve annulus in systole (MVAs) and diastole (MVAd) were measured. Left atrial size was evaluated with the left atrial to aortic root ratio (LA:Ao) and by measuring left atrial volume indexed to body weight (LA Vol/BW). All patients were staged using published ACVIM guidelines and separated into groups B1 and B2/C. Results: Measurements of AMVL, AMVW, AMVA, MVAs and MVAd were all significantly greater in the B2/C group than in the control group. AMVW was significantly greater in group B1 than control. Twelve dogs had left atrial enlargement identified with LA Vol/BW that were considered normal using LA:Ao. Diagnostic disagreement between these two measurements was significant (P = 0.00012). The majority of dogs with diagnostic disagreement had concurrent echocardiographic evidence of more advanced mitral regurgitation. Conclusions: Relative to normal dogs, AMVL, AMVW, AMVA, MVAs and MVAd are greater in patients with advanced MMVD. LA Vol/BW may be superior to LA:Ao for identification of mild left atrial enlargement. / Master of Science

Myxomatous mitral valve disease (MMVD) is one of the most common degenerative cardiac diseases affecting humans and dogs; however, its pathogenesis is not completely understood. This study focussed on developing tissue-engineered fibrin based canine mitral valve constructs, which can be used as an in vitro platform to study the pathogenesis of MMVD. Prior to three dimensional (3D) construct fabrication, primary canine mitral valve endothelial cells (VECs) and valve interstitial cells (VICs) were isolated, cultured and characterized utilising a variety of techniques. Moreover, preliminary experiments were carried out to optimise the purity of VEC cultures. It is uncertain if canine MMVD is initiated by long term shear stress damage to the valve endothelium or from abnormalities of VICs. To investigate both hypotheses, three types of models were produced using fibrin/based 3D culture techniques: healthy VEC-VIC co-culture (Type 1); healthy VEC-diseased VIC co-culture (Type 2); healthy VEC-VIC co-culture with endothelial damage during culture (Type 3). Histological examination demonstrated partial native tissue-like morphology of the 3D constructs. Results suggest that current static cultured constructs express MMVD markers irrespective of using healthy or diseased VICs. Simple mechanical stimulation was found to regulate VIC activity in the 3D models. Endothelial damage resulting in VIC phenotypic activation (a change typically observed in MMVD), and decreased mechanical tension appeared to be a negative regulator of this effect. Moreover, there appears to be heterogeneity in the activated VIC population. Additionally, distinct advanced glycation end product (AGE) carboxymethyllysine (CML) expression was found in canine MMVD valves, which suggesting this biochemical compound (known to affect long living protein) might be a putative regulator of MMVD pathogenesis. The role of CML in MMVD can be further investigated utilizing current 3D static mitral valve construct model in future studies. Lastly a prototype dynamic tubular construct and a customised bioreactor system were developed. Preliminary data suggest the feasibility of tubular construct fabrication and endothelialisation, which provides foundation for future dynamic conditioning experiments and will allow examination of the role of endothelial shear stress in triggering MMVD. In summary, this project successfully developed fibrin based canine mitral valve constructs. It is believed they are promising models for MMVD research, allowing new insights in understanding MMVD pathogenesis.

