Ziel: Die partielle Ventrikulektomie (PLV) stellt eine chirurgische Therapieoption der terminalen Herzinsuffizienz dar. In dieser Arbeit wurde der Einfluss der PLV auf die kardiale Leistungsfähigkeit untersucht sowie eine Überlebensanalyse durchgeführt. Ferner sollte eine Aussage zum Verhalten der postoperativen linksventrikulären Funktion unter Belastung gemacht werden. Dabei wurden zwei Gruppen miteinander verglichen: 1. Patienten mit idiopathischer Kardiomyopathie (Gruppe ID) und 2. Patienten mit ischämischer Myopathie (Gruppe IS). Material und Methodik: Insgesamt wurden 75 Patienten, die sich im Zeitraum von 1995 bis 1999 in der Klinik für kardiovaskuläre Chirurgie der Charité einer PLV unterzogen hatten, berücksichtigt. Die postoperativen Untersuchungen erfolgten an 19 Patienten. Die linksventrikulären Funktionsparameter wurden mittels transthorakaler und transösophagealer Echokardiographie einschließlich Stressechokardiographie erhoben. Ergebnisse: In beiden Gruppen war postoperativ eine hochsignifikante Verbesserung der NYHA-Klassifikation zu registrieren. Die echokardiographischen Untersuchungen ergaben in beiden Gruppen eine Verbesserung der Ejektionsfraktion (EF) als Maß für die linksventrikuläre Funktion. Ferner war eine Verringerung des linksventrikulären enddiastolischen Durchmessers (LVEDD) und ein signifikanter Rückgang der Mitralinsuffizienz (MI) festzustellen. Die Stressechokardiographie zeigte für die Gruppe IS eine Steigerung der Kontraktilität unter Dobutamin mit tendenziell physiologischen Befunden. (signifikanter Anstieg von EF, cardiac index (CI), fractional area change (FAC) sowie Abnahme des linksventrikulären endsystolischen Volumenindex (LVESVI)). Für die Gruppe ID konnte dies nur bedingt gezeigt werden. Bei der Überlebensanalyse ergaben sich ebenfalls ein signifikant besseres Abschneiden der Gruppe IS, insgesamt lag die Überlebensrate hinsichtlich kardialer Todesursachen bei 69,9 % (1. Jahr) und 66,7 % (2. Jahr). Schlussfolgerungen: Beurteilend lässt sich feststellen, dass die überlebenden und zur Nachuntersuchung erschienenen Patienten mit einer Steigerung der körperlichen Belastbarkeit und Besserung der Ventrikelfunktionsparameter von der Operation profitieren konnten, wobei sich ein besseres Abschneiden der Gruppe IS zeigte. Dazu passend wies auch die stressechokardiographische Untersuchung vor allem für die Gruppe IS postoperativ auf myokardiale Reserven hin. Die hier aufgezeigten Unterschiede der Gruppen, die sich auch in den Überlebensraten widerspiegeln, machen die Bedeutung von guten Selektionskriterien deutlich, die in weiteren Studien noch differenzierter betrachtet werden müssen. Damit zusammenhängend kommt auch der Anpassung der mit der PLV kombinierten Eingriffe an die Ursachen der Myopathien besondere Wichtigkeit zu. / Aim: Partial left ventriculectomy (PLV) represents a surgical option for the treatment of end-stage-heart failure. The aim of this thesis was an investigation of the influence of PLV on LV-function and on clinical outcome and to analyse survival in a group of patients submitted to PLV: Also, post surgical left ventricular function under stress conditions was determined. Two groups served as a basis for comparison: 1. patients with idiopathic dilated cardiomyopathy (ID group) and 2. patients with ischemic myopathy (IS group). Methods: 75 patients undergoing PLV at the clinic for cardiovascular surgery at the Charité Berlin between 1995 and 1999 were considered. LV-function was determined by transthoracic and transesophageal echocardiography including stress echocardiography. Results: The NYHA-classification improved in both groups significantly after the surgery. The echocardiography showed a significant increase in ejection fraction (EF), a reduction of left ventricular enddiastolic diameter (LVEDD) and a significant decrease in mitral insufficiency (MI). The post surgical stress-echocardiography indicated a rise of left ventricular contractility under dobutamine with a tendency to physiological results (significant increase in EF, cardiac index (CI), fractional area change (FAC) and decrease in left ventricular enddiastolic volume index (LVEDVI)) in the IS group. Concerning the ID group, these results were only partially valid. Looking at the survival rates it turned out that they are significantly higher for the IS group than for the ID group. All in all, 1-year-survival was at 69,9 % and 2-year-survival was at 66,7 %. Conclusion: It can be concluded that survivors profited from the surgery which is shown by the improvement of physical capacity and left ventricular parameters. This applies especially to patients from the IS group, which conforms to the fact that also the post surgical stress echocardiography revealed myocardial reserves for this group. The differences between the groups which have been demonstrated in these investigations and which are also reflected in survival rates stress the importance of carefully chosen selection criteria and the need for further subtly differentiated research in this special field. Considering this, also the correlation between the intervention combined with PLV and the cause of the myopathy is of great importance.

