Abstract The repair of degenerative mitral valve regurgitation has been shown to be an effective procedure with durable results. The techniques for mitral valve repair are not completely risk-free for late failure, and the identification of factors associated with this increased risk is of clinical relevance as it permits an appropriate selection of patients for whom mitral valve surgery should be offered and by which technique. The European system for cardiac operative risk evaluation score (EuroSCORE) has been used and demonstrated worldwide to be a valid tool for the prediction of immediate postoperative outcome after coronary artery bypass surgery. There are only a few studies which examine its value in heart valve surgery. Mitral valve repair has been shown to be associated with significant improvement in terms of functional capacity, but the late quality of life in these patients has not been adequately assessed, and there is no data on the quality of life of long-term survivors. The study population consisted of two groups of patients operated on at our institution. The first group included 164 patients who underwent isolated or combined mitral valve repair for mitral valve regurgitation during the period 1993 to 2000, while the second group consisted of 207 patients who underwent mitral valve repair (164 patients) or replacement (43 patients) for isolated mitral valve regurgitation during the same time-period. The first study aimed to identify preoperative variables which may have impact on the 30-day postoperative outcome. In the second study, the long-term outcome after mitral valve repair was evaluated in order to identify the risk factors associated with late failures. The third study analyzed quality of life after valve repair and compared it to that of an age- and gender-adjusted Finnish general population. In the fourth study, the validity of EuroSCORE was tested in predicting the immediate and late outcome of patients who had undergone mitral valve repair or replacement for isolated valve regurgitation. Patient age, a history of prior cardiac surgery and NYHA functional class were independent predictors of poor outcome. A residual regurgitation grade of more than one immediately after primary repair and chronic pulmonary disease were independent predictors of mitral valve reoperation. After valve repair, quality of life was similar to the age- and sex-adjusted general Finnish population. Both additive and logistic EuroSCOREs were predictors of the immediate and late outcomes of patients after surgery for mitral valve regurgitation.

Ce travail de doctorat se décompose en quatre parties distinctes. La première partie concerne la caractérisation hémodynamique sur simulateur cardiovasculaire de prothèses valvulaires mitrales de différents constructeurs en vue de leur évaluation clinique et du diagnostique de leur dysfonction. La seconde partie se focalise sur les prothèses valvulaires mécaniques bi-clapet au travers desquels le phénomène de recouvrement de pression dû au passage de l'écoulement à travers les trois orifices formés par les clapets peut engendrer une surestimation du gradient transvalvulaire. Ce phénomène peut entrainer une ambiguïté lors de l'évaluation de la prothèse en cas de gradient transvalvulaire important. Cette partie s'attache à quantifier ce phénomène et à évaluer l'influence d'une dysfonction (disproportion patient-prothèse ou obstruction d'un clapet) sur celui-ci. La troisième partie concerne la procédure valve-in-valve dans laquelle une prothèse percutanée est implantée dans une bioprothèse défaillante. Elle fournit une caractérisation in vitro, première au niveau mondial, d'assemblages de la prothèse SAPIEN Edwards dans des bioprothèses issues de différents constructeurs. Enfin et suite à la mise en évidence dans les parties précédentes de profils de vitesse en amont de la prothèse ne pouvant être assimilés à des profils plats, l'étude des patrons de flux auriculaires a été réalisée grâce à des acquisitions in-vitro. / This PhD work is divided into four different parts. the first part concerns the hemodynamic characterization by in-vitro cardiovascular testing of mitral valvular prosthesis from different manufacturers in order to provide reference values for clinical diagnosis. The second part focus on bi leaflet mechanical heart valve in each pressure recovery resulting of flow through the three orifices could lead to an overestimation of transvalvular pressure gradient. This could create ambigious assessment in case of high value of transvalvular pressure gradient. This part aims to quantify this pressure recovery and identify the influence of dysfunction (leaflet obstruction or patient prosthesis mismatch) on this value. Third part consists in valve-in-valve procedure in which a transcatheter valve is impllanted in a failled bioprosthesis. It provides in vitro testing, first globally, of assemblies composed of SAPIEN Edwards prostheses in different manufacturers' bioprosthesis.As highlighted in the previous parts inflows of the mitral prostheses can not be considered as plane and results of left atrium flow patterns. The last part studies the left atrium flow following mitral valve replacement.