Die vorliegende Arbeit beschreibt die Rolle der intraoperativen transösophagealen Echokardiografie während herzchirurgischer Eingriffe mit Schwerpunkt Mitralklappenrekonstruktion. Ziel ist die Beschreibung der Aufgaben und Möglichkeiten dieses Verfahrens im klinischen Alltag und das Aufzeigen möglicher neuer Einsatzgebiete, wie die bildgestützte Größenbestimmung der Annuloplastieringe. Die intraoperative Echokardiografie hat sich seit den Anfängen in den achtziger Jahren des letzten Jahrhunderts zu einem Standardverfahren während herzchirurgischer Eingriffe entwickelt. Sie dient zum einen zur kardialen Diagnostik und zum anderen als Monitorverfahren. Trotz in der Regel gut vordiagnostizierter Patienten führt die intraoperativ durchgeführte transösophageale Echokardiografie während herzchirurgischer Eingriffe nicht selten zur Diagnose vorher nicht bekannter Pathologien und somit zu einer Änderung im chirurgischen Vorgehen. Speziell während der Mitralklappenrekonstruktion ermöglicht diese Methode die Diagnostik und Lokalisation der pathologischen Segmente, die Bestätigung des Schweregrades und dem Erkennen möglicher Risikofaktoren. Hierfür ist jedoch eine umfassende, standardisierte Untersuchung notwendig. Der Einsatz moderner Operationstechniken, wie z.B. der kathetergestützten Implantation der Aortenklappe ohne Einsatz der Herz-Lungen-Maschine, ohne Eröffnung des Sternums, macht eine direkte visuelle Einschätzung der Herzfunktion unmöglich. Sowohl zur Evaluierung der Herzfunktion als auch zur Größenbestimmung der zu implantierenden Klappenprothesen ist ein bildgebendes Verfahren unabdingbar. Die dreidimensionale transösophageale Echokardiografie ermöglicht nun in Echtzeit die komplette Darstellung z.B. der Mitralklappe. Dies erleichtert nicht nur die Verständigung zwischen Echokardiographeur und Chirurgen bei der Darstellung der Befunde, sondern ermöglicht nun erstmals auch die bildgestützte Planung des operativen Vorgehens, wie, z.B. die Visualisierung und Größenbestimmung der zu implantierenden Annuloplastieringe, die als Computermodelle auf die dreidimensionale Darstellung der Mitralklappe projiziert werden können. In der postoperativen TEE-Untersuchung ist die Evaluierung des rekonstruierten Mitralklappenapparates, die Quantifizierung einer eventuell bestehenden residualen Mitralinsuffizienz, sowie deren genaue Lokalisation primäres Ziel. Weiterhin sollten iatrogen aufgetretene Komplikationen in einer umfassenden postoperativen TEE-Untersuchung diagnostiziert werden wie z.B. der Verschluss des Ramus circumflexus, Aortendissektion, etc. Zusammenfassend wird in dieser Habilitationsarbeit die Rolle der intraoperativen Echokardiografie bei herzchirurgischen Eingriffen dargestellt. Ein besonderer Schwerpunkt in dieser Arbeit ist die transösophageale Echokardiographie bei Mitralklappenoperationen im Hinblick auf die Darstellung der bestehenden Pathologie, der Quantifizierung der Mitralinsuffizienz und dem Erkennen bestehender Risikofaktoren präoperativ bzw das Erkennen der Komplikation postoperativ.

The material properties of the mitral valve chordae tendineae are important for the understanding of leaflet coaptation configuration and chordal pathology. This research combines basic histology with standard mechanical tests to determine the functioning role of the chordae tendineae during the cardiac cycle. Dual camera stereo photogrammetry was used to measure strains of the chordae in vitro under normal physiologic loading conditions. A uniaxial test simulating the same loading conditions was conducted. Histology and biochemical assays were performed on the chordae to determine chordal microstructure. Six porcine mitral valves were used for the in vitro flow loop study. The maximum strain experienced was 4.29% l 3.43% and was experienced at 249 msec after the start of valve closure. The loading rate was slightly higher than the unloading rate. The anterior lateral strut chordae had a higher maximum strain and loading rate than the posterior medial strut chordae. The posterior medial strut chordae had a higher unloading rate than the anterior lateral strut chordae. Histological examination revealed blood vessels in the chordae. The anterior strut chordae contain significantly more vessels than the other chordae. Different structural levels were observed for all chordae. The inner layer was characterized by a higher concentration of collagen; whereas, the middle layer was collagen with interwoven elastin fibers. The collagen microstructure was characterized by directional crimping. The anterior and posterior marginal chordae contained significantly more DNA than the other chordae (p<0.01). The anterior strut chord was found to contain significantly less DNA than all the other chordae (p<0.01). The collagen assay results showed that the posterior marginal chord contained significantly more collagen than the other chordae (p<0.01). The Fastin Elastin assay results showed no significant difference in the amount of elastin between the chordae. This study demonstrates the first in vitro examination of the strain experienced by the chordae tendineae of the mitral valve. This technique allows the investigation of the behavior of biological tissues under physiologic loading conditions. Contrary to earlier belief, vessels were found in the chordae. The microstructure and biochemical composition of the chordae tendineae is related to their function during coaptation.