Fundamento: A artéria torácica interna (ATI) \"in situ\" apresenta predomínio de fluxo sistólico, mas após sua anastomose no sistema coronariano esquerdo torna-se um sistema híbrido com predomínio de fluxo diastólico, sendo a relevância da patência ou não dos grandes ramos proximais da ATI anastomosada controversa quanto à possibilidade de roubo de fluxo. Porém, constata-se que durante o ecocardiograma sob estresse com dobutamina (EED), o estado funcional da ATI anastomosada pode ser avaliado através da reserva coronariana, além da verificação dos distintos efeitos no fluxo sistólico (FS), diastólico (FD) e total (FT = sistólico + diastólico). Objetivo: Verificar por meio da ecocardiografia e Doppler o efeito dos ramos proximais importantes da ATI no fluxo, na reserva de velocidade (RVFC) e de fluxo (RFC) coronariano, em pacientes com fração de ejeção do ventrículo esquerdo (FEVE) preservada (> 50%). Métodos: Em ensaio clínico prospectivo controlado e randomizado, foram avaliados pacientes com (Grupo I) e sem (Grupo II), a ligadura dos ramos proximais importantes da ATI anastomosada na coronária descendente anterior. As avaliações das ATIs em nível supraclavicular e os ecocardiogramas transtorácicos foram realizados no pré-operatório, no pós-operatório precoce, seis meses após a cirurgia em condição basal e durante o EED. Neste, foi alcançada a frequência cardíaca submáxima [(220 - idade) x (0,85)] sem a ocorrência de isquemia no território subjacente à ATI anastomosada em todos os pacientes. Foram medidos o FS, o FD, o FT e o percentual de FD, nos quatro momentos do estudo. O percentual de FD resultou da divisão da integral da velocidade diastólica do fluxo pela integral da velocidade total (sistólica + diastólica) do fluxo. A reserva coronariana foi obtida através do Doppler da ATI anastomosada seis meses após a cirurgia, sendo calculada através da razão entre o valor da variável registrado no EED e em condição basal, utilizando-se para as RVFCs o pico e a média de velocidade diastólica, e para a RFC o FT. As distribuições das variáveis contínuas foram comparadas através do Teste t Student, quando as variáveis eram aproximadamente normais, ou através do Teste da Soma dos Postos de Wilcoxon (Mann-Whitney), quando as variáveis não eram aproximadamente normais. Proporções foram comparadas através do teste exato de Fisher. O valor-p < 0,05 entre os grupos foi considerado estatisticamente significativo. Resultados: O Grupo I (25 pacientes) e o Grupo II (28 pacientes) não foram diferentes quanto às características clínicas e ecocardiográficas, constatando-se a FEVE preservada em todos os casos. O FD não diferiu entre os grupos nos quatro momentos do estudo. Entretanto, verificou-se durante o EED que o FS (19,5 ± 9,3 ml/min vs. 32,7 ± 19,4 ml/min; p < 0,05) e o FT (79,1 ± 21,4 ml/min vs. 101,1 ± 47,4 ml/min; p < 0,05) foram maiores no Grupo II. Contudo, o percentual de FD foi maior no Grupo I (76,4 ± 12,7% vs. 68,9 ± 10%; p < 0,05) durante o EED, em virtude de o Grupo I apresentar menos componente sistólico. O percentual de FD < 50% ocorreu em todos os casos no pré - operatório, em cinco casos no pós - operatório precoce e em dez casos em condição basal seis meses após a cirurgia. Todavia, durante o EED, todos os casos apresentaram o percentual de FD > 50%, sendo este percentual de 100% em cinco casos (quatro no Grupo I). Os grupos não apresentaram diferença entre as RFCs (1,9 ± 0,46 vs. 2,11 ± 0,56; p = 0,143) ou as RVFCs calculadas com o pico (2,17 ± 0,64 vs.2,28 ± 0,63; p = 0,537) e com a média (2,27 ± 0,54 vs.2,50 ± 0,79; p= 0,232) da velocidade diastólica. Conclusão: Concluímos que o adequado estado funcional da ATI anastomosada independe da presença ou ausência dos importantes ramos proximais. Assim, a ligadura dos ramos não determina aumento do fluxo sistólico, diastólico ou total através deste enxerto, e o predomínio diastólico é mais evidente sob a condição estresse. O aumento dos fluxos sistólico e total indicam para a adaptação do fluxo através desta artéria para suprir a ambas, circulação coronariana e não coronariana, nos pacientes que não têm esses ramos ligados durante a cirurgia. Estes achados