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.

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.

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.

Heutzutage stellt der Erhalt des posterioren Halteapparates beim Mitralklappenersatz (MKE) ein Routineverfahren dar. Das Ziel dieser Studie war es festzustellen, ob der komplette Erhalt der subvalvulären Strukturen beim Mitralklappenersatz Vor- oder Nachteile hat. Es wird über die Erfahrungen mit 48 Patienten berichtet. Die Gruppe MKEh bestand aus 15 Patienten, bei denen beim MKE der komplette subvalvuläre Halteapparat erhalten wurde. Die Gruppe MKEo, bei denen beim MKE nur der posteriore Halteapparat erhalten wurde, bestand aus 9 Patienten. Die dritte Gruppe (MKR) enthielt 12 Patienten, bei denen die Mitralklappe rekonstruiert worden war und die vierte Gruppe (KG) bestand aus 12 Herzgesunden ohne Klappendefekt, die die Kontrollgruppe darstellte. Die Patienten wurden einer ausführlichen Befragung unterzogen sowie prä- und postoperativ echokardiographisch untersucht und die Ergebnisse verglichen. Bezüglich der Ergebnisse der Befragungen und der präoperativen echokardiographischen Ergebnisse fanden sich bei den drei operierten Gruppen (MKEh, MKEo, MKR) keine signifikanten Unterschiede. Demgegenüber wurden postoperative Unterschiede festgestellt: Bei den Patienten mit MKE, bei denen aber der vordere Halteapparat nicht konserviert wurde (MKEo), fand sich eine signifikant geringere systolische Verkürzung zwischen dem Apex und der Mitralklappenbasis (6,5 mm - 15 mm), die systolische Kontraktion begann bei diesen Patienten außerdem nicht im Bereich des Apex und der posteriore Papillarmuskel führte in diesen Fällen keine aktive Kontraktion aus. Es konnte somit die Schlußfolgerung gezogen werden, daß der komplette subvalvuläre Apparat notwendig ist, damit der linke Ventrikel eine physiologische Kontraktion durchführen kann. Er sollte somit immer beim Mitralklappenersatz komplett erhalten werden, sofern die Papillarmuskeln und die Chorden intakt sind und keine Mitralklappenrekonstruktion durchgeführt werden kann. / Today preservation of the chordal attachment to the posterior leaflet in mitral valve replacement (MVR) is a routine, universally accepted procedure. The aim of this study was to show the advantages and disadvantages of the preservation of the entire subvalvular structures. Our institution's experience with 48 patients in four groups is reported. The MKEh group consists of 15 patients who underwent MVR with preservation of the entire subvalvular structures. The MKEo group, treated with MVR and preservation of the posterior subvalvular structures only, consists of 9 patients. The third group (MVR) consists of 12 patients with mitral valve reconstruction and group 4 (CG) of 12 healthy individuals without heart valve dysfunction, as a control group. The patients were assessed by questioning and echocardiography pre- and postoperatively and the results compared. In questioning and in the preoperative echocardiography results no differences were seen between the three surgical groups (MKEh, MKEo, MKR). However, considerable differences were present in the postoperative echocardiography results: in patients without preservation of the anterior subvalvular structures (MKEo group) the shortening between the apex and the mitral valve basis is significantly less (6.5 mm - 15 mm), the systolic contraction does not begin at the apex and the posterior papillary muscle does not actively contract. It is concluded that preservation of the entire subvalvular structures is important to ensure physiological contraction of the left ventricle. They should be preserved in all mitral valve replacement operations when the papillary muscles und chordae are intact and mitral valve reconstruction cannot be performed.