Currently, mitral valve repair techniques have shown substandard mid-term and long term results. In order to improve the efficacy of these repair techniques, detailed knowledge of normal mitral valve function and the alterations to the valvular and subvalvular apparatus which occur under pathological conditions is required. Furthermore, current techniques may be optimized through a better understanding of the function and mechanics of the mitral valve after a particular repair. The experiments which comprise this study were designed using an in vitro approach since this technique has the clear advantage of isolating and independently controlling specific parameters that are of importance to valvular mechanics and function. The experiments were conducted in the Georgia Tech Left Heart Simulator using native porcine and human mitral valves. The first set of experiments measured the chordal force distribution and anterior leaflet strain of the mitral valve in its normal geometrical configuration. Subsequent experiments measure mitral regurgitation volume and chordal force distribution in conditions associated with ventricular dilation. The last set of experiments simulated two commonly used mitral repair techniques. For the Alfieri stitch experiments, the effects of mitral flow rate, transmitral pressure, and mitral annular area on valve stenosis, mitral regurgitation and Alfieri stitch force were evaluated. For annuloplasty, the effect of annular saddle curvature on anterior leaflet strain was quantified. In Conclusion, the normal geometry of the native mitral valve optimized its function and mechanics. Under pathological conditions associated with ventricular dilation, significant alterations to mitral valve function and mechanics were present. Although the studied repair techniques may have significantly restored valve function, severe alterations to the mechanics of the valve still persisted.

Mitral valve disease is widely prevalent among pediatric and adult population across the world, and it encompasses a spectrum of lesions which include congenital valve defects, degenerative valve lesions, and valve dysfunction due to secondary pathologies. Though replacement of the diseased mitral valves with artificial heart valves has been the standard of care until early 1990's, current trends have veered towards complete surgical repair. These trends are encouraging, but current repair techniques are plagued with lack of durability and high rates of failure within 10 years after repair. With increasing number of patients receiving mitral valve repair, there is now an immediate need to understand the mechanisms of repair failure, and assess the role of several clinical risk factors on valve repair. In this thesis, an in vitro pulsatile left heart simulator was developed to mimic the congenital and adult mitral valve pathological morphologies in normal porcine valves, and simulate the pathological valve hemodynamics and mechanics. Different surgical repair techniques were used to correct the valve lesions, and the post repair valve hemodynamics, mechanics and geometry were assessed using quantitative measurement techniques. The extent to which each repair restores physiological valve function and mechanics was assessed, and the impact of different pathological risk factors on repair failure mechanisms was investigated. It is expected that the knowledge from this thesis would play an important role in the evolution of mitral valve surgical repair, and guide the development of more effective and long-lasting heart valve repair technologies.

Este estudo avalia mortalidade, reoperação e eventos hemorrágicos em pacientes submetidos à cirurgia para troca valvar mitral utilizando substituto biológico ou mecânico. O delineamento do estudo foi do tipo coorte histórica. Entre todos os registros, foram selecionados 352 prontuários de pacientes submetidos à cirurgia para troca valvar mitral entre 1990 e 2008, que tiveram seguimento mínimo de 5 e máximo de 23 anos. Para avaliar o tempo de sobrevida, a probabilidade de reoperação e de eventos hemorrágicos, foi utilizada a curva de Kaplan-Meier. Foi aplicado, para comparar as curvas entre os grupos, o teste qui-quadrado de Log-rank. A análise multivariada de Regressão de Cox foi utilizada para identificar preditores independentes de mortalidade, reoperação e eventos hemorrágicos. A sobrevivência em 5, 10, 15 e 20 anos após cirurgia utilizando substituto mecânico foi de 87,7%, 74,2%, 69,3% e 69,3% e, para substituto biológico, foi de 87,6%, 71,0%, 64,2%, e 56,6%, respectivamente. Não houve