apontam para o entendimento de que a hipótese do roubo de fluxo pelos ramos não ligados é improvável / Background: The internal thoracic artery (ITA) \"in situ\" has systolic flow predominance, but when grafted to the left coronary artery system, the ITA becomes a hybrid system with diastolic flow predominance. The relevance of the patency or not-patency of the large proximal branches of the ITA graft is controversial in regards to the possibility of flow steal. During dobutamine stress echocardiography (DSE), the functional status of the ITA graft can be assessed by the coronary reserve in addition to assessment of the distinct effects of DSE on systolic (SF), diastolic (DF), and total flow (TF = systolic + diastolic). Objective: To assess, by Doppler echocardiography, the effects of the significant proximal branches of ITA graft in the flow, coronary flow velocity reserve (CFVR) and coronary flow reserve (CFR), in patients with preserved (> 50%) left ventricular ejection fraction (LVEF). Methods: In a prospective randomized controlled clinical trial we evaluate patients with (Group I) and without (Group II) ligation of important proximal branches of the ITA grafted to the anterior descending coronary artery. Supraclavicular assessment of the ITAs and transthoracic echocardiograms were performed, at rest and during DSE, on pre-operative, early and six months post-operative. In all patients, the submaximal heart rate [(220 - age) x (0.85)] was achieved during DSE with no ischemia to the area matching the ITA graft. The SF, DF, TF and percentage of DF were measured in the four moments of this study. The percentage of DF was calculated by the ratio of the integral of the diastolic flow velocity by the integral of the total flow velocity (systolic + diastolic). The coronary reserve was assessed at six months post-operative, and it was calculated by the ratio of the variable during DSE and at rest, using the maximum and the mean of the diastolic flow velocity to calculate the CFVR; and the TF to calculate the CFR. Student\'s t-tests or Wilcoxon\'s rank sum test (Mann-Whitney) were used to examine differences between the groups in normally distributed or not-normally-distributed continuous variables, respectively. Fisher exact test was used to examine the difference in proportions. A p value < 0.05 was considered statistically significant. Results: Group I (25 patients) and Group II (28 patients) were not different regarding to clinical and echocardiographic characteristics, with preservation of the LVEF in all cases. The DF was not different between the groups in the four moments of this study. However, during the DSE, the SF (19.5 ± 9.3 ml/min vs. 32.7 ± 19.4 ml/min, p < 0.05) and TF (79.1 ± 21.4 ml/min vs. 101 1 ± 47.4 ml/min; p < 0.05) were higher in Group II. On the other hand, during the DSE, the percentage of DF was higher in Group I (76.4 ± 12.7% vs. 68.9 ± 10%; p < 0.05), due to its lower systolic component. The percentage of DF < 50% occurred in all cases in the pre-operative, in five cases in the early post-operative and in ten cases, at rest, six months postoperatively. However, during the DSE, all cases showed the percentage of DF > 50%, furthermore five cases (four in Group I) had the percentage of DF of 100%. There was no difference between the groups in regards to CFR (1.9 ± 0.46 vs. 2.11 ± 0.56; p = 0.143), or CFVR calculated using the maximum (2.17 ± 0.64 vs. 2.28 ± 0.63; p = 0.537) and the mean (2.27 ± 0.54 vs. 2.50 ± 0.79; p = 0.232) of the diastolic velocity. Conclusion: The appropriate functional status of the ITA graft does not depend on the ligation or preservation of important proximal ITA branches. Thus, ligation of ITA branches does not determine increase in systolic, diastolic or total flow through the ITA graft, and its diastolic predominance is more evident under stress. The increase in the systolic and total flow indicates an adaptation of the flow through the ITA graft to supply both coronary and non-coronary systems, in those patients that don\'t have the branches ligated during surgery. These findings point towards the hypothesis that the flow steal by unligated branches is unlikely.

Fundamento: A artéria torácica interna (ATI) \"in situ\" apresenta predomínio de fluxo sistólico, mas após sua anastomose no sistema coronariano esquerdo torna-se um sistema híbrido com predomínio de fluxo diastólico, sendo a relevância da patência ou não dos grandes ramos proximais da ATI anastomosada controversa quanto à possibilidade de roubo de fluxo. Porém, constata-se que durante o ecocardiograma sob estresse com dobutamina (EED), o estado funcional da ATI anastomosada pode ser avaliado através da reserva coronariana, além da verificação dos distintos efeitos no fluxo sistólico (FS), diastólico (FD) e total (FT = sistólico + diastólico). Objetivo: Verificar por meio da ecocardiografia e Doppler o efeito dos ramos proximais importantes da ATI no fluxo, na reserva de velocidade (RVFC) e de fluxo (RFC) coronariano, em pacientes com fração de ejeção do ventrículo esquerdo (FEVE) preservada (> 50%). Métodos: Em ensaio clínico prospectivo controlado e randomizado, foram avaliados pacientes com (Grupo I) e sem (Grupo II), a ligadura dos ramos proximais importantes da ATI anastomosada na coronária descendente anterior. As avaliações das ATIs em nível supraclavicular e os ecocardiogramas transtorácicos foram realizados no pré-operatório, no pós-operatório precoce, seis meses após a cirurgia em condição basal e durante o EED. Neste, foi alcançada a frequência cardíaca submáxima [(220 - idade) x (0,85)] sem a ocorrência de isquemia no território subjacente à ATI anastomosada em todos os pacientes. Foram medidos o FS, o FD, o FT e o percentual de FD, nos quatro momentos do estudo. O percentual de FD resultou da divisão da integral da velocidade diastólica do fluxo pela integral da velocidade total (sistólica + diastólica) do fluxo. A reserva coronariana foi obtida através do Doppler da ATI anastomosada seis meses após a cirurgia, sendo calculada através da razão entre o valor da variável registrado no EED e em condição basal, utilizando-se para as RVFCs o pico e a média de velocidade diastólica, e para a RFC o FT. As distribuições das variáveis contínuas foram comparadas através do Teste t Student, quando as variáveis eram aproximadamente normais, ou através do Teste da Soma dos Postos de Wilcoxon (Mann-Whitney), quando as variáveis não eram aproximadamente normais. Proporções foram comparadas através do teste exato de Fisher. O valor-p < 0,05 entre os grupos foi considerado estatisticamente significativo. Resultados: O Grupo I (25 pacientes) e o Grupo II (28 pacientes) não foram diferentes quanto às características clínicas e ecocardiográficas, constatando-se a FEVE preservada em todos os casos. O FD não diferiu entre os grupos nos quatro momentos do estudo. Entretanto, verificou-se durante o EED que o FS (19,5 ± 9,3 ml/min vs. 32,7 ± 19,4 ml/min; p < 0,05) e o FT (79,1 ± 21,4 ml/min vs. 101,1 ± 47,4 ml/min; p < 0,05) foram maiores no Grupo II. Contudo, o percentual de FD foi maior no Grupo I (76,4 ± 12,7% vs. 68,9 ± 10%; p < 0,05) durante o EED, em virtude de o Grupo I apresentar menos componente sistólico. O percentual de FD < 50% ocorreu em todos os casos no pré - operatório, em cinco casos no pós - operatório precoce e em dez casos em condição basal seis meses após a cirurgia. Todavia, durante o EED, todos os casos apresentaram o percentual de FD > 50%, sendo este percentual de 100% em cinco casos (quatro no Grupo I). Os grupos não apresentaram diferença entre as RFCs (1,9 ± 0,46 vs. 2,11 ± 0,56; p = 0,143) ou as RVFCs calculadas com o pico (2,17 ± 0,64 vs.2,28 ± 0,63; p = 0,537) e com a média (2,27 ± 0,54 vs.2,50 ± 0,79; p= 0,232) da velocidade diastólica. Conclusão: Concluímos que o adequado estado funcional da ATI anastomosada independe da presença ou ausência dos importantes ramos proximais. Assim, a ligadura dos ramos não determina aumento do fluxo sistólico, diastólico