diferença significativa entre a mortalidade entre os dois grupos (p=0,38). Na análise multivariada, os fatores associados com o óbito foram: idade, eventos hemorrágicos e insuficiência renal. A probabilidade de permanecer livre de reoperação em 5, 10, 15 e 20 anos após cirurgia utilizando substituto mecânico foi de 94,4%, 92,7%, 92,7% e 92,7% e, para bioprótese, foi de 95,9%, 86,4%, 81,2% e 76,5%, respectivamente (p=0.073), com uma incidência significativamente maior de reoperação para bioprótese (p=0,008). Os fatores associados com reoperação foram: sexo masculino, diâmetro da prótese e endocardite. A probabilidade de permanecer livre de eventos hemorrágicos em 5, 10, 15 e 20 anos após cirurgia utilizando substituto mecânico foi de 95,0%, 91,0%, 89,6% e 89,6% e, para bioprótese, foi de 96,9%, 94,0%, 94,0% e 94,0%, respectivamente (p=0,267). Os fatores associados com eventos hemorrágicos foram: IMC (índice de massa corporal) superior à 30 kg/m2, doença pulmonar obstrutiva crônica, tempo de ventilação mecânica na Unidade de Tratamento Intensivo superior a 30 dias e presença insuficiência mitral. Os autores concluíram que: 1) a mortalidade foi estatisticamente semelhante entre os dois grupos no seguimento; 2) houve tendência maior à reoperação no grupo com bioprótese; 3) após 10 anos de seguimento, a probabilidade de permanecer livre de reoperação não mudou para pacientes com substitutos valvares mecânicos; 4) a probabilidade de permanecer livre de eventos hemorrágicos não mudou após 10 anos de seguimento para portadores de biopróteses; 5) as características basais dos pacientes foram os maiores determinantes de mortalidade tardia após a cirurgia; 6) o tipo de prótese não foi fator preditor independente associado a nenhum dos desfechos avaliados na análise multivariada. / This study assessed mortality, reoperation and bleeding events in patients who underwent mitral valve replacement surgery with a biological or mechanical substitute. This was a historical cohort study. In total, 352 inpatients clinical health records who underwent mitral valve replacement surgery between 1990 and 2008 with 5 to 23 years of follow-up were selected. A Kaplan-Meier curve was used to evaluate the survival time, the probability of reoperation and bleeding events. A log-rank chi-square test was applied to compare the curves between groups. Multivariate Cox regression analysis was used to identify independent predictors of mortality, reoperation and bleeding events. The 5, 10, 15 and 20 year survival rates after surgery using a mechanical substitute were 87.7%, 74.2%, 69.3% and 69.3%, respectively, while the survival rates after surgery with a biological substitute were 87.6%, 71.0%, 64.2% and 56.6%, respectively. There was no significant difference in mortality between the two groups (p = 0.38). In the multivariate analysis, the factors associated with death were age, bleeding events and renal failure. The probabilities of being free of reoperation at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 94.4%, 92.7%, 92.7% and 92.7%, respectively, while after surgery with a bioprosthesis, they were 95.9%, 86.4%, 81.2% and 76.5%, respectively (p = 0.073); therefore, there was a significantly higher incidence of reoperation for patients receiving a bioprosthesis (p = 0.008). The factors associated with reoperation were male gender, diameter of the prosthesis and endocarditis. The probabilities of remaining free of bleeding events at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 95.0%, 91.0%, 89.6% and 89.6, respectively, while after surgery with a bioprosthesis, they were 96.9%, 94.0%, 94.0% and 94.0%, respectively (p = 0.267). The factors associated with bleeding events were BMI (body mass index) greater than 30 kg/m2, chronic obstructive pulmonary disease, mechanical ventilation at an Intensive Care Unit for longer than 30 days and mitral regurgitation. The authors concluded that: 1) mortality during follow-up was statistically similar in both groups; 2) there was a greater tendency to reoperation in the bioprosthesis group; 3) the probability of survival free from reoperation did not change for patients with mechanical valves after 10 years’ follow-up; 4) the probability of survival free from bleeding events did not change after 10 years’ follow-up for bioprostheses patients; 5) patients’ baseline characteristics were the greatest determinants of late mortality after mitral valve replacement surgery; 6) the type of prosthesis fitted was not an independent predictive factor of any of the outcomes analyzed in the multivariate analysis.