ou total através deste enxerto, e o predomínio diastólico é mais evidente sob a condição estresse. O aumento dos fluxos sistólico e total indicam para a adaptação do fluxo através desta artéria para suprir a ambas, circulação coronariana e não coronariana, nos pacientes que não têm esses ramos ligados durante a cirurgia. Estes achados apontam para o entendimento de que a hipótese do roubo de fluxo pelos ramos não ligados é improvável / Background: The internal thoracic artery (ITA) \"in situ\" has systolic flow predominance, but when grafted to the left coronary artery system, the ITA becomes a hybrid system with diastolic flow predominance. The relevance of the patency or not-patency of the large proximal branches of the ITA graft is controversial in regards to the possibility of flow steal. During dobutamine stress echocardiography (DSE), the functional status of the ITA graft can be assessed by the coronary reserve in addition to assessment of the distinct effects of DSE on systolic (SF), diastolic (DF), and total flow (TF = systolic + diastolic). Objective: To assess, by Doppler echocardiography, the effects of the significant proximal branches of ITA graft in the flow, coronary flow velocity reserve (CFVR) and coronary flow reserve (CFR), in patients with preserved (> 50%) left ventricular ejection fraction (LVEF). Methods: In a prospective randomized controlled clinical trial we evaluate patients with (Group I) and without (Group II) ligation of important proximal branches of the ITA grafted to the anterior descending coronary artery. Supraclavicular assessment of the ITAs and transthoracic echocardiograms were performed, at rest and during DSE, on pre-operative, early and six months post-operative. In all patients, the submaximal heart rate [(220 - age) x (0.85)] was achieved during DSE with no ischemia to the area matching the ITA graft. The SF, DF, TF and percentage of DF were measured in the four moments of this study. The percentage of DF was calculated by the ratio of the integral of the diastolic flow velocity by the integral of the total flow velocity (systolic + diastolic). The coronary reserve was assessed at six months post-operative, and it was calculated by the ratio of the variable during DSE and at rest, using the maximum and the mean of the diastolic flow velocity to calculate the CFVR; and the TF to calculate the CFR. Student\'s t-tests or Wilcoxon\'s rank sum test (Mann-Whitney) were used to examine differences between the groups in normally distributed or not-normally-distributed continuous variables, respectively. Fisher exact test was used to examine the difference in proportions. A p value < 0.05 was considered statistically significant. Results: Group I (25 patients) and Group II (28 patients) were not different regarding to clinical and echocardiographic characteristics, with preservation of the LVEF in all cases. The DF was not different between the groups in the four moments of this study. However, during the DSE, the SF (19.5 ± 9.3 ml/min vs. 32.7 ± 19.4 ml/min, p < 0.05) and TF (79.1 ± 21.4 ml/min vs. 101 1 ± 47.4 ml/min; p < 0.05) were higher in Group II. On the other hand, during the DSE, the percentage of DF was higher in Group I (76.4 ± 12.7% vs. 68.9 ± 10%; p < 0.05), due to its lower systolic component. The percentage of DF < 50% occurred in all cases in the pre-operative, in five cases in the early post-operative and in ten cases, at rest, six months postoperatively. However, during the DSE, all cases showed the percentage of DF > 50%, furthermore five cases (four in Group I) had the percentage of DF of 100%. There was no difference between the groups in regards to CFR (1.9 ± 0.46 vs. 2.11 ± 0.56; p = 0.143), or CFVR calculated using the maximum (2.17 ± 0.64 vs. 2.28 ± 0.63; p = 0.537) and the mean (2.27 ± 0.54 vs. 2.50 ± 0.79; p = 0.232) of the diastolic velocity. Conclusion: The appropriate functional status of the ITA graft does not depend on the ligation or preservation of important proximal ITA branches. Thus, ligation of ITA branches does not determine increase in systolic, diastolic or total flow through the ITA graft, and its diastolic predominance is more evident under stress. The increase in the systolic and total flow indicates an adaptation of the flow through the ITA graft to supply both coronary and non-coronary systems, in those patients that don\'t have the branches ligated during surgery. These findings point towards the hypothesis that the flow steal by unligated branches is unlikely.

No description available.

Le diabète est aujourd’hui la 7ème cause de mortalité dans le monde. Dans cette population, la cardiomyopathie diabétique est la principale cause de morbi-mortalité. Le développement de cette complication débutant dès l’apparition du diabète, un dépistage et une prise en charge précoces de cette pathologie sont donc de première importance et sont les deux objectifs visés par ces travaux. La première étude que nous avons réalisée a permis de démontrer l’utilité d’une évaluation compréhensive de la fonction régionale myocardique gauche par 2D speckle-tracking imaging, en conditions de stress à la dobutamine, dans le dépistage précoce de la cardiomyopathie diabétique chez des patients diabétiques de type 2 asymptomatiques. La deuxième partie de ces travaux a, quant à elle, donné lieu à deux études. L’étude clinique a permis de mettre en évidence une amélioration de la réponse au stress de la fonction régionale myocardique après 3 mois de supplémentation en vitamine D3 chez des patients carencés. L’étude expérimentale a, pour sa part, souligné les effets bénéfiques sur le remodelage et la fonction cardiaques de cette supplémentation, en prévention secondaire, dans un modèle murin de diabète de type 2 induit par un régime gras et sucré. Par ailleurs, cette étude a mis en lumière l’implication potentielle d’une modulation des taux myocardiques en espèces lipotoxiques par la vitamine D3 dans ces effets. L’ensemble de ces travaux de thèse a ainsi permis, d’une part, de proposer une technique de dépistage des signes précoces d’altération de la fonction cardiaque chez le patient diabétique de type 2 et, d’autre part, de montrer les effets bénéfiques d’une supplémentation en vitamine D3 dans ce contexte. / Diabetes has reached the 7th place in the world’s top ten mortality causes. In this population, morbi-mortality mainly originates from diabetic cardiomyopathy. This complication evolving from the onset of diabetes, early diagnosis and care are of paramount importance and are the two purposes of this work. In our first study, we demonstrated the relevance of a comprehensive 2D speckle-tracking imaging analysis, under dobutamine stress, in unmasking early left ventricular regional myocardial dysfunction in a population of asymptomatic type 2 diabetic patients. In the second part of this work, we performed two studies. In the first one, we brought to light an improvement of regional myocardial function response to dobutamine stress after a three-month vitamin D3 supplementation protocol, in deficient patients. The second study was performed in a mouse model of diet-induced type 2 diabetes. In this last work, we put forward the beneficial effects of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function. These cardioprotective effects may be, at least in part, on account of modulatory effects of vitamin D3 on myocardial lipotoxic species levels. This whole work allow us to propose a tool enabling recognition of early cardiac function impairments in type 2 diabetic patients and to demonstrate the beneficial effects of vitamin D3 supplementation in this context.